ANGIOTENSIN-II INDUCES CARDIOVASCULAR HYPERTROPHY IN PERINDOPRIL-TREATED RATS

Objective: To investigate whether angiotensin II (Ang II) exerts a dir ect effect on cardiovascular hypertrophy in the spontaneously hyperten sive rat or acts indirectly through elevation of blood pressure. Desig n: Immature (7-week-old) and mature (14-week-old) spontaneously hypert ensive rats were treated for 8 and 6 weeks, respectively, with an angi otensin 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 art erioles. Results: In the young rats systolic blood pressure was not si gnificantly 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 a nd in first-order mesenteric arterioles, accompanied by induction of s mooth muscle polyploidy. The growth response to Ang II differed in the large and small vessels, with a marked induction of smooth muscle hyp erplasia in the mesenteric arterioles but no change in cell number in the aorta. Infusion of noradrenaline did not induce cardiac or vascula r hypertrophy, levels being similar to those in the rats treated with perindopril only. Conclusion: These results suggest that Ang II can di rectly stimulate cardiac and vascular hypertrophy in the spontaneously hypertensive rat, independently of its effect on blood pressure.