Acute Actions of Natriuretic Peptides in Coronary Vasculature and Ischaemic Myocardium

Yohann      Rautureau; Gary   F.   Baxter

Abstract

The natriuretic peptides are a family of widely distributed polypeptide mediators that exert a range of actions in several body systems. In cardiovascular homeostasis, the endocrine roles of the cardiac-derived atrial and B-type natriuretic peptide (ANP and BNP) in regulating central fluid volume and blood pressure have been recognised for two decades. However, there is a growing realisation that natriuretic peptide actions go far beyond their endocrine effects and that local (autocrine / paracrine) regulatory actions within the heart and coronary vasculature may be of comparable importance, especially in disease states where tissue and circulating levels of the peptides rise markedly. In acute myocardial ischaemia, release of BNP occurs rapidly from ventricular myocardium, prompting speculation that the early activation of the natriuretic peptide receptor / cGMP signalling system may be an important autocrine / paracrine response in cardiac ischaemia. The autocrine / paracrine actions include inotropic effects, the acute regulation of coronary vascular tone and the attenuation of the susceptibility of myocardium to ischaemic injury. The effects of longer-term upregulation of natriuretic peptide expression in the heart could include the suppression of growth and proliferative responses in a variety of myocardial and vascular cells. In a variety of preparations, acute exposure of epicardial coronary arteries to pharmacological concentrations of natriuretic peptides evokes vasorelaxation, although in coronary microvessels, evidence for a vasorelaxant action of the peptides is less consistent. The mechanisms of the coronary vasorelaxant action are unclear but limited evidence suggests an endothelium-dependent component. In ischaemic myocardium, acute treatment with BNP prior to and during coronary artery occlusion exerts a markedly protective, concentration-dependent infarct-limiting action. This cytoprotective effect of the natriuretic peptide signalling pathway might conceivably represent an alternative endogenous salvage pathway in myocardium which is potentially exploitable therapeutically. Taken together, the acute actions of natriuretic peptides on the coronary vasculature and in myocardial ischaemia suggest a profile of activity that may be therapeutically beneficial in the management of patients with acute coronary syndromes.

Keywords: natriuretic peptide, anp, bnp, cnp, npr-a, npr-b, guanylyl cyclase, cgmp, coronary arteries, ischaemia, myocardium, infarction