Pharmacology of Neurohypophyseal Hormones and their Synthetic Analogues in the Terminal Vascular Bed

Abstract

A study was undertaken to determine the vasoactive properties of the natural mammalian neurohypophyseal hormones - vasopressin and oxytocin - along with several of their synthetic analogues. Vascular smooth muscle actions were studied by direct microscopic visualization of the rat mesoappendix with the test peptides administered topically and intravenously followed by observation of the vascular response to standard doses of constrictor catecholamines. Comparative pharmacologic studies were also made on in-vitro vascular smooth muscle preparations. The observations indicate the following: The posterior-pituitary hormones and their analogues exhibit selective microvascular effects, having at least 2 new and distinct gradients of constrictor activity, in the microcirculation, which are different from those towards the usual physiologic stimuli (e.g. catecholamines and electrical stimuli). The constrictor reactivity gradients and affinity of a particular neurohypophyseal peptide for a particular type of microvessel may depend on the basicity and length of the side chain of the amino acid moiety in position 8. These neurohypophyseal peptides can induce either catecholamine potentiation or inhibition in vascular muscle. These hormones may also cause smooth muscle relaxation in certain regional vascular beds in some mammalian species. The posterior-pituitary hormones may play an important role in the local regulation of blood flow. Interest in such agents seems warranted in view of the therapeutic potential of drugs with selective vasomotor effects on the exchange vessels.