Enalapril prevents aortic hyperreactivity and remodelling in one-kidney, one-clip hypertensive rats without reducing arterial pressure.
1. The present study was designed to evaluate the blood pressure-independent effects of angiotensin-converting enzyme (ACE) inhibition on cardiovascular structure and function in one-kidney, one-clip (1K1C) hypertensive rats. 2. The study was conducted in four groups of rats: (i) uninephrectomized normotensive rats (1K); (ii) 1K1C hypertensive rats; (iii) 1K rats treated with enalapril; and (iv) 1K1C rats treated with enalapril. Enalapril treatment (20 mg/kg per day, p.o.) was started after surgery to induce hypertension or nephrectomy and continued for 5 weeks. 3. The increase in blood pressure of 1K1C rats was associated with activation of cardiac and aortic, but not plasma, ACE activity and with hypertrophy of both heart and aorta. No difference in cardiac output and in vitro systolic function was observed among the groups. Hypertrophied aorta isolated from 1K1C rats displayed increased sensitivity to phenylephrine (PE) and unaltered responses to both acetylcholine (ACh) and sodium nitroprusside compared with the 1K group. 4. Enalapril treatment effectively inhibited plasma and tissue ACE activity in 1K1C and 1K rats. Enalapril did not prevent the development of hypertension and cardiac hypertrophy nor did it change haemodynamic parameters in 1K1C rats. However, enalapril prevented the increase in aortic media thickness and cross-sectional area and restored the hypersensitivity to PE in aortic rings of 1K1C rats. The endothelium-dependent response to ACh was enhanced by enalapril in the aorta of 1K but not 1K1C rats. 5. These results suggest a role for activated local angiotensin II generation in aortic but not cardiac hypertrophy secondary to 1K1C hypertension.
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Departamento de Farmacologia, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, Brasil.
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D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects / Q000503:physiopathology; D001794:Blood Pressure / Q000187:drug effects*; D004656:Enalapril / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000503:physiopathology*; D008297:Male; D009206:Myocardium / Q000473:pathology; D007703:Peptidyl-Dipeptidase A / Q000097:blood / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004656:Enalapril; D007703:Peptidyl-Dipeptidase A