PROLONGED EFFECTS OF SHORT-TERM FOSINOPRIL ON BLOOD-PRESSURE AND VASCULAR MORPHOLOGY AND FUNCTION IN RATS

The aim of this study was to evaluate the delayed effects of an angiot ensin converting enzyme (ACE) inhibitor on blood pressure and on struc tural and functional alterations in mesenteric small resistance arteri es of spontaneously hypertensive rats (SHR). The ACE inhibitor fosinop ril (25 mg/kg/day) was administered according to three different sched ules: in one group of SHR from 4 to 8 weeks of age (n = 12), in a seco nd group from 8 to 12 weeks of age (n = 15), and in a third group from 4 to 12 weeks of age (n = 12). Eighteen untreated SHR and 18 untreate d Wistar-Kyoto rats served as controls. About half the animals in each group were killed at 13 weeks of age, and the remaining were killed a t 38 weeks of age. After death, relative left ventricular mass (left v entricular weight/body weight) was calculated. Vascular morphology (me dia:lumen ratio) and function (responses to norepinephrine and acetylc holine) in mesenteric small resistance arteries were then assessed usi ng a micromyographic technique. Short-term fosinopril, given either be fore or after the development of hypertension, persistently reduced (b ut did not normalize) systolic blood pressure, vascular structural alt erations, and reactivity to norepinephrine in mesenteric resistance ar teries in SHE. These favorable effects were maintained at least for 26 to 30 weeks after treatment withdrawal. The endothelium-dependent vas odilator response to acetylcholine was improved at 13 but not at 38 we eks of age, in treated SHR. Therefore, the vascular response to norepi nephrine seems to be dependent mainly on the structure of the vessels, whereas endothelial function is probably more linked to the hemodynam ic load. (C) 1997 American Journal of Hypertension, Ltd.