Hirata Y, Matsuoka H, Kimura K, Sugimoto T, Hayakawa H, Suzuki E, Sugimoto T
Second Department of Internal Medicine, University of Tokyo, Japan.
J Cardiovasc Pharmacol. 1991;17 Suppl 7:S169-71. doi: 10.1097/00005344-199100177-00047.
It has been suggested that endothelin (ET) induces the release of endothelium-derived relaxing factor (EDRF). To explore the possible modification of ET-induced renal vasoconstriction by EDRF, we examined the effects of ET on renal vascular resistance (RVR) and urinary Na excretion (UNaV) in the rat isolated perfused kidney before and after the administration of EDRF antagonists. ET at 2 x 10(-11) to 2 x 10(-9) M elevated the RVR in a dose-dependent fashion, whereas it lowered the RVR at 10(-12) M. ET decreased UNaV significantly only at the highest dose. Acetylcholine at 10(-7) M decreased the RVR (-19%, p less than 0.05) and increased UNaV (+177%, p less than 0.05). In contrast, a soluble guanylate cyclase inhibitor, methylene blue (MB; 10(-5) M), increased the RVF by 30% (p less than 0.05) and decreased UNaV by 48% (p less than 0.05). Pretreatment with MB significantly augmented the ET-induced renal vasoconstriction by about 80%. However, UNaV was not influenced significantly. ET increased the urinary excretion of prostaglandin (PG) E2 and 6-keto-PGF1 alpha. Pretreatment with indomethacin (10(-5) M) also significantly enhanced the response of RVR to ET by 60% without changing UNaV. These results suggest that the vasoconstrictor, but not the antinatriuretic, activity of ET may be modified by the release of EDRF and prostacyclin.
有人提出内皮素（ET）可诱导内皮源性舒张因子（EDRF）的释放。为了探究EDRF对ET诱导的肾血管收缩的可能调节作用，我们在给予EDRF拮抗剂前后，检测了ET对大鼠离体灌注肾脏肾血管阻力（RVR）和尿钠排泄（UNaV）的影响。2×10⁻¹¹至2×10⁻⁹M的ET以剂量依赖性方式升高RVR，而10⁻¹²M的ET则降低RVR。ET仅在最高剂量时显著降低UNaV。10⁻⁷M的乙酰胆碱降低RVR（-19%，p<0.05）并增加UNaV（+177%，p<0.05）。相比之下，可溶性鸟苷酸环化酶抑制剂亚甲蓝（MB；10⁻⁵M）使RVF增加30%（p<0.05）并使UNaV降低48%（p<0.05）。MB预处理显著增强ET诱导的肾血管收缩约80%。然而，UNaV未受到显著影响。ET增加前列腺素（PG）E2和6-酮-PGF1α的尿排泄。吲哚美辛（10⁻⁵M）预处理也显著增强RVR对ET的反应60%，而不改变UNaV。这些结果表明，ET的血管收缩活性而非利钠活性可能受到EDRF和前列环素释放的调节。
