Does antihypertensive therapy improve the function of the vascular endothelium?

Abstract

C hronic treatment of genetically hypertensive rats with the angiotensin converting enzyme inhibitor cilazapril reduces the hypertrophic changes of the vasculature that accompany the progression of the disease. 1 Other antihypertensive agents such as the peripheral vasodilator hydralazine are less effective. In the accompanying article, Clozel et al 2 extend the investigation of the antihypertensive effects of angiotensin converting enzyme inhibitors to the function of the vascular endothelium in spontaneously hypertensive rats. In these experiments, spontaneously hypertensive rats were treated with either cilazapril or hydralazine for 4 weeks. Other groups of rats were treated with cilazapril or another angiotensin converting enzyme inhibitor, captopril, for 4 days. In all groups, the antihypertensive therapies significantly reduced mean arterial blood pressure. After the treatment periods, the function of the endothelium and smooth muscle was examined in rings cut from the aorta and suspended in organ chambers for the measurement of isometric force. Relaxations to acetylcholine, which depend on the integrity of the endothelial cells, were reduced in genetically hypertensive rats as has been described by others. 34 Only in hypertensive animals treated with the converting enzyme inhibitors was there significant enhancement of these endothelium-dependent relaxations to acetylcholine. This enhancement is most likely due to a direct effect on the endothelium rather than to changes in the sensitivity of the vascular smooth muscle to endothelium-derived relaxing factors because relaxations to a nitrovasodilator, which may act similarly to an endotheliumderived relaxing factor, 3 were not affected by the antihypertensive treatments.In addition to depressed endothelium-dependent relaxations, increased sensitivity to the vasoconstrictor agent serotonin has been implicated in the maintenance of hypertension.6 Indeed, in spontaneously hypertensive rats, contractions caused by this amine are greater when the endothelial cells are present. This observation suggests that the endothelial cells release a contractile factor in response to serotonergic stimulation. Again, only in rats treated with converting enzyme inhibitors were these contractions to serotonin reduced.The results of the study of Clozel et al 2 suggest that although antihypertensive therapies reduce mean arterial pressure, the consequences of selective therapies are very different. The converting enzyme inhibitors affect morphological changes as well as functional changes of the vasculature. These changes probably result from effects distinct from the decreased pressure stimulus to the blood vessel wall as decreases in mean arterial pressure were similar between groups of rats given converting enzyme inhibitors and hydralazine. Further, improvement of endothelium-dependent relaxations were observed after only 4 days of treatment with the converting enzyme inhibitors, whereas changes were not observed with comparable decreases in mean arterial pressure with 4 w...

Ramiprilat enhances endothelial autacoid formation by inhibiting breakdown of endothelium-derived bradykinin.

“…22 The mechanism by which ACE inhibitors enhance agonist-induced endothelium-dependent relaxation in normotensive, 23 hypertensive, 21 and hypercholesterolemic animals 22 is unknown, but seems to be distinct from the blood pressure-lowering action of ACE inhibitors. 21 - 24 It has been speculated that ACE inhibitors promote vasodilation by increasing the level of bradykinin generated in subthreshold concentration in the vascular wall by a local kallikrein-kinin system.…”