Nebivolol ameliorates nitric oxide deficient hypertension.
Nebivolol is a new selective beta 1-adrenoceptor antagonist with nitric oxide (NO)-releasing properties. In the present study we have analyzed whether nebivolol affects the development of the arterial hypertension that follows the chronic inhibition of nitric oxide synthesis. Nebivolol (1 mg/kg/day, 14 days) was given concurrently with the NO synthesis inhibitor Nw-nitro-L-arginine methyl ester (L-NAME, 0.1, 1, and 10 mg/kg/day, 14 days) to several groups of rats. Blood pressure, renal function, plasma renin activity (PRA), and NO activity and metabolites were measured at the end of the treatment period. L-NAME treatment alone increased mean arterial pressure dose dependently (103.5 +/- 2.4, 110.9 +/- 2.0, and 125.8 +/- 2.2 mmHg, respectively). Nebivolol completely prevented the development of arterial hypertension in the groups treated with L-NAME at the doses of 0.1 and 1 mg/kg/day and reduced the increase achieved with the L-NAME dose of 10 mg/kg/day (110.3 +/- 2.7). There were no differences in glomerular filtration rate or natriuresis between nebivolol-treated and -untreated rats. Plasma nitrates+nitrites and calcium-dependent NO synthase activity in the kidney also decreased dose dependently with L-NAME treatment and nebivolol did not significantly modify it. However, PRA was lower in all groups treated with nebivolol and L-NAME as compared to the rats receiving only L-NAME. These data indicate that nebivolol prevents the development of the arterial hypertension associated with chronic NO deficit and this effect seems to be dependent on the inhibition of renin-angiotensin system.
Fortepiani
Lourdes A
LA
Departamento de Fisiología, Facultad de Medicina, 30100 Murcia, Spain.
Ortíz
M Clara
MC
Atucha
Noemí M
NM
García-Estañ
Joaquín
J
D058671:Adrenergic beta-1 Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology / Q000627:therapeutic use; D001578:Benzopyrans / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D004983:Ethanolamines / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D000068577:Nebivolol; D009569:Nitric Oxide / Q000172:deficiency*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012084:Renin-Angiotensin System / Q000187:drug effects
D058671:Adrenergic beta-1 Receptor Antagonists; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004983:Ethanolamines; D000068577:Nebivolol; D009569:Nitric Oxide; D019331:NG-Nitroarginine Methyl Ester