[Impairment of atypical beta-adrenergic-mediated relaxation in spontaneously hypertensive rats before and during the development of arterial hypertension].
The aims of this study was to characterize the functional response of atypical beta-adrenoceptors (beta-AR) in rat aorta and to investigate whether this relaxation was altered before and during the development of hypertension. Aortic rings from 4 or 12 weeks old Wistar Kyoto (WKY) rats or spontaneously hypertensive rats (SHR) were placed in organ baths and constricted with phenylephrine. Then, cumulative concentration-relaxation curves to the beta-AR agonists were constructed. In intact aortic rings from 12 weeks old WKY rats, CGP 12,177 (CGP) and cyanopindolol (partial beta 3-AR agonists and atypical beta-AR agonists with beta 1/beta 2-AR antagonist properties) produced concentration-dependent relaxation (pD2 = 5.09 +/- 0.03; Emax = 60.4 +/- 2.5%; n = 9; pD2 = 6.17 +/- 0.05; Emax = 95.9 +/- 1%; n = 5 respectively). The endothelium removal did not modify this relaxation. In 12 weeks old WKY rats, the endothelium-independent relaxation to CGP was not modified in the presence of nadolol (beta 1/beta 2-AR antagonist) or L-748 337 (beta 3-AR antagonist) excluding the participation of beta 1, beta 2 et beta 3-AR in this effect. By contrast, this relaxation was significantly inhibited by CGP 20712A or bupranolol, atypical beta-AR antagonists at high concentrations. In 12 weeks old SHR, endothelium-independent relaxation to CGP or cyanopindolol was greatly inhibited. In order to sought out whether impairment of atypical beta-AR-mediated relaxation was due to hypertension, experiments were performed in 4 weeks old SHR. At this age, CGP-induced relaxation was greatly inhibited compared to that obtained in age-matched WKY rats. In 12 weeks old SHR pretreated with pertussis toxin (10 micrograms/kg i.p./3 days), the relaxant effect to CGP was partly restored. We conclude that the atypical beta-AR were functionally expressed in aortic vascular smooth muscle cells of rat aorta. In 4 or 12 weeks old SHR rats, atypical beta-AR-mediated relaxation was impaired, suggesting that this dysfunction occurs before the establishment of hypertension. Gi proteins may be one of the factors that contributes to this impairment.
Mallem
Y
Y
Unité de pharmacologie fonctionnelle UPSP 5304 Ecole nationale vétérinaire de Nantes.
Gogny
M
M
Gautier
F
F
Bucas
V
V
Desfontis
J Cl
JC
D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D001011:Aorta / Q000502:physiology*; D004730:Endothelium, Vascular / Q000502:physiology*; D006973:Hypertension / Q000503:physiopathology*; D011412:Propanolamines / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D017208:Rats, Wistar; D011943:Receptors, Adrenergic, beta / Q000502:physiology*
D000318:Adrenergic beta-Agonists; D011412:Propanolamines; D011943:Receptors, Adrenergic, beta; C033394:CGP 12177