Effect of beta-adrenoceptor antagonist and angiotensin-converting enzyme inhibitor on hypertension-associated changes in adenylyl cyclase type V messenger RNA expression in spontaneously hypertensive rats.
Adenylyl cyclase (AC) messenger RNA (mRNA) expression is decreased in failing hearts. Diminished expressions are accompanied by desensitization of beta-adrenergic signal transduction. Factors contributing to such changes in mRNA expression for the major myocardial isoform AC V are not well established. To assess the contributions of hypertension, left ventricular hypertrophy (LVH), the renin-angiotensin-aldosterone system (RAS), and the sympathetic nervous system to these changes, ventricular expression of AC V mRNA was measured at different ages in spontaneously hypertensive rats (SHRs). In addition, the effects on them of angiotensin-converting enzyme inhibitor and beta-adrenoceptor antagonists were determined. Prior to quantitative Northern blotting at ages 5, 9, or 12 weeks, hemodynamic and morphologic variables were measured in SHRs and Wistar-Kyoto rats (WKYs). The SHRs and WKYs were treated with an angiotensin-converting enzyme inhibitor, enalapril (10 mg/kg/d), or a beta(1)-adrenoceptor antagonist, atenolol (100 mg/kg/d), for 8 weeks preceding Northern analysis. Myocardial AC V mRNA expression increased from 5-12 weeks in both SHRs and WKYs. Expression of AC V mRNA in SHRs increased somewhat less than in WKYs at 9 weeks and significantly less at 12 weeks. This was accompanied by development of LVH and hypertension in SHRs. Blood pressure and left ventricular weight relative to body weight were markedly decreased by enalapril and were moderately decreased by atenolol. Expression of AC V mRNA in SHRs at 12 weeks was normalized equally by enalapril and atenolol to the level of WKYs. Thus AC V mRNA expression increases are blunted in the early stages of LVH in SHRs under the influences of beta(1)-adrenergic signal transduction and the RAS.
Fujino
Takayuki
T
First Department of Internal Medicine, Asahikawa Medical Colloge, Asahikawa, Japan. ffuji42@asahikawa-med.ac.jp
Hasebe
Naoyuki
N
Kawabe
Jun-Ichi
J
Fujita
Masaaki
M
Fukuzawa
Jun
J
Tobise
Katsuyuki
K
Kikuchi
Kenjiro
K
D000262:Adenylyl Cyclases / Q000096:biosynthesis*; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000375:Aging; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology*; D015152:Blotting, Northern; D004656:Enalapril / Q000494:pharmacology*; D015870:Gene Expression; D006352:Heart Ventricles / Q000201:enzymology; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000201:enzymology* / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000150:complications / Q000201:enzymology / Q000503:physiopathology; D007527:Isoenzymes / Q000096:biosynthesis*; D008297:Male; D009206:Myocardium / Q000201:enzymology; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012084:Renin-Angiotensin System / Q000502:physiology
D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D007527:Isoenzymes; D012333:RNA, Messenger; D001262:Atenolol; D004656:Enalapril; D000262:Adenylyl Cyclases; C419510:adenylyl cyclase type V