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CNP, but not ANP or BNP, Relax Human Isolated Subcutaneous Resistance Arteries by an Action Involving Cyclic GMP and BKCa Channels

Clinical Pharmacology, National Heart & Lung Institute, Faculty of Medicine, Imperial College London, W2 1NY, UK

Alun D Hughes

Clinical Pharmacology, National Heart & Lung Institute, Faculty of Medicine, Imperial College London, W2 1NY, UK, a.hughes{at}imperial.ac.uk

Natriuretic peptides play an important role in sodium regulation and blood pressure (BP) control. We examined the effects of atrial natriuetic peptide (ANP), brain natriuretic peptide (BNP) and C-type natriuretic peptide (CNP) on human isolated resistance arteries and the mechanisms involved in vasorelaxation. Human subcutaneous resistance arteries were mounted in an isometric myograph and contracted with phenylephrine. CNP, but not ANP or BNP, relaxed arteries in a concentration dependent manner. The action of CNP was unaffected by removal of the endothelium, inhibition of nitric oxide synthase by NG-monomethyl-Larginine or inhibition of soluble guanylate cyclase by 1H-[1,2,4] oxadiazolo [4,3-alpha] quinoxalin-1-one. Blockade of cyclic GMP-dependent kinase by 8- bromoguanosine-3', 5'- cyclic monophosphorothioate, Rp-isomer (Rp-8-Br-cGMPS) inhibited CNP relaxation. CNP relaxation was also inhibited by high potassium or iberiotoxin, indicating that it was due to opening of BK_Ca channels. Omapatrilat, a vasopeptidase inhibitor of neutral endopeptidase and angiotensin-converting enzyme, enhanced the effect of CNP and inhibited responses to Ang I. In summary, CNP, but not ANP or BNP, relaxes human resistance arteries by activating cyclic GMP-dependent kinase and BK_Ca. The effects of CNP are enhanced by vasopeptidase inhibition and this may contribute to the vasodilator effects of these agents in vivo. Since CNP is widely present in endothelium it may play a role in the regulation of peripheral resistance in man in physiological and pathological circumstances.

Key Words: Natriuretic peptides • ANP • BNP • CNP • Omapatrilat • Neutral endopeptidase • Ca2+-activated potassium channels • Cyclic GMP

Journal of Renin-Angiotensin-Aldosterone System, Vol. 7, No. 2, 87-91 (2006)
DOI: 10.3317/jraas.2006.014


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