Norepinephrine-induced relaxations in rat aorta mediated by endothelial beta adrenoceptors. Impairment by ageing and hypertension.
The objective of the present work has been to analyze the influence of endothelium, ageing and hypertension in the norepinephrine (NE)-induced responses. For this purpose we used aortic rings from spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats of different ages. In rings with endothelium from 5-week-old WKY, cumulative addition of NE (0.01 and 0.1 microM) caused concentration-dependent contractions, whereas higher concentrations (1 and 10 microM) induced concentration-dependent relaxations. In 5-week-old SHR and 3-month-old WKY rats, these relaxant responses were observed only at 10 microM NE, and they disappeared in older animals from both strains. In endothelium denuded rings, NE induced only contractions, which were similar in WKY rats of different ages, but significantly increased in 6- and 12-month-old SHR. In both strains, the endothelium-dependent relaxant responses to NE were abolished by NG-nitro-L-arginine methyl ester and propranolol, but not modified by yohimbine or ouabain. Isoproterenol (0.01-10 microM) induced concentration-dependent vasodilation in rings from 5-week-old rats of both strains, precontracted with 1 microM NE. Isoproterenol-elicited responses were reduced by endothelium removal or by 0.1 mM NG-nitro-L-arginine methyl ester and abolished by 1 microM propranolol. These results suggest that: 1) in the aorta from young WKY and prehypertensive SHR rats, NE induces vasodilations mediated by activation of endothelial beta adrenoceptors and release of nitric oxide; 2) these responses are impaired during ageing and hypertension; and 3) there is an important negative endothelial modulation of NE-induced contraction in adult SHR rats.
Arribas
S
S
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma, Madrid, Spain.
Marín
J
J
Ponte
A
A
Balfagón
G
G
Salaices
M
M
D000375:Aging / Q000378:metabolism*; D000818:Animals; D001011:Aorta / Q000187:drug effects*; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000378:metabolism*; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine / Q000494:pharmacology*; D010042:Ouabain / Q000494:pharmacology; D011433:Propranolol / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011943:Receptors, Adrenergic, beta / Q000378:metabolism*; D015016:Yohimbine / Q000494:pharmacology
D011943:Receptors, Adrenergic, beta; D015016:Yohimbine; D010042:Ouabain; D001120:Arginine; D011433:Propranolol; D007545:Isoproterenol; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine