Cardioprotective Action of Perindopril versus Candesartan in Renovascular Hypertensive Rats
OBJECTIVE To investigate the role of angiotensin II (Ang II) in cardiovascular hypertrophy in the Goldblatt one-kidney, one clip (1-K, 1C) renal hypertensive rat. METHODS Six-week-old Wistar-Kyoto (WKY) rats underwent uninephrectomy and left renal artery clipping. After surgery, rats were treated with perindopril, an angiotensin converting enzyme (ACE) inhibitor, or losartan, an Ang II type 1 (AT1) receptor antagonist, for 4 weeks. Untreated 1-K, 1C rats and uninephrectomized (sham) rats served as controls. RESULTS The rise in systolic blood pressure in the perindopril-treated and losartan-treated rats was not significantly different from that in the untreated 1-K, 1C group throughout the treatment period. At 4 weeks after surgery the heart weight:body weight ratios of the untreated 1-K, 1C and losartan-treated 1-K, 1C groups were significantly greater than for sham-operated normotensive rats and hypertensive perindopril-treated rats. The total number of smooth muscle cells in the thoracic aortae of the 1-K, 1C untreated, losartan-treated 1-K, 1C and sham groups were similar. However, after treatment the aortae of the perindopril-treated group contained significantly fewer smooth muscle cells. The medial cross-sectional wall area and wall: lumen ratio were similar in the 1-K, 1C untreated and perindopril-treated 1-K, 1C groups. CONCLUSION These results suggest that Ang II, via its effects on cardiac and vascular AT1 receptors, does not contribute to the development of cardiovascular hypertrophy in the 1-K, 1C rat. Attenuation of cardiac and vascular growth after ACE inhibition appears to be mediated by mechanisms independent of the actions of the renin-angiotensin system.