title: Attenuation of renovascular hypertension by cyclooxygenase-2 inhibitor partly through ANP release.
abstract: Angiotensin II (Ang II) is an important inflammatory mediator. Ang II induces cyclooxygenase-2 (COX-2) expression and prostaglandin F2α release followed by cardiac hypertrophy. Inhibition of COX-2 may modulate high blood pressure but controversy still exists. The aim of this study was to determine the role of COX-2 in the regulation of blood pressure and to define the mechanisms in two kidney one-clip hypertensive (2K1C) rats. Chronic treatment with nimesulide or NS-398 (5 mg/kg/day) for 3 weeks lowered high blood pressure and cardiac hypertrophy with decreased expression levels of cardiac hypertrophy markers [atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP)], Ang type 1 receptor, urotensin II, and urotensin II receptor in 2K1C rats. Plasma level of ANP was markedly increased and plasma levels of Ang II and aldosterone were decreased by treatment with nimesulide or NS-398. In both in vitro and in vivo experiments, nimesulide or NS-398 augmented ANP release in 2K1C rats. The inhibitory effect of NS-398 on blood pressure was attenuated by the pretreatment with natriuretic peptide receptor-A (NPR-A) antagonist (A71915, 30 μg/kg/day). These results suggest that chronic treatment with nimesulide or NS-398 attenuated hypertension and cardiac hypertrophy partly through ANP release in 2K1C rats.
authors.affiliation: Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Byung Mun
authors.initials: BM
authors.lastname: Park
authors.affiliation: Department of Pharmacology, Taishan Medical University, Shandong, China.
authors.forename: Shan
authors.initials: S
authors.lastname: Gao
authors.affiliation: Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea.
authors.forename: Seung Ah
authors.initials: SA
authors.lastname: Cha
authors.affiliation: Department of Physiology, Diabetic Research Center, Chonbuk National University Medical School, Jeonju, Republic of Korea. Electronic address: shkim@chonbuk.ac.kr.
authors.forename: Suhn Hee
authors.initials: SH
authors.lastname: Kim
mesh_terms: D000450:Aldosterone / Q000097:blood; D000804:Angiotensin II / Q000097:blood*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000097:blood*; D001794:Blood Pressure / Q000187:drug effects; D006332:Cardiomegaly / Q000097:blood / Q000188:drug therapy / Q000235:genetics / Q000473:pathology; D051546:Cyclooxygenase 2 / Q000096:biosynthesis* / Q000235:genetics; D052246:Cyclooxygenase 2 Inhibitors / Q000008:administration & dosage; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D006978:Hypertension, Renovascular / Q000097:blood / Q000188:drug therapy* / Q000235:genetics* / Q000503:physiopathology; D020097:Natriuretic Peptide, Brain / Q000097:blood; D009578:Nitrobenzenes / Q000008:administration & dosage; D051381:Rats; D013449:Sulfonamides / Q000008:administration & dosage
chemical_list: D052246:Cyclooxygenase 2 Inhibitors; D009578:Nitrobenzenes; D013449:Sulfonamides; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; C080955:N-(2-cyclohexyloxy-4-nitrophenyl)methanesulfonamide; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D051546:Cyclooxygenase 2; C012655:nimesulide
keywords: ANP; Angiotensin; Cyclooxygenase; NS-398; Nimesulide; Renal hypertension