Hayashi K, Loutzenhiser R, Epstein M, Suzuki H, Saruta T
Department of Internal Medicine, School of Medicine, Keio University, Tokyo, Japan.
Circ Res. 1994 Nov;75(5):821-8. doi: 10.1161/01.res.75.5.821.
Acetylcholine (ACh) elicits vasodilation by releasing a number of endothelium-derived relaxing factors (EDRFs). We used the isolated perfused hydronephrotic rat kidney to examine the characteristics of ACh-induced vasodilation of renal afferent arterioles during different types of underlying vasoconstriction. Basal arteriolar tone was increased by either elevating perfusion pressure to 180 mm Hg (myogenic), administering 0.3 mumol/L norepinephrine (NE), or elevating medium potassium concentration to 30 mmol/L (KCl). ACh (10 mumol/L) completely reversed myogenic and NE-induced vasoconstriction and reversed KCl-induced vasoconstriction by 80 +/- 5%. However, whereas ACh produced a sustained vasodilation during KCl- and NE-induced vasoconstriction, only a transient reversal of myogenic vasoconstriction was observed, and myogenic tone recovered within 5 to 10 minutes. ACh-induced vasodilation of arterioles preconstricted with KCl was markedly inhibited by either indomethacin (100 mumol/L) or nitro-L-arginine (100 mumol/L) and was completely abolished by pretreatment with both inhibitors. In contrast, indomethacin and nitro-L-arginine had no effect on the transient response to ACh observed during pressure-induced vasoconstriction. In vessels preconstricted with NE, nitro-L-arginine converted the normally sustained response to ACh to a transient vasodilation, which was refractory to both nitric oxide synthase and cyclooxygenase inhibition. Since this component was not observed during KCl-induced vasoconstriction, it may reflect the actions of an, as yet unidentified, endothelium-derived hyperpolarizing factor (EDHF). Our findings thus suggest that prostanoids, nitric oxide, and EDHF all contribute to ACh-induced renal afferent arteriolar vasodilation and that the relative contributions of these individual EDRFs depends on the nature of the underlying renal vascular tone.
乙酰胆碱（ACh）通过释放多种内皮源性舒张因子（EDRFs）引起血管舒张。我们使用离体灌注的肾积水大鼠肾脏，来研究在不同类型的基础血管收缩过程中，ACh诱导的肾传入小动脉血管舒张的特征。通过将灌注压力升高至180 mmHg（肌源性）、给予0.3 μmol/L去甲肾上腺素（NE）或将培养基钾浓度升高至30 mmol/L（KCl），可增加基础小动脉张力。ACh（10 μmol/L）可完全逆转肌源性和NE诱导的血管收缩，并使KCl诱导的血管收缩逆转80±5%。然而，尽管ACh在KCl和NE诱导的血管收缩过程中产生持续的血管舒张，但仅观察到肌源性血管收缩的短暂逆转，且肌源性张力在5至10分钟内恢复。吲哚美辛（100 μmol/L）或硝基-L-精氨酸（100 μmol/L）可显著抑制ACh诱导的预先用KCl收缩的小动脉的血管舒张，且两种抑制剂预处理可完全消除该作用。相比之下，吲哚美辛和硝基-L-精氨酸对压力诱导的血管收缩过程中观察到的ACh的短暂反应无影响。在用NE预先收缩的血管中，硝基-L-精氨酸将对ACh的正常持续反应转变为短暂的血管舒张，该反应对一氧化氮合酶和环氧化酶抑制均无反应。由于在KCl诱导的血管收缩过程中未观察到该成分，它可能反映了一种尚未确定的内皮源性超极化因子（EDHF）的作用。因此，我们的研究结果表明，前列腺素、一氧化氮和EDHF均有助于ACh诱导的肾传入小动脉血管舒张，且这些单个EDRFs的相对贡献取决于基础肾血管张力的性质。
