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. 1988 Sep;95(1):241–251. doi: 10.1111/j.1476-5381.1988.tb16570.x

Role of stimulatory GTP-binding protein (Gs) in reduced beta-adrenoceptor coupling in the femoral artery of spontaneously hypertensive rats.

M Asano 1, K Masuzawa 1, T Matsuda 1
PMCID: PMC1854152  PMID: 2464385

Abstract

1. Arterial relaxant responses to beta-adrenoceptor agonists are decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). To establish which component of the beta-adrenoceptor.adenylate cyclase (AC) system is impaired in the SHR arteries, effects of two activators of AC--cholera toxin (CTX) and forskolin--and of dibutyryl cyclic AMP (db cyclic AMP) were compared between strips of femoral arteries isolated from 13 week-old SHR and age-matched WKY. 2. In the absence of timolol, a beta-adrenoceptor antagonist, contractile responses of the strips to noradrenaline (NA) were significantly greater in the SHR than in the WKY. Timolol augmented the contractile responses to NA to a smaller extent in the SHR than in the WKY. 3. After blockade by timolol of beta-adrenoceptors, contractile responses of the strips to NA through the activation of alpha-adrenoceptors were not significantly different between the two strains. 4. Pre-treatment of the strips with CTX, an activator of the stimulatory GTP-binding protein (Gs), produced a slow-onset and long-lived antagonism of the alpha-adrenoceptor-mediated contractions. The antagonism was much smaller in the SHR than in the WKY. 5. The dose-response curves of the strips from both strains for alpha-adrenoceptor stimulation with NA determined after pretreatment with CTX were comparable to those determined in the absence of timolol. 6. Forskolin, an activator of the catalytic subunit of AC, and DB cyclic AMP also antagonized the alpha-adrenoceptor-mediated contractions. However, these antagonisms were not significantly different between the two strains. 7. Isobutyl methylxanthine (IBMX), an inhibitor of cyclic AMP phosphodiesterase, produced a similar antagonism of the alpha-adrenoceptor-mediated contractions between the two strains. 8. These results suggest that a reduced function of Gs is the main factor responsible for the decreased responsiveness to beta-adrenoceptor stimulation in the SHR femoral artery.

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Selected References

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