ANGIOTENSIN-II INDUCES CARDIOVASCULAR HYPERTROPHY IN PERINDOPRIL-TREATED RATS

Objective: To investigate whether angiotensin II (Ang II) exerts a direct effect on cardiovascular hypertrophy in the spontaneously hypertensive rat or acts indirectly through elevation of blood pressure. Design: Immature (7-week-old) and mature (14-week-old) spontaneously hypertensive rats were treated for 8 and 6 weeks, respectively, with an angiotensin converting enzyme inhibitor to block the in vivo production of Ang II and concomitantly infused with either a presser dose of Ang II or noradrenaline. Methods: At the termination of treatment, vascular smooth muscle cell growth was assessed in the aorta and mesenteric arterioles. Results: In the young rats systolic blood pressure was not significantly different in the Ang II- and noradrenaline-infused groups. In the mature rats blood pressure was elevated in the Ang II-infused rats above that in the untreated and noradrenaline-infused groups, in which blood pressure was not significantly different. Ang II infusion induced cardiac hypertrophy and medial hypertrophy both in the aorta and in first-order mesenteric arterioles, accompanied by induction of smooth muscle polyploidy. The growth response to Ang II differed in the large and small vessels, with a marked induction of smooth muscle hyperplasia in the mesenteric arterioles but no change in cell number in the aorta. Infusion of noradrenaline did not induce cardiac or vascular hypertrophy, levels being similar to those in the rats treated with perindopril only. Conclusion: These results suggest that Ang II can directly stimulate cardiac and vascular hypertrophy in the spontaneously hypertensive rat, independently of its effect on blood pressure.