title: Effects of quinapril on expression of eNOS, ACE, and AT1 receptor in deoxycorticosterone acetate-salt hypertensive rats.
abstract: Angiotensin II and nitric oxide (NO) may play a role in hypertensive cardiovascular remodeling. We evaluated the effects of long-term treatment with quinapril, an angiotensin converting enzyme (ACE) inhibitor, on expression of endothelial NO synthase (eNOS), ACE, and angiotensin II type 1 (AT1) receptor in the left ventricle and evaluated these relations to myocardial remodeling in deoxycorticosterone acetate (DOCA)-salt hypertensive rats. Deoxycorticosterone acetate-salt rats were induced with weekly injections of DOCA (30 mg/kg) and 1% saline in drinking water after right nephrectomy. Quinapril (DOCA-QUI, 10 mg/kg/day, subdepressor dose) or AT1 receptor antagonist TCV-116 (DOCA-TCV, 5 mg/kg/day, subdepressor dose) or vehicle (DOCA-V) were given after induction of DOCA-salt hypertension for 5 weeks, and age-matched sham-operated rats (ShC) served as a control group. The eNOS expression in the left ventricle were significantly decreased in DOCA-V compared with ShC, and were significantly increased in DOCA-QUI and DOCA-TCV compared with ShC and DOCA-V. The gene expression of ACE, AT1 receptor, and type I collagen mRNA were significantly increased in DOCA-V compared with ShC, and significantly suppressed in DOCA-QUI compared with DOCA-V. The DOCA-V rats demonstrated a significant increase of the wall-to-lumen ratio, perivascular fibrosis, and myocardial fibrosis, with all these parameters being significantly improved by quinapril. Myocardial remodeling in DOCA-salt hypertensive rats was significantly ameliorated by a subdepressor dose of quinapril, which may be due to an increase in eNOS mRNA and protein expression and a decrease in ACE and AT1 receptor mRNA expression in the left ventricle.
authors.affiliation: Department of Medicine, Dokkyo University School of Medicine, Mibu, Tochigi, Japan.
authors.forename: K
authors.initials: K
authors.lastname: Hara
authors.forename: N
authors.initials: N
authors.lastname: Kobayashi
authors.forename: S
authors.initials: S
authors.lastname: Watanabe
authors.forename: Y
authors.initials: Y
authors.lastname: Tsubokou
authors.forename: H
authors.initials: H
authors.lastname: Matsuoka
mesh_terms: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D001835:Body Weight / Q000187:drug effects; D003900:Desoxycorticosterone; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D007546:Isoquinolines / Q000494:pharmacology*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D019001:Nitric Oxide Synthase / Q000235:genetics / Q000378:metabolism*; D052250:Nitric Oxide Synthase Type III; D009929:Organ Size / Q000187:drug effects; D007703:Peptidyl-Dipeptidase A / Q000235:genetics / Q000378:metabolism*; D000077583:Quinapril; D012333:RNA, Messenger / Q000037:antagonists & inhibitors / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000235:genetics / Q000378:metabolism*; D012965:Sodium Chloride; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles; D016277:Ventricular Function, Left; D020257:Ventricular Remodeling
chemical_list: D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007546:Isoquinolines; D012333:RNA, Messenger; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D044005:Tetrahydroisoquinolines; D013777:Tetrazoles; D003900:Desoxycorticosterone; D012965:Sodium Chloride; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D007703:Peptidyl-Dipeptidase A; C077793:candesartan cilexetil; D000077583:Quinapril