Vasoactive Peptides and Their Receptors

Abstract

Peptides act as vasoconstrictors (for instance angiotensins, vasopressin) or vasodilators (the kinins, the neurokinins), both through direct activation of specific receptors in the vascular smooth muscles or indirectly through the release of other endogenous inhibitors of the vascular tone. Kinins and neurokinins as well as their multiple receptors have been analyzed in the present study to assess the possible contributions of peptides to vasodilatation. Kinin receptors, B₁ and B₂, have been characterized, using new selective agonists and antagonists. B₁ and B₂ receptors appear to present in endothelium (B2) and in smooth muscles (B₂, B₁) of a variety of isolated vessels of the dog and the rabbit, where they subserve both stimulatory and inhibitory effects. Vasodilator inhibitory mechanisms depend on the release of the endothelium-relaxing factor and/or of prostanoids from the endothelium or the smooth muscles, especially in the dog renal vessels, where both B₁and B₂ receptors appear to be involved in causing vasodilatation. B₂ receptors have also been shown to activate cardiovascular reflexes through a direct action on sensory fibers or on reflexogenic areas of the epicardium. Three types of receptors for neurokinins, namely NK-1, NK-2 and NK-3, have been identified by the use of naturally occurring peptides and of some analogues that act as selective agonists of a single receptor type. NK-1 receptors (particularly sensitive to substance P) have been shown to be present in endothelia where they promote the release of the endothelium relaxing factor, while NK-2 receptors (sensitive to neurokinin A) are found in the pulmonary artery of the rabbit and act directly to contract the smooth muscle. NK-3 receptors (sensitive to neurokinin B) may be present in the veins where they act as venoconstrictors, increasing also the vascular permeability. Thus, peptides and their receptors participate through various mechanisms in the regulation of vascular tone and peripheral blood flow.