Increased expression of endothelial nitric oxide synthase and caveolin-1 in the aorta of rats with isoproterenol-induced cardiac hypertrophy.
Isoproterenol-induced cardiac hypertrophy is associated with increased expression of endothelial nitric oxide synthase in the aorta but without signs of improved endothelial function. The aim was to examine the hypothesis that increased expression of eNOS allosteric inhibitor caveolin-1 could be associated with unimproved endothelium-dependent relaxations. Rats received isoproterenol (5 mg/kg body mass, i.p., n = 13) or its vehicle (n = 14) during 1 week. Systolic blood pressure (SBP) and heart rate (HR) were measured by the tail-cuff method. Expression of eNOS and caveolin-1 was measured using immunoblotting analysis. Relaxations of isolated aorta to acetylcholine and sodium nitroprusside were evaluated ex vivo. After 1 week of isoproterenol administration, basal SBP and HR were decreased (SBP 110 +/- 3 vs. 126 +/- 3 mmHg, p < 0.05; HR 342 +/- 8 vs. 366 +/- 6 beats/min, p < 0.05). Isoproterenol increased the mass of the left ventricle (+33% +/- 4% vs. control; p < 0.05) and right ventricle (+40% +/- 9%; p < 0.05). Isoproterenol administration increased the expression of eNOS (+53% +/- 12%; p < 0.05) and caveolin-1 (+54% +/- 20%, p < 0.05) in the aorta. Relaxation of isolated aorta to acetylcholine and sodium nitroprusside showed a trend towards a worsened endothelial function and a lower sensitivity to exogenous NO. Thus, 1 week of isoproterenol administration led to increased eNOS expression in the aorta without amelioration of endothelial vasorelaxation function. Concomitant increase in caveolin-1 expression may be responsible for this paradox.
Krenek
P
P
Department of Pharmacology and Toxicology, Faculty of Pharmacy, Comenius University, Odbojárov 10, 832 32 Bratislava, Slovak Republic. krenek@fpharm.uniba.sk
Klimas
J
J
Kroslakova
M
M
Gazova
A
A
Plandorova
J
J
Kucerova
D
D
Fecenkova
A
A
Svec
P
P
Kyselovic
J
J
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000378:metabolism* / Q000503:physiopathology; D001794:Blood Pressure; D006332:Cardiomegaly / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051242:Caveolin 1 / Q000096:biosynthesis*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate; D006352:Heart Ventricles / Q000473:pathology; D007545:Isoproterenol; D009569:Nitric Oxide / Q000378:metabolism; D052250:Nitric Oxide Synthase Type III / Q000096:biosynthesis*; D009599:Nitroprusside / Q000494:pharmacology; D009929:Organ Size; D051381:Rats; D017208:Rats, Wistar; D015854:Up-Regulation; D014664:Vasodilation; D014665:Vasodilator Agents / Q000494:pharmacology
D051242:Caveolin 1; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D007545:Isoproterenol; D000109:Acetylcholine