Gardner D G, Schultz H D
Metabolic Research Unit, University of California, San Francisco 94143.
J Clin Invest. 1990 Jul;86(1):52-9. doi: 10.1172/JCI114714.
We have examined the effects of several PGs on the synthesis and release of the atrial natriuretic peptide (ANP) in vivo and in vitro. PGF2 alpha infusion in anesthetized rats resulted in a significant increase in plasma immunoreactive (ir) ANP levels in vivo despite effecting only modest changes in hemodynamics. The PGs were also effective at promoting irANP secretion in primary cultures of neonatal rat atrial and ventricular cardiocytes. PGF2 alpha increased irANP release with half-maximal induction seen at approximately 10(-8) M; PGE2 was somewhat less effective and prostacyclin (PGI2) was without effect. The PGs also increased ANP mRNA levels in these cells, suggesting that these agents exert a major effect on the synthesis as well as the secretion of the prohormone. Transient expression analysis of atrial cells transfected with 2,500 bp of human (h) ANP 5' flanking sequence linked to a chloramphenicol acetyltransferase (CAT) reporter demonstrated that PGF2 alpha (10(-5) M) increased hANP promoter activity approximately twofold relative to the control. PGF2 alpha had no effect on the promoterless control (pSV0-lamin CAT). Treatment of cultured atriocytes with high concentrations of a cyclooxygenase inhibitor resulted in a significant suppression of ANP secretion in vitro and a truncation of the plasma ANP response to volume infusion in vivo. Taken together these studies support a role for PGs as regulators of cardiac ANP synthesis and secretion, and suggest an additional mechanism whereby eicosanoids may act to control cardiovascular and renal homeostasis.
我们已经研究了几种前列腺素（PGs）在体内和体外对心房利钠肽（ANP）合成和释放的影响。在麻醉大鼠中输注前列腺素F2α（PGF2α），尽管对血流动力学仅有适度影响，但导致体内血浆免疫反应性（ir）ANP水平显著升高。PGs在促进新生大鼠心房和心室心肌细胞原代培养物中irANP分泌方面也有效。PGF2α增加irANP释放，在约10^(-8)M时出现半数最大诱导；前列腺素E2（PGE2）效果稍差，而前列环素（PGI2）无作用。PGs还增加了这些细胞中ANP mRNA水平，表明这些药物对前激素的合成以及分泌均有主要作用。用2500bp的人（h）ANP 5'侧翼序列与氯霉素乙酰转移酶（CAT）报告基因转染心房细胞的瞬时表达分析表明，PGF2α（10^(-5)M）相对于对照使hANP启动子活性增加约两倍。PGF2α对无启动子对照（pSV0-层粘连蛋白CAT）无作用。用高浓度环氧化酶抑制剂处理培养的心房细胞导致体外ANP分泌显著受抑制，以及体内血浆ANP对容量输注反应减弱。综上所述，这些研究支持PGs作为心脏ANP合成和分泌调节因子的作用，并提示类花生酸可能控制心血管和肾脏内环境稳定的另一种机制。
