[Alteration in relaxation of atypical beta-adrenergic but not beta-3 receptors in arterial hypertension in the rat].
The aim of this study was to investigate the involvement of beta 3-adrenoceptors (beta 3-AR) in hypertension. Aortic rings were isolated from 12 weeks old WKY (Wistar-Kyoto) and SHR (spontaneously hypertensive rat) rats. Rings were placed in organ baths and constricted with phenylephrine. Then, cumulative concentration-relaxation curves to the beta 3-AR agonists were constructed. In both strains, SR58611, a preferential beta 3-agonist, produced similar concentration-dependent relaxation. CGP 12177 (CGP), (a partial beta 3-AR and atypical beta-AR agonist with beta 1-/beta 2-AR antagonistic properties) produced similar relaxation in WKY (pD2 = 5.10 +/- 0.06; Emax = 54 +/- 2%; n = 6) and in SHR (pD2 = 4.98 +/- 0.02; Emax = 58 +/- 4%; n = 6). In WKY, relaxant response to CGP was not modified by nadolol (10 microM) or L-748.337 (3 microM) suggesting an atypical beta-AR activation. By contrast, in SHR, the effect of CGP was strongly decreased by 3 microM L-748.337 (Emax = 27.8 +/- 5.4%; n = 7; p < 0.05 vs CGP alone), suggesting a possible participation of beta 3-AR in CGP-induced relaxation. In order to investigate the role of endothelium in CGP-induced relaxation, experiments were performed in denuded aortic rings. In WKY, CGP-induced relaxation was not modified by endothelium removal, by contrast, this was greatly inhibited in SHR (Emax = 18.3 +/- 1.9%; n = 9; p < 0.05 vs CGP in intact aortic rings). Endothelium-independent relaxation to CGP was resistant to nadolol or L-748.337 treatment which seems to rule out the involvement of beta 1, beta 2 and beta 3-AR. Endothelium-independent relaxation to CGP was significantly reduced by SQ 22536 or MDL 12330A, non-selective adenylyl cyclase inhibitors, indicating a role of cAMP-dependent pathway in CGP response. By contrast, the relaxant effect to CGP was not modified by SQ 22536 in SHR. In conclusion, these results show that [1] functional response to beta 3-AR stimulation was not altered in hypertension [2]. CGP activated an atypical beta-AR distinct from beta 1, beta 2 and beta 3-AR, partly through cAMP-dependent pathway. Impaired atypical beta-AR relaxation to CGP in SHR could contribute to the pathogenesis of the hypertension.
D000818:Animals; D046508:Culture Techniques; D004730:Endothelium, Vascular / Q000502:physiology; D006973:Hypertension / Q000503:physiopathology* / Q000662:veterinary; D051381:Rats; D011918:Rats, Inbred SHR; D011943:Receptors, Adrenergic, beta / Q000502:physiology*; D022702:Receptors, Adrenergic, beta-3 / Q000502:physiology*
D011943:Receptors, Adrenergic, beta; D022702:Receptors, Adrenergic, beta-3
Altération de la relaxation beta-adrénergique atypique non beta 3 dans l'hypertension artérielle chez le rat.