Ace-inhibition with quinapril modulates the nitric oxide pathway in normotensive rats.

Angiotensin-converting enzyme (ACE) inhibitors exert some cardiovascular benefits by improving endothelial function. We evaluated the effects of chronic treatment with quinapril (Q) on the l -arginine/nitric oxide (NO) pathway in normotensive rats under baseline and inflammatory conditions. The role of bradykinin was also investigated. The animals received for 1 week either the ACE-inhibitor Q (1 and 10 mg/kg/day), the B(2)receptor antagonist HOE 140, Q+HOE 140, or no drug. At the end of chronic treatment, rats underwent either a 6-h placebo or an E. coli endotoxin challenge. The following measurements were made: (i) endothelial and inducible NO synthase (eNOS and iNOS) protein expression; (ii) eNOS/iNOS activity; (iii) serum levels of nitrite/nitrate and tumour necrosis factor (TNF)- alpha; (iv) NO in the expired air (eNO). Q increased baseline aortic eNOS protein expression (up to 99%, P<0.001) and activity (l -citrulline synthesis up to 94%, P<0.01; serum nitrite/nitrate up to 55%, P<0.05). HOE 140 partially reversed Q-induced upregulation of eNOS (P<0.05). Moreover, Q counteracted LPS effects, i.e. increased the impaired eNOS pathway and limited iNOS induction (up to 94 and 24%, respectively), and reduced the increased nitrite/nitrate and TNF- alpha serum levels as well as eNO (up to 25, 38 and 28%, respectively, P<0.01 for all comparisons). HOE 140 did not influence Q effects on iNOS during endotoxaemia. In conclusion, in (patho)physiological conditions in rats, Q up-regulated eNOS with a bradykinin-mediated mechanism, while downregulated iNOS with a possible TNF- alpha -mediated mechanism. Copyright 2001 Academic Press.