Attenuation of hypertension, cardiomyocyte hypertrophy, and myocardial fibrosis by beta-adrenoceptor blockers in rats under long-term blockade of nitric oxide synthesis.
The effects of propranolol and atenolol were investigated on arterial hypertension, cardiomyocyte hypertrophy, and ventricular ischaemic lesions induced by an 8-week treatment with the nitric oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME; 20 mg/rat per day) in Wistar rats. Propranolol and atenolol (30 mg/rat per day each) were given in the drinking water concomitantly to L-NAME. Treatment with L-NAME induced marked arterial hypertension and cardiomyocyte hypertrophy, both of which were significantly reduced by propranolol and atenolol. A marked repairing fibrosis was also observed in L-NAME-treated rats and this was significantly attenuated in animals receiving the beta-blockers. In L-NAME group, 33% mortality was observed, whereas all the animals from the other groups survived. Our study demonstrates that propranolol and atenolol reduce arterial hypertension, cardiomyocyte hypertrophy and myocardial fibrosis induced by L-NAME, suggesting that beta-blockers are of beneficial value in treatment of vascular and cardiac alterations caused by chronic nitric oxide deficiency.
Pacca
Sandra R M C
SR
Department of Pharmacology, Faculty of Medical Sciences, Institute of Biology, UNICAMP, Campinas, São Paulo, Brazil.
de Azevedo
Ana Paula
AP
De Oliveira
Claudia F
CF
De Luca
Iara M S
IM
De Nucci
Gilberto
G
Antunes
Edson
E
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001262:Atenolol / Q000494:pharmacology / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D004791:Enzyme Inhibitors; D005355:Fibrosis; D006321:Heart / Q000033:anatomy & histology / Q000187:drug effects; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000188:drug therapy* / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000172:deficiency; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D009929:Organ Size / Q000187:drug effects; D011433:Propranolol / Q000494:pharmacology / Q000627:therapeutic use*; D051381:Rats; D017208:Rats, Wistar; D013997:Time Factors
D058671:Adrenergic beta-1 Receptor Antagonists; D000319:Adrenergic beta-Antagonists; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D001262:Atenolol; D011433:Propranolol; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester