title: Ace-inhibition with quinapril modulates the nitric oxide pathway in normotensive rats.
abstract: 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.
authors.affiliation: Salvatore Maugeri Foundation, IRCCS, Cardiovascular Pathophysiology Research Centre, Gussago, Italy.
authors.forename: T
authors.initials: T
authors.lastname: Bachetti
authors.forename: L
authors.initials: L
authors.lastname: Comini
authors.forename: E
authors.initials: E
authors.lastname: Pasini
authors.forename: A
authors.initials: A
authors.lastname: Cargnoni
authors.forename: S
authors.initials: S
authors.lastname: Curello
authors.forename: R
authors.initials: R
authors.lastname: Ferrari
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000201:enzymology; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000378:metabolism / Q000502:physiology; D065168:Bradykinin Receptor Antagonists; D002956:Citrulline / Q000096:biosynthesis; D007546:Isoquinolines / Q000008:administration & dosage / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000008:administration & dosage / Q000276:immunology; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000096:biosynthesis*; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000077583:Quinapril; D051381:Rats; D017207:Rats, Sprague-Dawley; D043782:Receptor, Bradykinin B2; D015398:Signal Transduction / Q000502:physiology*; D044005:Tetrahydroisoquinolines; D014409:Tumor Necrosis Factor-alpha / Q000032:analysis
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D065168:Bradykinin Receptor Antagonists; D007546:Isoquinolines; D008070:Lipopolysaccharides; D043782:Receptor, Bradykinin B2; D044005:Tetrahydroisoquinolines; D014409:Tumor Necrosis Factor-alpha; D002956:Citrulline; D009569:Nitric Oxide; C065679:icatibant; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III; C496318:Nos2 protein, rat; C496316:Nos3 protein, rat; D007703:Peptidyl-Dipeptidase A; D000077583:Quinapril; D001920:Bradykinin