Asano M, Masuzawa K, Matsuda T, Asano T
Department of Pharmacology, Nagoya City University Medical School, Japan.
J Pharmacol Exp Ther. 1988 Aug;246(2):709-18.
Arterial relaxant responses to beta adrenoceptor agonists are decreased in spontaneously hypertensive rats (SHR) when compared with normotensive Wistar-Kyoto rats (WKY). To determine which component of the beta adrenoceptor-adenylate cyclase (AC) system is involved in the decreased beta adrenoceptor responses, effects of two activators of AC-forskolin and cholera toxin and of dibutyryl cyclic AMP (DBcAMP) were compared between the strips of femoral arteries isolated from 13-week-old SHR and age-matched WKY. Arterial relaxant responses to either forskolin, an activator of AC or DBcAMP were not significantly different between the SHR and WKY, whereas the relaxant responses to norepinephrine (NE) via beta adrenoceptors were significantly weaker in the SHR than in the WKY. In the absence of timolol, a beta adrenoceptor antagonist, contractile responses to NE were significantly greater in the SHR than in the WKY. Timolol augmented the contractile responses to NE to a greater extent in the WKY than in the SHR. After the blockade by timolol of beta adrenoceptors, contractile responses to alpha adrenoceptor stimulation with NE were not significantly different between the two strains. The pretreatment of the strips with cholera toxin, an activator of stimulatory GTP-binding protein (Gs), antagonized the alpha adrenoceptor-mediated contractions much greater in the WKY than in the SHR. The alpha adrenoceptor-mediated contractions after the pretreatment with cholera toxin were comparable to the contractile responses to NE determined in the absence of timolol in either the SHR or the WKY. Forskolin and DBcAMP also antagonized the alpha adrenoceptor-mediated contractions. However, these antagonisms were not significantly different between the two strains. The cellular cAMP content in arterial strips after the stimulation with NE was significantly less in the SHR than in the WKY, whereas the cAMP contents were similar in arterial strips from both strains which were stimulated with forskolin. These results suggest that the reduced function of Gs is involved in the abnormality of beta adrenoceptor-AC system in the SHR femoral artery.
与正常血压的Wistar-Kyoto大鼠（WKY）相比，自发性高血压大鼠（SHR）对β肾上腺素能受体激动剂的动脉舒张反应降低。为了确定β肾上腺素能受体-腺苷酸环化酶（AC）系统的哪个成分参与了β肾上腺素能受体反应的降低，比较了从13周龄的SHR和年龄匹配的WKY分离的股动脉条带对两种AC激活剂——福斯可林和霍乱毒素以及二丁酰环磷腺苷（DBcAMP）的反应。SHR和WKY对AC激活剂福斯可林或DBcAMP的动脉舒张反应没有显著差异，而SHR中通过β肾上腺素能受体对去甲肾上腺素（NE）的舒张反应明显弱于WKY。在没有β肾上腺素能受体拮抗剂噻吗洛尔的情况下，SHR对NE的收缩反应明显大于WKY。噻吗洛尔在WKY中比在SHR中更大程度地增强了对NE的收缩反应。在用噻吗洛尔阻断β肾上腺素能受体后，两种品系对NE刺激α肾上腺素能受体的收缩反应没有显著差异。用刺激性GTP结合蛋白（Gs）激活剂霍乱毒素预处理条带后，WKY中α肾上腺素能受体介导的收缩比SHR中受到的拮抗作用更大。霍乱毒素预处理后的α肾上腺素能受体介导的收缩与在没有噻吗洛尔的情况下SHR或WKY中对NE的收缩反应相当。福斯可林和DBcAMP也拮抗α肾上腺素能受体介导的收缩。然而，这两种品系之间的这些拮抗作用没有显著差异。NE刺激后动脉条带中的细胞cAMP含量在SHR中明显低于WKY，而用福斯可林刺激的两种品系动脉条带中的cAMP含量相似。这些结果表明，Gs功能降低与SHR股动脉中β肾上腺素能受体-AC系统的异常有关。
