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

Angiotensin-converting enzyme (ACE) inhibitors exert some cardiovascular be nefits by improving endothelial function. We evaluated the effects of chron ic treatment with quinapril (Q) on the (L)-arginine/nitric oxide (NO) pathw ay in normotensive rats under baseline and inflammatory conditions. The rol e of bradykinin was also investigated. The animals received for 1 week eith er the ACE-inhibitor Q (1 and 10 mg/kg/day). the B-2, receptor antagonist H OE 140, Q + HOE 140, or no drug. At the end of chronic treatment, rats unde rwent either a 6-h placebo or an E. coli endotoxin challenge. The following measurements were made: (i) endothelial and inducible NO synthase (eNOS an d iNOS) protein expression: (ii) eNOS/iNOS activity; (iii) serum levels of nitrite/ nitrate and tumour necrosis factor (TNF)-alpha; (iv) NO in the exp ired 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; ser um nitrite/ nitrate up to 55%, P<0.05). HOE 140 partially reversed Q-induce d 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 a nd 24%, respectively), and reduced the increased nitrite/nitrate and TNF-al pha 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 e ndotoxaemia. In conclusion, in (patho)physiological conditions in rats, Q u p-regulated eNOS with a bradykinin-mediated mechanism. while downregulated iNOS with a possible TNF-<alpha>-mediated mechanism. (C) 2001 Academic Pres s.