Bugajski J, Gadek-Michalska A, Głód R, Borycz J
Department of Physiology, Institute of Pharmacology, Polish Academy of Sciences, Kraków.
J Physiol Pharmacol. 1998 Dec;49(4):617-26.
In the present study the role of endogenous nitric oxide (NO) in the vasopressin-induced ACTH and corticosterone secretion was investigated in conscious rats. Vasopressin (AVP 5 microg/kg i.p.) considerably augmented ACTH and corticosterone secretion. L-arginine (120 and 300 mg/kg i.p.) did not significantly alter the AVP-induced secretion of those hormones. Nitric oxide synthase (NOS) blockers N(omega)-nitro-L-arginine (L-NNA) and its methyl ester (L-NAME) given i.p. 15 min before AVP markedly increased the AVP-induced ACTH secretion. L-NNA (2 mg/kg) more potently and significantly increased the AVP-induced ACTH secretion, whereas L-NAME elicited a weaker and not significant effect. Both those NOS antagonists intensified significantly and to a similar extent the AVP-induced corticosterone secretion. L-arginine (120 mg/kg i.p.) reversed the L-NNA-induced rise in the AVP-stimulated ACTH secretion and substantially diminished the accompanying corticosterone secretion. Neither vasopressin alone nor in combination with L-arginine and L-NAME evoked any significant alterations in the hypothalamic noradrenaline and dopamine levels. L-NNA (2 and 10 mg/kg i.p.) elicited a dose dependent and significant decrease in the hypothalamic noradrenaline level. The hypothalamic dopamine level was not significantly altered by any treatment. These results indicate that in conscious rats endogenous NO has an inhibitory influence on the AVP-induced increase in ACTH and corticosterone secretion. L-NNA is significantly more potent than L-NAME in increasing the AVP-induced ACTH secretion. This may be connected with a considerable increase by L-NNA of hypothalamic noradrenergic system activation which stimulates the pituitary-adrenal axis in addition to specific inhibition of NOS.
在本研究中，我们在清醒大鼠中研究了内源性一氧化氮（NO）在血管加压素诱导的促肾上腺皮质激素（ACTH）和皮质酮分泌中的作用。血管加压素（AVP，5微克/千克，腹腔注射）显著增加了ACTH和皮质酮的分泌。L-精氨酸（120和300毫克/千克，腹腔注射）并未显著改变AVP诱导的这些激素的分泌。在AVP注射前15分钟腹腔注射一氧化氮合酶（NOS）抑制剂N（ω）-硝基-L-精氨酸（L-NNA）及其甲酯（L-NAME），显著增加了AVP诱导的ACTH分泌。L-NNA（2毫克/千克）更有效地且显著增加了AVP诱导的ACTH分泌，而L-NAME的作用较弱且不显著。这两种NOS拮抗剂均显著且在相似程度上增强了AVP诱导的皮质酮分泌。L-精氨酸（120毫克/千克，腹腔注射）逆转了L-NNA诱导的AVP刺激的ACTH分泌增加，并显著减少了伴随的皮质酮分泌。单独的血管加压素或与L-精氨酸和L-NAME联合使用，均未引起下丘脑去甲肾上腺素和多巴胺水平的任何显著变化。L-NNA（2和10毫克/千克，腹腔注射）引起下丘脑去甲肾上腺素水平呈剂量依赖性的显著降低。任何处理均未显著改变下丘脑多巴胺水平。这些结果表明，在清醒大鼠中，内源性NO对AVP诱导的ACTH和皮质酮分泌增加具有抑制作用。在增加AVP诱导的ACTH分泌方面，L-NNA比L-NAME显著更有效。这可能与L-NNA除了特异性抑制NOS外，还大量增加下丘脑去甲肾上腺素能系统激活有关，而下丘脑去甲肾上腺素能系统激活会刺激垂体-肾上腺轴。
