Anand-Srivastava M B
Clinical Research Institute of Montreal, Quebec, Canada.
Biochem Pharmacol. 1988 Aug 1;37(15):3017-22. doi: 10.1016/0006-2952(88)90291-2.
Adenylate cyclase activity was studied in the myocardial sarcolemma and aorta of spontaneously-hypertensive rats (SHR) and their respectively Wistar-Kyoto (WKY) controls. Basal enzyme activity was decreased in the SHR as compared to the WKY group. Adenylate cyclase stimulation by N-ethylcarboxamide adenosine (NECA) was significantly lower in the myocardial sarcolemma and aorta of SHR, and this decreased responsiveness was associated with a reduction in the Vmax. Other agonists, such as isoproterenol (ISO), epinephrine, dopamine (DA), and glucagon, also enhanced myocardial adenylate cyclase activity to various degrees in SHR and WKY, but stimulation (Vagonists/Vbasal) was always lower in the SHR. NaF and forskolin (FSK), which activate adenylate cyclase via receptor-independent mechanisms, augmented it in the myocardial sarcolemma of SHR to a lesser extent than in WKY. While the guanine nucleotides GTP and GMP-P(NH)P elevated adenylate cyclase in a concentration-dependent manner in both SHR and WKY, the magnitude of stimulation was significantly lower in the former group. Decreased basal adenylate cyclase activity and responsiveness to adenosine, various hormones, NaF and FSK were observed in SHR of all ages, i.e. from 4 to 24 weeks of age. In addition, basal, hormone-, NaF- and FSK-stimulated adenylate cyclase activity was diminished markedly in the aorta of SHR. These results suggest that, in SHR, not only is basal adenylate cyclase activity decreased but the abilities of adenosine, other hormones and agonists, such as NaF and FSK, to stimulate adenylate cyclase, guanine nucleotide regulatory protein and the catalytic subunit of the cyclase system are also impaired in the myocardial sarcolemma and aorta.
对自发性高血压大鼠（SHR）及其相应的Wistar-Kyoto（WKY）对照大鼠的心肌肌膜和主动脉中的腺苷酸环化酶活性进行了研究。与WKY组相比，SHR的基础酶活性降低。在SHR的心肌肌膜和主动脉中，N-乙基甲酰胺腺苷（NECA）对腺苷酸环化酶的刺激作用明显较低，这种反应性降低与Vmax的降低有关。其他激动剂，如异丙肾上腺素（ISO）、肾上腺素、多巴胺（DA）和胰高血糖素，也在不同程度上增强了SHR和WKY心肌中的腺苷酸环化酶活性，但SHR中的刺激作用（激动剂/基础值）总是较低。通过不依赖受体的机制激活腺苷酸环化酶的氟化钠（NaF）和福斯高林（FSK），在SHR心肌肌膜中的增强程度低于WKY。虽然鸟嘌呤核苷酸GTP和GMP-P（NH）P在SHR和WKY中均以浓度依赖性方式提高腺苷酸环化酶活性，但前一组中的刺激幅度明显较低。在所有年龄段（即4至24周龄）的SHR中均观察到基础腺苷酸环化酶活性降低以及对腺苷、各种激素、NaF和FSK的反应性降低。此外，SHR主动脉中的基础、激素、NaF和FSK刺激的腺苷酸环化酶活性明显降低。这些结果表明，在SHR中，不仅基础腺苷酸环化酶活性降低，而且腺苷、其他激素和激动剂（如NaF和FSK）刺激腺苷酸环化酶、鸟嘌呤核苷酸调节蛋白和环化酶系统催化亚基的能力在心肌肌膜和主动脉中也受到损害。
