Hashimoto K, Makino S, Hirasawa R, Takao T, Sugawara M, Murakami K, Ono K, Ota Z
Third Department of Internal Medicine, Okayama University Medical School, Japan.
Endocrinology. 1989 Sep;125(3):1161-7. doi: 10.1210/endo-125-3-1161.
Abnormalities in the hypothalamo-pituitary-adrenal axis in spontaneously hypertensive rats (SHR) during development of hypertension were investigated using in vivo and in vitro methods. Plasma ACTH responses to hemorrhage and ether stress were significantly smaller in 7-week-old SHR than in age-matched Wistar-Kyoto rats (WKY), while plasma corticosterone baseline levels and its response to stress were greater in SHR than in WKY. There was no significant difference in the plasma ACTH response to ether stress between bilaterally adrenalectomized SHR and WKY replaced with a 25% corticosterone pellet for 6 days. Adrenalectomy prevented the development of hypertension in SHR; however, corticosterone replacement restored hypertension. Plasma ACTH showed a smaller response to iv CRH injection in SHR than in WKY, while the ACTH response to arginine vasopressin was not different between SHR and WKY. CRH concentrations in the median eminence, posterior pituitary, and cerebral cortex were lower in SHR than in WKY, while the CRH concentration in the median eminence was not different in SHR and WKY when they were adrenalectomized with or without corticosterone replacement. Basal in vitro CRH release from hypothalamic tissue was reduced in SHR, while CRH release in response to 56 mM KCl was not different in SHR and WKY. These results suggest that adrenocortical function is enhanced in young SHR, that reduced ACTH response to stress and exogenous CRH in SHR may be ascribed to higher plasma corticosterone levels, and that corticosterone is essential for the development of hypertension in SHR.
采用体内和体外方法，研究了自发性高血压大鼠（SHR）在高血压发展过程中下丘脑 - 垂体 - 肾上腺轴的异常情况。7周龄的SHR对出血和乙醚应激的血浆促肾上腺皮质激素（ACTH）反应明显小于年龄匹配的Wistar - Kyoto大鼠（WKY），而SHR的血浆皮质酮基线水平及其对应激的反应则高于WKY。双侧肾上腺切除的SHR和用25%皮质酮丸剂替代6天的WKY对乙醚应激的血浆ACTH反应无显著差异。肾上腺切除术可预防SHR高血压的发展；然而，皮质酮替代可恢复高血压。SHR对静脉注射促肾上腺皮质激素释放激素（CRH）的血浆ACTH反应小于WKY，而SHR和WKY对精氨酸加压素的ACTH反应无差异。SHR中正中隆起、垂体后叶和大脑皮质的CRH浓度低于WKY，而双侧肾上腺切除且有或无皮质酮替代的SHR和WKY中正中隆起的CRH浓度无差异。SHR下丘脑组织的基础体外CRH释放减少，而SHR和WKY对56 mM氯化钾的CRH释放无差异。这些结果表明，幼年SHR的肾上腺皮质功能增强，SHR中对应激和外源性CRH的ACTH反应降低可能归因于较高的血浆皮质酮水平，并且皮质酮对于SHR高血压的发展至关重要。
