Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses.
Role of endothelium-derived relaxing factor in regulation of renal hemodynamic responses.
复制标题
内皮源性舒张因子在调节肾血流动力学反应中的作用。
作者：
J. P. Tolins;R. Palmer;S. Moncada;L. Raij
内皮来源的松弛因子（EDRF）最近被确定为一氧化氮（NO），起源于内皮细胞的l -精氨酸代谢。体外研究表明，EDRF/NO刺激可溶性鸟苷酸环化酶，增加血管平滑肌细胞中鸟苷3′，5′-环单磷酸（cGMP）水平，导致内皮依赖性血管扩张剂如乙酰胆碱（ACh）的血管松弛作用。EDRF/NO在正常生理或疾病状态中的重要性仍不确定。因此，我们研究了麻醉大鼠体内乙酰胆酸诱导的血流动力学反应、EDRF/NO合成与尿cGMP排泄率变化之间的关系。静脉输注乙酰胆碱导致低血压，维持肾小球滤过率和肾脏血管扩张。乙酰胆碱诱导尿cGMP排泄量呈剂量依赖性增加，而等剂量的内皮非依赖性血管扩张剂前列环素没有观察到这种作用。cGMP排泄率与乙酰胆碱引起的全身血压下降显著相关。ng -单甲基- l-精氨酸（L-NMMA）是一种l-精氨酸酶促合成一氧化氮的抑制剂，用它治疗可以阻止乙酰胆碱引起的尿cGMP排泄增加以及乙酰胆碱对全身和肾脏血流动力学的影响。血浆心房钠肽水平在乙酰胆碱输注后无明显变化。静脉输注L-NMMA与血压升高和尿cGMP基础排泄率降低相关。这种高血压作用被l -精氨酸逆转。（摘要删节250字）
An endothelium-derived relaxing factor (EDRF) has recently been identified as nitric oxide (NO), originating from endothelial cell metabolism of L-arginine. In vitro studies suggest that EDRF/NO stimulates soluble guanylate cyclase and increases guanosine 3',5'-cyclic monophosphate (cGMP) levels in vascular smooth muscle cells, resulting in the vasorelaxant effects of endothelium-dependent vasodilators such as acetylcholine (ACh). The importance of EDRF/NO in normal physiology or disease states remains uncertain. We therefore investigated the relationship between ACh-induced hemodynamic responses, synthesis of EDRF/NO, and changes in the rate of urinary cGMP excretion in the anesthetized rat in vivo. Intravenous infusion of ACh resulted in hypotension, maintenance of glomerular filtration rate, and renal vasodilatation. ACh induced a dose-dependent increase in urinary cGMP excretion, an effect that was not observed with equihypotensive doses of the endothelium-independent vasodilator, prostacyclin. Rates of cGMP excretion were significantly correlated with the fall in systemic blood pressure induced by ACh. Treatment with NG-monomethyl-L-arginine (L-NMMA), an inhibitor of enzymatic synthesis of nitric oxide from L-arginine, prevented the ACh-induced increase in urinary cGMP excretion as well as the systemic and renal hemodynamic effects of ACh. Plasma levels of atrial natriuretic peptide were unchanged by ACh infusion. Intravenous infusion of L-NMMA was associated with increased blood pressure and decreased basal rates of urinary cGMP excretion. This hypertensive effect was reversed by administration of L-arginine.(ABSTRACT TRUNCATED AT 250 WORDS)