Adrian Hobbs

Adrian Hobbs

Professor of Cardiovascular Pharmacology

I completed my B.Sc. in Pharmacology, obtaining First Class Honours, at King’s College London in 1989 and remained at the same institution to undertake a Ph.D. with Dr. Alan Gibson in the Pharmacology Department. During my Ph.D. research I made a significant contribution to the understanding of the role of nitric oxide (NO) as a neurotransmitter in non-adrenergic, non-cholinergic (NANC) nerves, using the rodent anococcygeus as a classical model of nitrergic innervation. I was also the first to demonstrate the importance of NO-mediated NANC transmission in regulating airway smooth muscle tone.
Having completed my Ph.D. in the autumn of 1992, I took up a post-doctoral position in the laboratory of Nobel Laureate, Prof. L.J. Ignarro, in the Department of Pharmacology at the University of California, Los Angeles. My first two years at UCLA were supported by a Fulbright-Hays Research Fellowship and subsequently I was awarded a Fellowship by the American Heart Association to remain in Prof. Ignarro’s lab for a further two years. During this time, my attention turned to NO synthase itself and the biochemical mechanisms regulating enzyme activity. In particular, I focused on the bioactivity of nitroxyl (HNO) and provided the first convincing evidence that this molecule can be generated endogenously (by NO synthase). The significance of HNO to human physiology and pathophysiology is now at the very cutting edge of NO research, as it relates to host defence & cardiac function.
At the end of 1996, I returned to the UK to take up a post-doctoral position at the Wolfson Institute for Biomedical Research, University College London, under the mentorship of Sir Salvador Moncada. Since that time I have established my own independent research group with extensive peer reviewed support from the Wellcome Trust, BHF and BBSRC; as well as securing my own personal funding, initially being awarded a Wellcome Trust Career Development Fellowship and later a Wellcome Trust Senior Fellowship. Since returning from the US, my group has focused on the guanylate cyclase family of enzymes and the interaction between NO and natriuretic peptides in the cardiovascular system. This area of interest has taken my research into the realm of pulmonary hypertension and potentially new therapeutic approaches for this debilitating disease (schematic).
More recently, I have initiated a programme of work that has culminated in the identification of C-type natriuretic peptide as an important endothelium-derived vasoactive peptide; in addition, I have discovered and characterised a novel signalling pathway in the blood vessel wall, triggered by CNP, involving activation of natriuretic peptide receptor-C (NPR-C) and G-protein gated inwardly-rectifying K+ channels (GIRKs) that regulating vascular tone, local blood flow and systemic blood pressure (schematic).
Within the Heart Centre at the WHRI, as Professor of Cardiovascular Pharmacology I aim to harness the translational potential of the environment, exploiting the exceptional links between pre-clinical and clinical research, with the goal of developing and evaluating novel treatments for cardiovascular disease stemming from my academic research findings; this will centre on ischaemic disorders (myocardial infarction, stroke) and pulmonary hypertension/heart failure.

Summary of Research

The focus of our research is the physiological and pathological actions and interactions of a family of homologous enzymes, the guanylate cyclases (GC), with emphasis on the cardiovascular system. These proteins act as receptors for nitric oxide (NO) and natriuretic peptides and exert complementary cytoprotective, anti-atherosclerotic effects on the heart and vasculature. In accord, loss of these signalling pathways precipitates cardiovascular disease.
My group possesses diverse expertise and employs a multi-disciplinary, molecule-to-man approach including cell and molecular biology, biochemistry, in vitro & in vivo pharmacology (including several transgenics and models of disease), and clinical studies in healthy volunteers and patients, to investigate the significance of these enzymes in health and disease. The translational aspects of my work are highlighted by our ‘drug development’ programmes that are approaching, or currently undergoing, clinical evaluation.

  • My major research efforts include:
    Pharmacological and biochemical characterization of the mechanism of sGC activation by NO-donor drugs, non NO-based enzyme activators, nitroxyl (HNO), carbon monoxide (CO) and hydrogen sulphide (H2S)
  • Pharmacological assessment of the interaction between soluble and particulate isoforms of GC in the vasculature, in the context of pulmonary hypertension, heart failure and stroke; development of a novel combination therapy for pulmonary hypertension
  • Evaluation of the (patho)physiological roles of CNP as a mammalian endothelium-derived hyperpolarising factor (EDHF) in regulating vascular tone and blood flow
  • Investigation of the biological roles of the natriuretic peptide receptor (NPR)-C in regulating vascular smooth muscle, leukocyte and platelet reactivity; design & development of small molecule NPR-C agonists for the treatment of cardiovascular disease.

Key Publications

(* Denotes equal contribution and # corresponding author)
* Baliga, R.S., Milsom, A.B., Ghosh, S.M., Trinder, S.L., MacAllister, R.J., Ahluwalia, A.* & Hobbs, A.J.*# (2012). Dietary nitrate ameliorates pulmonary hypertension: cytoprotective role for endothelial nitric oxide synthase and xanthine oxidoreductase. Circulation, 25, 2922-32.

* Villar, I.C., Scotland, R.S., Khambata, R.S., Chan, M., Duchene, J., Sampaio, A.L., Perretti, M., Ahluwalia, A.*# & Hobbs, A.J.* (2011). Suppression of endothelial P-selectin expression contributes to reduced cell trafficking in females: an effect independent of NO and prostacyclin. Arterioscler Thromb Vasc Biol., 31, 1075-83.

* Baliga, R.S., Zhao, L., Madhani, M., Lopez-Torondel, B., Visintin, C., Selwood, D., Wilkins, M.R., MacAllister, R.J. & Hobbs, A.J.# (2008). Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension. Am. J. Respir. Crit. Care Med., 178, 861-9.

* Marro, M.L., Peiró, C., Panayiotou, C.M., Baliga, R.S., Meurer, S., Schmidt, H.H. & Hobbs, A.J.# (2008). Characterization of the human alpha1 beta1 soluble guanylyl cyclase promoter: key role for NF-kappaB(p50) and CCAAT-binding factors in regulating expression of the nitric oxide receptor. J. Biol. Chem., 283, 20027-36.

* Villar, I.C., Panayiotou, C.M., Sheraz, A., Madhani, M., Scotland, R.S., Nobles, M., Kemp-Harper, B., Ahluwalia, A. & Hobbs, A.J.# (2007). Definitive role for natriuretic peptide receptor-C in mediating the vasorelaxant activity of C-type natriuretic peptide and endothelium-derived hyperpolarising factor. Cardiovasc. Res., 74, 515-525.

* Scotland, R.S., Cohen, M., Foster, P., Lovell, M., Mathur, A., Ahluwalia, A. & Hobbs, A.J.# (2005). C-type natriuretic peptide (CNP) inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression. Proc. Natl. Acad. Sci. USA., 102, 14452-14457.

* Ahluwalia, A., Foster, P., Scotland, R.S., McLean, P.G., Mathur, A., Perretti, M., Moncada, S. & Hobbs, A.J.# (2004). Anti-inflammatory activity of soluble guanylate cyclase: cGMP-dependent down-regulation of P-selectin expression and leukocyte recruitment. Proc. Natl. Acad. Sci. USA., 101, 1386-1391.

* Hobbs, A.J.#, Foster, P., Prescott, C., Scotland, R. & Ahluwalia, A. (2004). Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for endothelium-derived C-type natriuretic peptide. Circulation, 110, 1231-1235.

* Chauhan, S.D., Nilsson, H., Ahluwalia, A. & Hobbs, A.J.# (2003). Release of C-type natriuretic peptide accounts for the biological activity of endothelium-derived hyperpolarizing factor. Proc. Natl. Acad. Sci. USA., 100, 1426-1431.

* Connelly, L., Palacios-Callender, M., Ameixa, C., Moncada, S. & Hobbs A.J.# (2001). Biphasic regulation of NF-κB activity underlies the pro- and anti- inflammatory actions of nitric oxide. J. Immunol., 166, 3873-3881.

PubLists Publications

Derrett-Smith EC, Dooley A, Gilbane AJ et al. (2013). Endothelial Injury in a Transforming Growth Factor β-Dependent Mouse Model of Scleroderma Induces Pulmonary Arterial Hypertension.. Arthritis Rheum Vol.65, (11) 2928-2939.
10.1002/art.38078
Sciarretta S, Marchitti S, Bianchi F et al. (2013). C2238 Atrial Natriuretic Peptide Molecular Variant Is Associated With Endothelial Damage and Dysfunction Through Natriuretic Peptide Receptor C Signaling. CIRCULATION RESEARCH Vol.112, (10) 0009-7330 1355-+.
10.1161/CIRCRESAHA.113.301325
Ghosh SM, Kapil V, Fuentes-Calvo I et al. (2013). Enhanced vasodilator activity of nitrite in hypertension: critical role for erythrocytic xanthine oxidoreductase and translational potential.. Hypertension Vol.61, (5) 1091-1102.
10.1161/HYPERTENSIONAHA.111.00933
Ahluwalia A, Hobbs AJ (2013). Letter by Ahluwalia and Hobbs Regarding Article, "Nitrate-Nitrite-Nitric Oxide Pathway in Pulmonary Arterial Hypertension Therapeutics". CIRCULATION Vol.127, (2) 0009-7322 E275-E275.
10.1161/CIRCULATIONAHA.112.118356
Peake N, Su N, Ramachandran M et al. (2013). Natriuretic peptide receptors regulate cytoprotective effects in an ex vivo human 3D / bioreactor model. Arthritis Research and Therapy Vol., () -.
10.1186/ar4253
Baliga RS, Macallister RJ, Hobbs AJ (2013). Vasoactive peptides and the pathogenesis of pulmonary hypertension: role and potential therapeutic application.. Handb Exp Pharmacol Vol.218, () 0171-2004 477-511.
10.1007/978-3-642-38664-0_19
Chan MV, Bubb KJ, Noyce A et al. (2012). Distinct endothelial pathways underlie sexual dimorphism in vascular auto-regulation.. Br J Pharmacol Vol.167, (4) 805-817.
10.1111/j.1476-5381.2012.02012.x
Baliga RS, Milsom AB, Ghosh SM et al. (2012). Dietary nitrate ameliorates pulmonary hypertension: cytoprotective role for endothelial nitric oxide synthase and xanthine oxidoreductase.. Circulation Vol.125, (23) 2922-2932.
10.1161/CIRCULATIONAHA.112.100586
Derrett-Smith E, Dooley A, Baliga R et al. (2012). SYSTEMIC VEGF INHIBITION INDUCES PULMONARY ARTERIAL HYPERTENSION IN A TRANSGENIC MOUSE MODEL OF SCLERODERMA. RHEUMATOLOGY Vol.51, () 1462-0324 41-41.
Gonzalez MA, Yim MA, Cheng S et al. (2012). Manganese Carbonyls Bearing Tripodal Polypyridine Ligands as Photoactive Carbon Monoxide-Releasing Molecules. INORGANIC CHEMISTRY Vol.51, (1) 0020-1669 601-608.
10.1021/ic2021287
Derrett-Smith E, Dooley A, Baliga R et al. (2011). Intermittent Systemic VEGF Inhibition Induces Pulmonary Arterial Hypertension In a Transgenic Mouse Model of Scleroderma. ARTHRITIS AND RHEUMATISM Vol.63, (10) 0004-3591 S1022-S1023.
Khambata RS, Panayiotou CM, Hobbs AJ (2011). Natriuretic peptide receptor-3 underpins the disparate regulation of endothelial and vascular smooth muscle cell proliferation by C-type natriuretic peptide.. Br J Pharmacol Vol.164, (2b) 584-597.
10.1111/j.1476-5381.2011.01400.x
Pourcet B, Feig JE, Vengrenyuk Y et al. (2011). LXRα regulates macrophage arginase 1 through PU.1 and interferon regulatory factor 8.. Circ Res Vol.109, (5) 492-501.
10.1161/CIRCRESAHA.111.241810
Velmurugan S, Kapil V, McKnight AHO et al. (2011). Dietary nitrate attenuates platelet reactivity: Role of the erythrocyte and influence of sex. NITRIC OXIDE-BIOLOGY AND CHEMISTRY Vol.24, () 1089-8603 S35-S36.
10.1016/j.niox.2011.03.285
Baliga RS, MacAllister RJ, Hobbs AJ (2011). New perspectives for the treatment of pulmonary hypertension.. Br J Pharmacol Vol.163, (1) 125-140.
10.1111/j.1476-5381.2010.01164.x
Villar IC, Scotland RS, Khambata RS et al. (2011). Suppression of endothelial P-selectin expression contributes to reduced cell trafficking in females: an effect independent of NO and prostacyclin.. Arterioscler Thromb Vasc Biol Vol.31, (5) 1075-1083.
10.1161/ATVBAHA.111.223545
Gonzalez MA, Fry NL, Burt R et al. (2011). Designed Iron Carbonyls as Carbon Monoxide (CO) Releasing Molecules: Rapid CO Release and Delivery to Myoglobin in Aqueous Buffer, and Vasorelaxation of Mouse Aorta. INORG CHEM Vol.50, (7) 0020-1669 3127-3134.
10.1021/ic2000848
Derrett-Smith EC, Dooley A, Baliga R et al. (2011). AN EXPLORATION OF PULMONARY VASCULAR VEGF SIGNALLING IN A TGF beta-DEPENDENT MOUSE MODEL OF SYSTEMIC SCLEROSIS. RHEUMATOLOGY Vol.50, () 1462-0324 134-135.
Kapil V, Benjamin N, Hobbs A et al. (2011). Response to Inorganic Nitrate for Blood Pressure Lowering?. HYPERTENSION Vol.57, (2) 0194-911X E3-E3.
10.1161/HYPERTENSIONAHA.110.164814
Derrett-Smith EC, Dooley A, Baliga R et al. (2010). Perturbed VEGF signalling within the pulmonary vasculature of a TGF beta dependent mouse model of systemic sclerosis. CLIN EXP RHEUMATOL Vol.28, (5) 0392-856X S63-S63.
Madhani M, Hall AR, Cuello F et al. (2010). Phospholemman Ser69 phosphorylation contributes to sildenafil-induced cardioprotection against reperfusion injury. AM J PHYSIOL-HEART C Vol.299, (3) 0363-6135 H827-H836.
10.1152/ajpheart.00129.2010
Kapil V, Milsom AB, Okorie M et al. (2010). Inorganic nitrate supplementation lowers blood pressure in humans: role for nitrite-derived NO.. Hypertension Vol.56, (2) 274-281.
10.1161/HYPERTENSIONAHA.110.153536
Kapil V, Maleki-Toyserkani S, Rehman F et al. (2010). Oral inorganic nitrate lowers blood pressure in healthy male, but not female, volunteers, via bioconversion to nitrite. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY Vol.70, (2) 0306-5251 285-285.
Panayiotou CM, Baliga R, Stidwill R et al. (2010). Resistance to endotoxic shock in mice lacking natriuretic peptide receptor-A.. Br J Pharmacol Vol.160, (8) 2045-2054.
10.1111/j.1476-5381.2010.00830.x
Khambata RS, Panayiotou CM, Xiao F et al. (2010). The anti-atherogenic potential of C-type natriuretic peptide: Disparate regulation of endothelial and vascular smooth muscle cell proliferation via natriuretic peptide receptor-C. FASEB JOURNAL Vol.24, () 0892-6638 -.
Milsom AB, Patel NSA, Mazzon E et al. (2010). Role for endothelial nitric oxide synthase in nitrite-induced protection against renal ischemia-reperfusion injury in mice. NITRIC OXIDE-BIOL CH Vol.22, (2) 1089-8603 141-148.
10.1016/j.niox.2009.10.010
Lumsden NG, Khambata RS, Hobbs AJ (2010). C-type Natriuretic Peptide (CNP): Cardiovascular Roles and Potential as a Therapeutic Target. CURR PHARM DESIGN Vol.16, (37) 1381-6128 4080-4088.
Lumsden NG, Khambata RS, Hobbs AJ (2010). C-type natriuretic peptide (CNP): cardiovascular roles and potential as a therapeutic target.. Curr Pharm Des Vol.16, (37) 4080-4088.
Duchene J, Cayla C, Vessillier S et al. (2009). Laminar shear stress regulates endothelial kinin B1 receptor expression and function: potential implication in atherogenesis.. Arterioscler Thromb Vasc Biol Vol.29, (11) 1757-1763.
10.1161/ATVBAHA.109.191775
Miller TW, Cherney MM, Lee AJ et al. (2009). The Effects of Nitroxyl (HNO) on Soluble Guanylate Cyclase Activity INTERACTIONS AT FERROUS HEME AND CYSTEINE THIOLS. J BIOL CHEM Vol.284, (33) 0021-9258 21788-21796.
10.1074/jbc.M109.014282
Kapil V, Rehman F, Arghandawi S et al. (2009). BLOOD PRESSURE LOWERING EFFECTS OF ORAL INORGANIC NITRATE VIA BIOCONVERSION TO NITRITE. BASIC CLIN PHARMACOL Vol.105, () 1742-7835 31-31.
Morris T, Stables M, Hobbs A et al. (2009). Effects of Low-Dose Aspirin on Acute Inflammatory Responses in Humans. J IMMUNOL Vol.183, (3) 0022-1767 2089-2096.
10.4049/jimmunol.0900477
Okorie M, Akram F, Loukogeorgakis S et al. (2009). ORAL INORGANIC NITRATE PROTECTS AGAINST ENDOTHELIAL ISCHAEMIA-REPERFUSION INJURY IN HUMANS. BASIC CLIN PHARMACOL Vol.105, () 1742-7835 26-26.
Kapil V, Okorie M, Akram F et al. (2009). Oral inorganic nitrate lowers blood pressure and protects against endothelial ischaemia-reperfusion injury in humans. NITRIC OXIDE-BIOLOGY AND CHEMISTRY Vol.20, () 1089-8603 S37-S37.
Milsom A, Patel N, Storey A et al. (2009). Role for endothelial nitric oxide synthase in nitrite-induced protection against renal ischaemia-reperfusion injury in mice. NITRIC OXIDE-BIOLOGY AND CHEMISTRY Vol.20, () 1089-8603 S39-S40.
10.1016/j.niox.2009.10.010
Hobbs AJ, Gane P, Lumsden N et al. (2009). Design and development of novel non-peptide agonists at natriuretic peptide receptor-C. FASEB JOURNAL Vol.23, () 0892-6638 -.
Hajihosseini MK, Ramasamy S, De Langhe S et al. (2009). Involvement of Fibroblast growth factor 10 (Fgf10) in the anterior-posterior patterning and specification of muscle and tendon progenitors in the developing mouse limbs. FASEB JOURNAL Vol.23, () 0892-6638 -.
Diller GP, Bedard E, Wort SJ et al. (2009). Response to Letter Regarding Article, "Circulating Endothelial Progenitor Cells in Patients With Eisenmenger Syndrome and Idiopathic Pulmonary Arterial Hypertension". CIRCULATION Vol.119, (9) 0009-7322 E231-E231.
10.1161/CIRCULATIONAHA.108.816363
Webb AJ, Milsom AB, Rathod KS et al. (2008). Mechanisms underlying erythrocyte and endothelial nitrite reduction to nitric oxide in hypoxia: role for xanthine oxidoreductase and endothelial nitric oxide synthase.. Circ Res Vol.103, (9) 957-964.
10.1161/CIRCRESAHA.108.175810
Baliga RS, Zhao L, Madhani M et al. (2008). Synergy between natriuretic peptides and phosphodiesterase 5 inhibitors ameliorates pulmonary arterial hypertension.. Am J Respir Crit Care Med Vol.178, (8) 861-869.
10.1164/rccm.200801-121OC
Marro ML, Peiro C, Panayiotou CM et al. (2008). Characterization of the human alpha(1)beta(1) soluble guanylyl cyclase promoter - Key role for NF-kappa B(p50) and CCAAT-binding factors in regulating expression of the nitric oxide receptor. J BIOL CHEM Vol.283, (29) 0021-9258 20027-20036.
10.1074/jbc.M801223200
Diller GP, van Eijl S, Okonko DO et al. (2008). Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. CIRCULATION Vol.117, (23) 0009-7322 3020-3030.
10.1161/CIRCULATIONAHA.108.769646
Chan MV, Hobbs AJ, Scotland RS et al. (2008). Nitric oxide-induced relaxation in female resistance arteries is endothelium-dependent. BASIC CLIN PHARMACOL Vol.102, () 1742-7835 38-38.
Villar IC, Hobbs AJ, Ahluwalia A (2008). Sex differences in vascular function: implication of endothelium-derived hyperpolarizing factor. J ENDOCRINOL Vol.197, (3) 0022-0795 447-462.
10.1677/JOE-08-0070
Aboud Z, Misra S, Warner T et al. (2008). The enterosalivary bioconversion of nitrate to nitrite underlies the blood pressure (BP) lowering and anti-platelet effects of a dietary nitrate load. BRITISH JOURNAL OF CLINICAL PHARMACOLOGY Vol.65, (6) 0306-5251 999-999.
Morton J, Coles B, Wright K et al. (2008). Circulating neutrophils maintain physiological blood pressure by suppressing bacteria and IFN gamma-dependent iNOS expression in the vasculature of healthy mice. BLOOD Vol.111, (10) 0006-4971 5187-5194.
10.1182/blood-2007-10-117283
Webb A, Patel N, Loukogeorgakis S et al. (2008). Acute blood pressure lowering and vasoprotective effects of dietary nitrate. FASEB JOURNAL Vol.22, () 0892-6638 -.
Panayiotou CM, Stidwill R, Taylor V et al. (2008). Resistance to endotoxic shock in mice lacking natriuretic peptide receptor-A. FASEB JOURNAL Vol.22, () 0892-6638 -.
Webb AJ, Patel N, Loukogeorgakis S et al. (2008). Acute blood pressure lowering, vasoprotective, and antiplatelet properties of dietary nitrate via bioconversion to nitrite. HYPERTENSION Vol.51, (3) 0194-911X 784-790.
10.1161/HYPERTENSIONAHA.107.103523
Milsom AB, Hobbs AJ, Ahluwalia A (2008). Endothelial nitric oxide synthase acts as a nitrite reductase in human endotheliall cells. NITRIC OXIDE-BIOLOGY AND CHEMISTRY Vol.19, () 1089-8603 S51-S52.
10.1016/j.niox.2008.06.134
Baliga R, Zhao L, Wilkins MR et al. (2007). Selective modulation of ANP-dependent dilation in the pulmonary vasculature by PDE 5 inhibitors: A novel combination therapy for pulmonary hypertension?. CIRCULATION Vol.116, (16) 0009-7322 456-456.
Webb AJ, Patel N, Loukogeorgakis S et al. (2007). Acute blood pressure (BP) lowering and vasoprotective effects of beetroot juice: relationship to nitrite derived from dietary nitrate. J HUM HYPERTENS Vol.21, (10) 0950-9240 834-835.
Webb AJ, Patel N, Loukogeorgakis S et al. (2007). Acute blood pressure lowering and vasoprotective effects of beetroot juice: relationship to nitrite derived from dietary nitrate. EUROPEAN HEART JOURNAL Vol.28, () 0195-668X 865-866.
Villar IC, Panayiotou CM, Sheraz A et al. (2007). Definitive role for natriuretic peptide receptor-C in mediating the vasorelaxant activity of C-type natriuretic peptide and endothelium-derived hyperpolarising factor. CARDIOVASC RES Vol.74, (3) 0008-6363 515-525.
10.1016/j.cardiores.2007.02.032
Paolocci N, Jackson MI, Lopez BE et al. (2007). The pharmacology of nitroxyl (HNO) and its therapeutic potential: Not just the janus face of NO. PHARMACOLOGY & THERAPEUTICS Vol.113, (2) 0163-7258 442-458.
10.1016/j.pharmthera.2006.11.002
Madhani M, Patra AK, Miller TW et al. (2006). Biological activity of designed photolabile metal nitrosyls: light-dependent activation of soluble guanylate cyclase and vasorelaxant properties in rat aorta.. J Med Chem Vol.49, (25) 0022-2623 7325-7330.
10.1021/jm0604629
Madhani M, Okorie M, Hobbs AJ et al. (2006). Reciprocal regulation of human soluble and particulate guanylate cyclases in vivo.. Br J Pharmacol Vol.149, (6) 0007-1188 797-801.
10.1038/sj.bjp.0706920
Villar IC, Ahluwalia A, Hobbs AJ (2006). Distinct pathways regulate endothelium derived hyperpolarising factor-mediated responses in rat mesenteric arteries. ACTA PHARMACOL SIN Vol.27, (9) 1671-4083 1276-1276.
Villar IC, Francis S, Webb A et al. (2006). Novel aspects of endothelium-dependent regulation of vascular tone. KIDNEY INT Vol.70, (5) 0085-2538 840-853.
10.1038/sj.ki.5001680
Panayiotou CM, Hobbs AJ (2006). C-Type natriuretic peptide mediates ERK1/2 phosphorylation via Gi-coupled natriuretic peptide receptor-C in rat aortic smooth muscle cells. ACTA PHARMACOL SIN Vol.27, () 1671-4083 170-170.
Marro M, Panayiotou C, Hobbs A (2006). Vascular inflammation modulates alpha 1 and beta 1 soluble guanylate cyclase promoter activity in human aortic smooth muscle cells (HASMCs). ACTA PHARMACOL SIN Vol.27, () 1671-4083 172-172.
Miller TW, Franco NE, Hobbs AJ et al. (2006). Effect of changing redox status on the activation of soluble guanylate cyclase by nitrogen oxides. NITRIC OXIDE-BIOLOGY AND CHEMISTRY Vol.14, (4) 1089-8603 A38-A38.
10.1016/j.niox.2006.04.129
Scotland RS, Duchene J, Hobbs A et al. (2006). Gender-differences in leukocyte activation in vivo: role of endothelium-derived mediators. FASEB JOURNAL Vol.20, (5) 0892-6638 A1193-A1193.
Scotland RS, Cohen M, Foster P et al. (2005). C-type natriuretic peptide inhibits leukocyte recruitment and platelet-leukocyte interactions via suppression of P-selectin expression. P NATL ACAD SCI USA Vol.102, (40) 0027-8424 14452-14457.
10.1073/pnas.0504961102
Connelly L, Madhani M, Hobbs AJ (2005). Resistance to endotoxic shock in endothelial nitric-oxide synthase (eNOS) knock-out mice: a pro-inflammatory role for eNOS-derived no in vivo.. J Biol Chem Vol.280, (11) 0021-9258 10040-10046.
10.1074/jbc.M411991200
Ahluwalia A, Villar I, Scotland RS et al. (2005). The natriuretic peptide receptor-C antagonist, M372049, blocks C-type natriuretic peptide and endothelium-derived hyperpolarizing factor-induced relaxation of resistance arteries. FASEB JOURNAL Vol.19, (5) 0892-6638 A1556-A1556.
Ahluwalia A, Hobbs AJ (2005). Endothelium-derived C-type natriuretic peptide: more than just a hyperpolarizing factor. TRENDS PHARMACOL SCI Vol.26, (3) 0165-6147 162-167.
10.1016/j.tips.2005.01.005
Scotland RS, Madhani M, Chauhan S et al. (2005). Investigation of vascular responses in endothelial nitric oxide synthase/cyclooxygenase-1 double-knockout mice - Key role for endothelium-derived hyperpolarizing factor in the regulation of blood pressure in vivo. CIRCULATION Vol.111, (6) 0009-7322 796-803.
10.1161/01.CIR.0000155238.70797.4E
Scotland RS, Ahluwalia A, Hobbs AJ (2005). C-type natniuretic peptide in vascular physiology and disease. PHARMACOL THERAPEUT Vol.105, (2) 0163-7258 85-93.
10.1016/j.pharmthera.2004.08.011
Scotland R, Foster P, Ahluwalia A et al. (2004). C-type natriuretic peptide inhibits leukocyte recruitment in vivo via natriuretic peptide receptor-C activation. CIRCULATION Vol.110, (17) 0009-7322 240-240.
Ahluwalia A, Foster P, Prescott C et al. (2004). Endothelial C-type natriuretic peptide regulates coronary blood flow and prevents ischemia-reperfusion injury. CIRCULATION Vol.110, (17) 0009-7322 77-77.
Chauhan SD, Hobbs AJ, Ahluwalia A (2004). C-type natriuretic peptide: new candidate for endothelium-derived hyperpolarising factor.. Int J Biochem Cell Biol Vol.36, (10) 1357-2725 1878-1881.
10.1016/j.biocel.2003.09.009
Hobbs A, Foster P, Prescott C et al. (2004). Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury - Novel cardioprotective role for endothelium-derived C-type natriuretic peptide. CIRCULATION Vol.110, (10) 0009-7322 1231-1235.
10.1161/01.CIR.0000141802.29945.34
Connelly L, Hobbs AJ (2004). Endothelial nitric oxide synthase promotes inducible NOS expression in LPS-challenged mice in vivo. NITRIC OXIDE-BIOLOGY AND CHEMISTRY Vol.11, (1) 1089-8603 122-122.
Madhani M, MacAllister RJ, Hobbs AJ (2004). Reciprocal interaction between soluble and particulate guanylate cyclases in vivo. NITRIC OXIDE-BIOLOGY AND CHEMISTRY Vol.11, (1) 1089-8603 120-120.
Ahluwalia A, MacAllister RJ, Hobbs AJ (2004). Vascular actions of natriuretic peptides. Cyclic GMP-dependent and -independent mechanisms.. Basic Res Cardiol Vol.99, (2) 0300-8428 83-89.
10.1007/s00395-004-0459-6
Ahluwalia A, Foster P, Scotland RS et al. (2004). Antiinflammatory activity of soluble guanylate cyclase: cGMP-dependent down-regulation of P-selectin expression and leukocyte recruitment. P NATL ACAD SCI USA Vol.101, (5) 0027-8424 1386-1391.
10.1073/pnas.0304264101
AHLUWALIA A, Hobbs A, Prescott C et al. (2004). Natriuretic peptide receptor-C regulates coronary blood flow and prevents myocardial ischemia/reperfusion injury: novel cardioprotective role for endothelium-derived C-type natriuretic peptide.. Circulation Vol.110, (10) 1231-1235.
10.1161/01.CIR.0000141802.29945.34
Hobbs AJ, Moncada S (2003). Antiplatelet properties of a novel, non-NO-based soluble guanylate cyclase activator, BAY 41-2272.. Vascul Pharmacol Vol.40, (3) 1537-1891 149-154.
10.1016/S1537-1891(03)00046-6
Madhani M, Scotland RS, MacAllister RJ et al. (2003). Vascular natriuretic peptide receptor-linked particulate guanylate cyclases are modulated by nitric oxide-cyclic GMP signalling.. Br J Pharmacol Vol.139, (7) 0007-1188 1289-1296.
10.1038/sj.bjp.0705365
Connelly L, Jacobs AT, Palacios-Callender M et al. (2003). Macrophage endothelial nitric-oxide synthase autoregulates cellular activation and pro-inflammatory protein expression.. J Biol Chem Vol.278, (29) 0021-9258 26480-26487.
10.1074/jbc.M302238200
Madhani M, MacAllister R, Hobbs A (2003). Vascular natriuretic peptide receptors modulated by NO-cyclic GMP signalling. BRITISH JOURNAL OF PHARMACOLOGY Vol.138, () 0007-1188 U17-U17.
Foster P, Mathur A, McLean P et al. (2003). Anti-leukocyte properties of a novel non NO-based soluble guanylate cyclase activator, BAY 41-2272. FASEB JOURNAL Vol.17, (5) 0892-6638 A1052-A1052.
Scotland RS, Chauhan SD, Hobbs AJ et al. (2003). Characterisation of eNOS/COX-1 double knockout mice: a novel model for the study of endothelium-derived hyperpolarising factor. FASEB JOURNAL Vol.17, (4) 0892-6638 A225-A225.
Hobbs AJ, Chauhan SD, Nilsson H et al. (2003). Endothelium-derived hyperpolarising factor (EDHF) is C-type natriuretic peptide (CNP) in mesenteric resistance arteries. FASEB JOURNAL Vol.17, (4) 0892-6638 A226-A226.
Chauhan SD, Nilsson H, Ahluwalia A et al. (2003). Release of C-type natriuretic peptide accounts for the biological activity of endothelium-derived hyperpolarizing factor. P NATL ACAD SCI USA Vol.100, (3) 0027-8424 1426-1431.
10.1073/pnas.0336365100
Kalsi JS, Rees RW, Hobbs AJ et al. (2003). BAY41-2272, a novel nitric oxide independent soluble guanylate cyclase activator, relaxes human and rabbit corpus cavernosum in vitro.. J Urol Vol.169, (2) 0022-5347 761-766.
10.1097/01.ju.0000043880.58140.69
AHLUWALIA A, Hobbs AJ, Seggara G et al. (2003). Protection against liposaccharide-induced endothelial dysfunction in resistance and conduit vasculature of iNOS knockout mice.. Faseb J Vol.17, (6) 0892-6638 773-775.
10.1096/fj.02-0668fje
Hobbs AJ, Gladwin MT, Patel RP et al. (2002). Haemoglobin: NO transporter, NO inactivator or NOne of the above?. Trends Pharmacol Sci Vol.23, (9) 0165-6147 406-411.
Hobbs AJ, Gladwin MT, Patel RP et al. (2002). Haernoglobin: NO transporter, NO inactivator or NOne of the above?. TRENDS PHARMACOL SCI Vol.23, (9) 0165-6147 406-411.
10.1016/S0165-6147(02)02067-9
Hobbs AJ (2002). Soluble guanylate cyclase: an old therapeutic target re-visited.. Br J Pharmacol Vol.136, (5) 0007-1188 637-640.
10.1038/sj.bjp.0704779
Chauhan SD, MacAllister RJ, Hobbs AJ et al. (2002). Mechanisms underlying the vasorelaxant activity of C-type natriuretic peptide (CNP) in rat mesenteric resistance arteries. FASEB J Vol.16, (4) 0892-6638 A572-A572.
Connelly L, Palacios-Callender M, Ameixa C et al. (2001). Biphasic regulation of NF-kappa B activity underlies the pro- and anti-inflammatory actions of nitric oxide.. J Immunol Vol.166, (6) 0022-1767 3873-3881.
Hussain MB, MacAllister RJ, Hobbs AJ (2001). Reciprocal regulation of cGMP-mediated vasorelaxation by soluble and particulate guanylate cyclases.. Am J Physiol Heart Circ Physiol Vol.280, (3) 0363-6135 H1151-H1159.
Selwood DL, Brummell DG, Budworth J et al. (2001). Synthesis and biological evaluation of novel pyrazoles and indazoles as activators of the nitric oxide receptor, soluble guanylate cyclase. J MED CHEM Vol.44, (1) 0022-2623 78-93.
10.1021/jm001034k
Shah S, Hobbs A, Singh R et al. (2000). Gastrointestinal motility during pregnancy: role of nitrergic component of NANC nerves. AMERICAN JOURNAL OF PHYSIOLOGY-REGULATORY INTEGRATIVE AND COMPARATIVE PHYSIOLOGY Vol.279, (4) 0363-6119 R1478-R1485.
Cavero M, Hobbs A, Madge D et al. (2000). Synthesis and biological evaluation of enantiopure thionitrites: the solid-phase synthesis and nitrosation of D-glutathione as a molecular probe.. Bioorg Med Chem Lett Vol.10, (7) 0960-894X 641-644.
10.1016/S0960-894X(00)00060-3
Hussain MB, MacAllister RJ, Hobbs AJ (2000). Regulation of cGMP-mediated vasorelaxation in mouse thoracic aorta: Interactions of the soluble and particulate guanylate cyclases. BRIT J PHARMACOL Vol.129, () 0007-1188 -.
Hussain MB, Hobbs AJ, MacAllister RJ (1999). Autoregulation of nitric oxide-soluble guanylate cyclase-cyclic GMP signalling in mouse thoracic aorta.. Br J Pharmacol Vol.128, (5) 0007-1188 1082-1088.
10.1038/sj.bjp.0702874
Wolzt M, MacAllister RJ, Davis D et al. (1999). Biochemical characterization of S-nitrosohemoglobin. Mechanisms underlying synthesis, no release, and biological activity.. J Biol Chem Vol.274, (41) 0021-9258 28983-28990.
10.1074/jbc.274.41.28983
Hussain MB, Hobbs AJ, MacAllister RJ (1999). Enhanced sensitivity of the soluble guanylate cyclase/cyclic GMP system in the eNOS knockout mouse. BRIT J PHARMACOL Vol.126, () 0007-1188 U41-U41.
Hobbs AJ, Higgs A, Moncada S (1999). Inhibition of nitric oxide synthase as a potential therapeutic target.. Annu Rev Pharmacol Toxicol Vol.39, () 0362-1642 191-220.
10.1146/annurev.pharmtox.39.1.191
Hobbs AJ (1997). Soluble guanylate cyclase: the forgotten sibling.. Trends Pharmacol Sci Vol.18, (12) 0165-6147 484-491.
Cohen GA, Hobbs AJ, Fitch RM et al. (1996). Nitric oxide regulates endothelium-dependent vasodilator responses in rabbit hindquarters vascular bed in vivo.. Am J Physiol Vol.271, (1 Pt 2) 0002-9513 H133-H139.
Hobbs AJ, Ignarro LJ (1996). Nitric oxide cyclic GMP signal transduction system. NITRIC OXIDE, PT B Vol.269, () 0076-6879 134-148.
SHAKER R, CUEVAS J, HOBBS A et al. (1995). CHANGES IN GASTROINTESTINAL SMOOTH-MUSCLE REACTIVITY DURING PREGNANCY MAY BE INDUCED BY NITRIC-OXIDE. GASTROENTEROLOGY Vol.108, (4) 0016-5085 A688-A688.
SHAH SN, CUEVAS JM, HOBBS AJ et al. (1995). ENHANCED ACTIONS OF NITRIC-OXIDE IN MODULATING GASTROINTESTINAL SMOOTH-MUSCLE FUNCTION DURING PREGNANCY. GASTROENTEROLOGY Vol.108, (4) 0016-5085 A1246-A1246.
HOBBS A, COHEN G, FITCH R et al. (1995). DIFFERENTIAL INHIBITORY EFFECT OF L-NAME ON ENDOTHELIUM-DEPENDENT RELAXATION IN-VITRO AND IN-VIVO. FASEB JOURNAL Vol.9, (3) 0892-6638 A328-A328.
COHEN G, HOBBS A, FITCH R et al. (1995). STIMULATED RELEASE OF NITRIC-OXIDE (NO) IS LINKED TO ALPHA-ADRENOCEPTOR ACTIVATION IN-VIVO. FASEB JOURNAL Vol.9, (3) 0892-6638 A328-A328.
SHAH S, CUEVAS J, HOBBS A et al. (1995). THE ROLE OF NITRIC-OXIDE IN MODULATING GASTROINTESTINAL SMOOTH-MUSCLE REACTIVITY DURING PREGNANCY. FASEB JOURNAL Vol.9, (3) 0892-6638 A86-A86.
Griscavage JM, Hobbs AJ, Ignarro LJ (1995). Negative modulation of nitric oxide synthase by nitric oxide and nitroso compounds.. Adv Pharmacol Vol.34, () 1054-3589 215-234.
HOBBS A, FUKUTO J, IGNARRO L (1994). FORMATION OF FREE NITRIC-OXIDE FROM L-ARGININE BY NITRIC-OXIDE SYNTHASE - DIRECT ENHANCEMENT OF GENERATION BY SUPEROXIDE-DISMUTASE. PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA Vol.91, (23) 0027-8424 10992-10996.
10.1073/pnas.91.23.10992
HOBBS A, GRISCAVAGE J, ROGERS N et al. (1994). FORMATION OF FREE NITRIC-OXIDE FROM L-ARGININE BY NITRIC-OXIDE SYNTHASE AND ENHANCEMENT OF GENERATION BY SUPEROXIDE-DISMUTASE. FASEB JOURNAL Vol.8, (4) 0892-6638 A360-A360.
HOBBS A, GRISCAVAGE J, ROGERS N et al. (1994). FORMATION OF FREE NITRIC OXIDE FROM L-ARGININE BY NITRIC OXIDE SYNTHASE AND ENHANCEMENT OF GENERATION BY SUPEROXIDE DISMUTASE. BIOLOGY OF NITRIC OXIDE, PT 4 Vol.8, () 0966-4068 36-42.
Fukuto JM, Hobbs AJ, Ignarro LJ (1993). Conversion of nitroxyl (HNO) to nitric oxide (NO) in biological systems: the role of physiological oxidants and relevance to the biological activity of HNO.. Biochem Biophys Res Commun Vol.196, (2) 0006-291X 707-713.
10.1006/bbrc.1993.2307
Brave SR, Bhat S, Hobbs AJ et al. (1993). The influence of L-NG-nitro-arginine on sympathetic nerve induced contraction and noradrenaline release in the rat isolated anococcygeus muscle.. J Auton Pharmacol Vol.13, (3) 0144-1795 219-225.
Gibson A, Babbedge R, Brave SR et al. (1992). An investigation of some S-nitrosothiols, and of hydroxy-arginine, on the mouse anococcygeus.. Br J Pharmacol Vol.107, (3) 0007-1188 715-721.
Hobbs AJ, Tucker JF, Gibson A (1991). Differentiation by hydroquinone of relaxations induced by exogenous and endogenous nitrates in non-vascular smooth muscle: role of superoxide anions.. Br J Pharmacol Vol.104, (3) 0007-1188 645-650.
Brave SR, Hobbs AJ, Gibson A et al. (1991). The influence of L-NG-nitro-arginine on field stimulation induced contractions and acetylcholine release in guinea pig isolated tracheal smooth muscle.. Biochem Biophys Res Commun Vol.179, (2) 0006-291X 1017-1022.
Mirzazadeh S, Hobbs AJ, Tucker JF et al. (1991). Cyclic nucleotide content of the rat anococcygeus during relaxations induced by drugs or by non-adrenergic, non-cholinergic field stimulation.. J Pharm Pharmacol Vol.43, (4) 0022-3573 247-251.
Tucker JF, Brave SR, Charalambous L et al. (1990). L-NG-nitro arginine inhibits non-adrenergic, non-cholinergic relaxations of guinea-pig isolated tracheal smooth muscle.. Br J Pharmacol Vol.100, (4) 0007-1188 663-664.
Hobbs AJ, Gibson A (1990). L-NG-nitro-arginine and its methyl ester are potent inhibitors of non-adrenergic, non-cholinergic transmission in the rat anococcygeus.. Br J Pharmacol Vol.100, (4) 0007-1188 749-752.
Gibson A, Mirzazadeh S, Hobbs AJ et al. (1990). L-NG-monomethyl arginine and L-NG-nitro arginine inhibit non-adrenergic, non-cholinergic relaxation of the mouse anococcygeus muscle.. Br J Pharmacol Vol.99, (3) 0007-1188 602-606.

Sponsors

British Lung Foundation
British Heart FoundationNational Heart Lung and Blood InstituteWellcome Trust

Collaborators

Internal: Prof. A. Ahluwalia (QMUL); Dr. T. Chowdhury (QMUL);
External: Prof. R. MacAllister (UCL); Prof. R. Chambers(UCL); Dr. C. Scotten (UCL); Prof. M. Wilkins (Imperial); Dr. Lan Zhao (Imperial); Prof. L. Ignarro Nobel Laureate (UCLA); Prof. J. Fukuto (Sonoma State); Prof. J. Klinger (Providence); Prof. H. Schmidt (University of Maastricht); Prof. P. Mascharak (UC Santa Cruz); Dr. B. Kemp-Harper (Monash University); Dr. J.-P. Stasch (Bayer AG); Prof. F.-O. Levy (University of Oslo).

Contact

Adrian J Hobbs, PhD
Professor of Cardiovascular Pharmacology
William Harvey Heart Centre (1st Floor)
Barts & The London School of Medicine & Dentistry
Queen Mary University of London
Charterhouse Square
London, EC1M 6BQ
T: +44 (0)207 882 5778
F: +44 (0)207 882 8403
E: This email address is being protected from spambots. You need JavaScript enabled to view it.

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