Endothelium-dependent relaxation effects in aorta from hypertensive rats

Abstract

Since the original observations by Furchgott & Zawadzki(1980), it has been repeatedly demonstrated that the endothelium has an important role in the effects of many vasodilating substances (for review: Furchgott, 1983). In a previous study we showed that histamine and acetylcholine produce relaxations of pre-contracted rat aorta preparations on the condition that intact endothelial cells are present. Using a “sandwich” technique, it was demonstrated that both agonists induce the generation of (a) mediator(s) in the endothelium, which leads to relaxation of the vascular smooth muscle cells (Furchgott & Zawadzki, 1980; Van de Voorde & Leusen, 1983). Endothelial changes have been implicated in several vascular diseases of major clinical importance (Chand & Altura, 1981). One of these, hypertension, is known to induce endothelial damages (Hazama et al., 1978) and replication (Schwartz & Benditt, 1977; Daniel et al., 1982), intimal thickening (Still, 1968) and changes in arachidonate metabolism (Rioux & Regoli, 1975; Limas et al., 1981; Dickens et al., 1982; Lennon & Poyser, 1983), which is a suspected pathway for the production of the endothelium-derived relaxing factor (Furchgott, 1983; Van de Voorde & Leusen, 1983).