EFFECTS OF LOW AND HIGH-DOSES OF FOSINOPRIL ON THE STRUCTURE AND FUNCTION OF RESISTANCE ARTERIES

It has been suggested that angiotensin-converting enzyme inhibitors ma y induce a significant regression of cardiovascular hypertrophy not on ly through blood pressure reduction but also as a possible consequence of growth factor inhibition. The aim of this study was to evaluate th e effects of the angiotensin-converting enzyme inhibitor fosinopril, g iven either at a hypotensive high dose or a nonhypotensive low dose, o n structural and functional alterations of mesenteric resistance arter ies and on cardiac mass in spontaneously hypertensive rats (SHR) and c ontrol Wistar-Kyoto rats. Fosinopril was administered in the drinking water from 6 to 12 weeks of age. Rats were killed at 12 weeks, and the ratio of heart weight to body weight was measured. Mesenteric arterio les were dissected and mounted on a micromyograph (Mulvany's technique ). Vascular morphology (media-lumen ratio, media thickness) and endoth elial function (response to acetylcholine) were then assessed. During the 6 weeks of treatment, systolic pressure in SHR treated with high-d ose fosinopril was significantly lower compared with that in untreated SHR, whereas no difference was observed with low-dose fosinopril. In SHR treated with both high-dose and low-dose fosinopril, a statistical ly significant reduction of vascular structural alterations, in terms of both media-lumen ratio and media thickness, was observed. The ratio of heart weight to body weight was reduced only in SHR treated with h igh-dose fosinopril. An improvement in the endothelium-dependent relax ation to acetylcholine was observed in SHR treated with high-dose fosi nopril compared with untreated SHR, whereas in SHR treated with low-do se fosinopril no improvement in endothelial function was detected. In conclusion, low-dose fosinopril selectively prevented the structural b ut not functional vascular alterations in SHR, thus suggesting a possi ble interference of angiotensin-converting enzyme inhibitors with grow th factors, at least in the peripheral vasculature.