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C Gauthier

Publications and source records attributed to C Gauthier.

120 records · Page 7Linked to original sources
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[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.

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[Vascular beta-adrenergic remodeling in rat transgenic model over-expressing endothelial beta3-adrenoceptors].

In rat thoracic aorta, the stimulation of endothelial beta3-adrenoceptors (beta-AR) produces a vasorelaxation through activation of a NO synthase pathway and an increase in cGMP levels. In hypertension, a global decrease of the beta-AR response has been described. In spontaneously hypertensive rats (SHR), we have shown that beta3-adrenoceptor-mediated relaxation was not modified in SHR aorta at the age of 12 weeks, in spite of an upregulation of beta3-adrenoceptors. In order to determine the consequences of an over-expression of the beta3-AR, we have developed a transgenic rat over-expressing specifically in endothelial cells the human beta3-AR (Tg beta3). By real-time quantitative PCR, we have determined the expression level of the different beta-AR subtypes. We confirmed an over-expression of the beta3-AR transcripts in Tg beta3 (ratio = 3.39 +/- 0.8; n=3 for Tg beta3 vs wild type [WT] animals). Surprisingly, we observed in Tg beta3 a decrease of beta1-AR transcripts (ratio = 0.76 +/- 0.03; n=3 for Tg beta3 vs WT animals) and no variation for beta2-AR transcripts (ratio = 1.95 +/- 0.60; n=3 for Tg beta3 vs WT animals). In aorta rings from WT and Tg beta3, the isoproterenol-induced relaxation was similar (WT: Emax = 82 +/- 6%, n=6; Tg beta3: Emax = 85 +/- 6, n=6). By contrast, in the presence of 10 microM nadolol, a beta1-, beta2-AR antagonist, the isoproterenol-induced response was significantly increased in Tg beta3 (WT: Emax = 68 +/- 6%, n=6: Tg beta3: Emax = 86 +/- 3; p < 0.01 vs WT). This effect was loss on denuded aortic rings. In conclusion, our study reported similar results to those obtained in hypertension in which a decrease of the beta-AR expression was associated to an elevation of the beta3-AR density. Moreover, this over-expression in our transgenic model is associated to a potential response induced by beta3-AR. Therefore, an activation of beta3-AR could supply the beta1- / beta2-AR decrease. Then, our transgenic model should be used to characterize the physiological consequences of this over-expression as well as to determine the putative involvement of this receptor in the pathogenesis of hypertension.

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