Unchanged cardiac angiotensin II levels accompany losartan-sensitive cardiac injury due to nitric oxide synthase inhibition

Chronic nitric oxide synthase (NOS) inhibition results in hypertension and myocardial injury. In a rapid and severe model of chronic NOS inhibition, w e determined the role of angiotensin II in these effects by using angiotens in II receptor blockade and by measuring cardiac angiotensin II concentrati ons before and during development of cardiac damage. Rats received either n o treatment, the NOS inhibitor N omega-nitro-L-arginine (L-NNA; 500 mg/l), the angiotensin AT, receptor antagonist losartan (400 mg/kg chow), or L-NNA plus losartan for 21 days. In the second protocol, five groups of rats rec eived L-NNA (500 mg/l) for 0, 4, 7, 14 and 21 days, respectively. L-NNA inc reased systolic blood pressure (SBP) (227 +/- 8 versus 143 +/- 6 mm Hg; P < 0.01), heart weight index (0.44 +/- 0.02 versus 0.32 +/- 0.01; P < 0.01) a nd induced coronary vasculitis and myocardial necrosis. Go-treatment with l osartan prevented all changes. L-NNA during 4 days decreased cardiac angiot ensin II (23 +/- 4 versus 61 +/- 15 fmol/g; P < 0.05). Although after 7 day s, fresh infarcts and after 14 days organized infarcts were present, cardia c angiotensin II was only slightly increased after 21 days (100 +/- 10 fmol /g; P < 0.05). In conclusion, losartan-sensitive cardiac damage due to chro nic NOS inhibition is not associated with primary increase of cardiac angio tensin II, suggesting that chronic NOS inhibition increases cardiac sensiti vity for angiotensin II. (C) 2000 Elsevier Science B.V. All rights reserved .