Peptides and the circulation

Summary

In health coronary blood flow is automatically regulated at the level of small vessels to adjust flow to changes in perfusion pressure and myocardial oxygen demand. Coronary disease is associated with the occurrence of flow limiting resistance in the epicardial (large) arteries which is partly fixed and dynamic depending on the relative contributions of atherona, thrombosis and constriction and which causes the myocardial ischaemia seen in the various clinical presentations. There are many mediators of normal control mechanisms and pathological coronary responses; some are recently discovered such as the vasoactive peptides and some have been known for many years but their relevance has been clarified by recent research.

Neuropeptide Y is a sympathetic neurotransmitter which constricts small coronary vessels and, in the experimental situation, causes a flow reduction sufficient to induce myocardial ischaemia without any effect on the larger coronary arteries. Its effect is mainly direct through post junctional NPY receptors, Endothelin is the most potent vasoconstrictor peptide yet discovered, released from endothelial cells with a very long duration of action; its role remains to be elucidated. Vasopressin, a circulating vasoconstrictor peptide released from the pituitary gland, is important in the maintenance of blood pressure following acute haemorrhage and is used to reduce bleeding from eosophageal varices. Occasional reports of vasopressin induced myocardial ischaemia exist. The circulating renin angiotensin system provides a rapid homeostatic response to acute changes in blood pressure and fluid and electrolyte status and may operate on a local tissue level. The kallikrein kinin system is activated in septicaemic and endotoxic shock producing marked vasodilatation and hypotension which can be attenuated by a bradykinin antagonist. Somatostation is widespread in the body; it inhibits the release of growth hormone and insulin and selectively reduces portal venous pressure during intravenous infusion, possibly by inhibition of gut vasodilator peptides. Calcitonin gene related peptide and substance P are both dilator neurotransmitter peptides found in human heart, the former long acting and the latter short acting. Atrial natriuretic factor is a peptide produced locally in the atria of human hearts and regulates blood volume by responding to atrial distension.

It is clear that the control of the circulation is complex and involves peptide hormones and neurotransmitters. This realisation has served to stimulate much research in cardiovascular control mechanisms.