前列腺素合成抑制剂对血管紧张素II和III诱导的醛固酮释放的抑制作用。
Attenuation of angiotensin II- and III-induced aldosterone release by prostaglandin synthesis inhibitors.
作者信息
Campbell W B, Gomez-Sanchez C E, Adams B V, Schmitz J M, Itskovitz H D
出版信息
J Clin Invest. 1979 Dec;64(6):1552-7. doi: 10.1172/JCI109615.
The effect of two prostaglandin synthesis inhibitors, indomethacin and meclofenamate, on angiotensin II (AII)- and III (AIII)-induced aldosterone release was studied in normal and sodium-depleted conscious rats and in adrenal capsular cell suspensions obtained from normal rats. In normal rats, in vivo AII and AIII were equipotent in causing dose-related increases in serum aldosterone concentrations. Indomethacin decreased the basal serum aldosterone levels by 50% and serum renin levels by 43%. In addition, the steroidogenic effects of AII and AIII were reduced by 45 and 63% with 3 mg/kg of indomethacin and 63 and 73% with 10 mg/kg, respectively. In contrast, meclofenamate failed to alter basal serum levels of aldosterone or AII-stimulated aldosterone release but inhibited serum renin levels by 27% and the aldosterone-stimulating effect of AIII by 99%. Indomethacin (3 mg/kg) and meclofenamate (2 mg/kg) inhibited urinary prostaglandin (PG)E(2) and PGF(2alpha) excretion by 63 and 52% and 37 and 31%, respectively. Both inhibitors significantly decreased the adrenal capsular PGE(2) and PGF(2alpha) content and the conversion of [(14)C]arachidonate to [(14)C]PGE(2) and [(14)C]PGF(2alpha). In sodium-depleted rats, indomethacin produced similar effects reducing the control serum aldosterone levels by 29%, AII-stimulated aldosterone by 47%, and completely suppressing the aldosterone response to AIII without altering serum renin activity. In adrenal cell suspensions, similar results were observed with indomethacin inhibiting basal and AII- and AIII-stimulated aldosterone release by 29, 81, and 93%, respectively. Meclofenamate failed to alter basal and AII-stimulated aldosterone release but inhibited that stimulated by AIII by 86%. The present findings suggest that prostaglandins modulate the effects of the renin-angiotensin system by stimulating the release of renin from the kidney and augmenting the steroidogenic effects of AII and AIII in the adrenal cortex.
在正常和缺钠的清醒大鼠以及从正常大鼠获取的肾上腺皮质细胞悬液中，研究了两种前列腺素合成抑制剂吲哚美辛和甲氯芬那酸对血管紧张素II（AII）和III（AIII）诱导的醛固酮释放的影响。在正常大鼠中，体内AII和AIII在引起血清醛固酮浓度呈剂量相关增加方面具有同等效力。吲哚美辛使基础血清醛固酮水平降低50%，血清肾素水平降低43%。此外，3mg/kg吲哚美辛使AII和AIII的类固醇生成作用分别降低45%和63%，10mg/kg吲哚美辛则分别降低63%和73%。相比之下，甲氯芬那酸未能改变基础血清醛固酮水平或AII刺激的醛固酮释放，但使血清肾素水平降低27%，并使AIII刺激的醛固酮作用降低99%。吲哚美辛（3mg/kg）和甲氯芬那酸（2mg/kg）分别使尿前列腺素（PG）E2和PGF2α排泄量降低63%和52%以及37%和31%。两种抑制剂均显著降低肾上腺皮质PGE2和PGF2α含量以及[14C]花生四烯酸向[14C]PGE2和[14C]PGF2α的转化。在缺钠大鼠中，吲哚美辛产生类似作用，使对照血清醛固酮水平降低29%，AII刺激的醛固酮降低47%，并完全抑制对AIII的醛固酮反应，而不改变血清肾素活性。在肾上腺细胞悬液中，观察到类似结果，吲哚美辛分别使基础以及AII和AIII刺激的醛固酮释放降低29%、81%和93%。甲氯芬那酸未能改变基础和AII刺激的醛固酮释放，但使AIII刺激的醛固酮释放降低86%。目前的研究结果表明，前列腺素通过刺激肾脏释放肾素以及增强肾上腺皮质中AII和AIII的类固醇生成作用来调节肾素 - 血管紧张素系统的作用。
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