Effects of quinapril on expression of eNOS, ACE, and AT1 receptor in deoxycorticosterone acetate-salt hypertensive rats

• Published in: American journal of hypertension 2001-04, Vol.14 (4), p.321-330
• Main Authors: Hara, Kazuyoshi, Kobayashi, Naohiko, Watanabe, Shigeko, Tsubokou, Yusuke, Matsuoka, Hiroaki
• Format: Article
• Language: English
• Subjects: angiotensin II; Angiotensin Receptor Antagonists; Angiotensin-converting enzyme inhibitor; Angiotensin-Converting Enzyme Inhibitors - pharmacology; Animals; Antihypertensive agents; Antihypertensive Agents - pharmacology; Benzimidazoles - pharmacology; Biological and medical sciences; Biphenyl Compounds - pharmacology; Body Weight - drug effects; Cardiovascular system; Desoxycorticosterone; gene expression; Hemodynamics - drug effects; hypertension; Hypertension - chemically induced; Hypertension - metabolism; Hypertension - pathology; Hypertension - physiopathology; Isoquinolines - pharmacology; Medical sciences; Myocardium - metabolism; Myocardium - pathology; nitric oxide synthase; Nitric Oxide Synthase - genetics; Nitric Oxide Synthase - metabolism; Nitric Oxide Synthase Type III; Organ Size - drug effects; Peptidyl-Dipeptidase A - genetics; Peptidyl-Dipeptidase A - metabolism; Pharmacology. Drug treatments; Quinapril; Rats; Rats, Wistar; Receptor, Angiotensin, Type 1; Receptor, Angiotensin, Type 2; Receptors, Angiotensin - genetics; Receptors, Angiotensin - metabolism; RNA, Messenger - antagonists & inhibitors; RNA, Messenger - metabolism; Sodium Chloride; Tetrahydroisoquinolines; Tetrazoles; Ventricular Function, Left; Ventricular Remodeling
• ISSN: 0895-7061; 1879-1905; 1941-7225
• DOI: 10.1016/S0895-7061(00)01283-8

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.