The Pharmacology of Vasodilator Agents on Vascular Muscle

Abstract

The aims of this study were: i) to evaluate rat vascular muscle preparations as model systems for predicting or assessing vasodilator efficacy on human vasculature; ii) to use rat vascular muscle to classify vasodilators by their spectrum of activity and to investigate the mechanisms of action underlying this empirical division. Rat portal vein and aortic preparations were used and the effects of vasodilator agents upon the isometric tension developed in response to various stimuli were assessed. Four parameters of portal vein reactivity were measured: spontaneous activity and contractions induced by KCl, noradrenaline or electrical field stimulation. It was found that not all vasodilators inhibited the parameters of reactivity in the portal vein to a similar degree; some agents (NP, GTN, and TOLM) caused a selective suppression of spontaneous activity, it was upon this basis that the vasodilators were classified. Similar experiments were carried out for selected vasodilators on responses of the rat aorta. When the results obtained from these experiments were compared with published data from human vessels it was concluded that: i) the action of vasodilators on the spontaneous activity of the portal vein most closely resembled the actions of these agents on human hand veins; ii) the rat aorta was a poor model of the action of vasodilators on human arterioles. The mechanistic basis of selectivity of inhibition of portal vein spontaneous activity by NP was investigated. Kreye (1981) has suggested NP acted by causing vascular muscle hyperpolarization and consequently the action of hyperpolarizing treatments on the portal vein was investigated. Hyperpolarizing events caused a selective suppression of portal vein spontaneous activity similar to that seen with NP, consequently it may be that selective suppression of spontaneous activity of the portal vein is indicative of membrane hyperpolarization. Possible mechanisms by which NP, and other agents, caused hyperpolarization by alteration of Cl⁻ and K⁺ handling were also investigated.