Hashimoto T
Jpn J Pharmacol. 1980 Apr;30(2):173-86. doi: 10.1254/jjp.30.173.
Effects of intrarenal-arterial (i.r.a.) and intravenous (i.v.) infusions of PGE2, I2 and F2 alpha on systemic blood pressure (BP), heart rate (HR), renal blood flow (RBF), urine volume (UV), renal function and plasma renin activity (PRA) of the renal venous blood (RVPRA) were investigated. A dose-dependent fall in BP was observed with PGE2 and I2 and was accompanied by a tachycardia (PGE2 < I2, i.r.a. < i.v.). PGE2 and I2 induced increases in RBF and UV in a roughly dose-dependent manner (PGE2 > I2, i.r.a. > i.v.), however, antidiuresis was observed with the highest intravenously given dose of PGI2 (300 ng/kg/min) such being ascribed to a pronounced hypotension. Changes in electrolyte excretion induced by PGE2 and I2 were similar to the pattern of those in RBF or UV. Neither PGE2 or I2 produced any significant changes in the glomerular filtration rate (GFR). The diuretic effect of PGE2 and F2 alpha correlated with osmolar clearance (Cosm) (r = 0.89, p < 0.01; r = 0.55, p < 0.01) and free water clearance (CH2O) (r = 0.52, p < 0.01; r = 0.83, p < 0.01), whereas that of PGI2, only with Cosm (r = 0.74, p < 0.01). PGF2 alpha produced the weakest changes in the parameters described above. PGE2 and I2 (30 ng/kg/min, i.r.a.), but not PGF2 alpha, produced a significant elevation of RVPRA without any significant change in BP. These findings suggest that PGE2 plays a primary role in the kidney, whereas PGI2 is important in the regulation of the systemic circulation, and that PGE2, I2 and F2 alpha all have different modes of action in producing diuresis. Both PGE2 and I2 may participate in the control of renin secretion.
研究了肾内动脉(i.r.a.)和静脉(i.v.)输注前列腺素E2(PGE2)、前列腺素I2(I2)和前列腺素F2α(F2α)对全身血压(BP)、心率(HR)、肾血流量(RBF)、尿量(UV)、肾功能以及肾静脉血中血浆肾素活性(PRA)(RVPRA)的影响。观察到PGE2和I2可使血压呈剂量依赖性下降,并伴有心动过速(PGE2<I2,肾内动脉给药<静脉给药)。PGE2和I2大致呈剂量依赖性地使RBF和UV增加(PGE2>I2,肾内动脉给药>静脉给药),然而,静脉给予最高剂量的前列环素(PGI2)(300 ng/kg/min)时观察到抗利尿作用,这归因于明显的低血压。PGE2和I2引起的电解质排泄变化与RBF或UV的变化模式相似。PGE2和I2均未使肾小球滤过率(GFR)发生任何显著变化。PGE2和F2α的利尿作用与渗透清除率(Cosm)相关(r = 0.89,p<0.01;r = 0.55,p<0.01)以及自由水清除率(CH2O)相关(r = 0.52,p<0.01;r = 0.83,p<0.01),而PGI2的利尿作用仅与Cosm相关(r = 0.74,p<0.01)。PGF2α对上述参数产生的变化最弱。PGE2和I2(30 ng/kg/min,肾内动脉给药)可使RVPRA显著升高,而血压无任何显著变化,但PGF2α无此作用。这些发现表明,PGE2在肾脏中起主要作用,而PGI2在全身循环调节中很重要,并且PGE2、I2和F2α在产生利尿作用方面均具有不同的作用方式。PGE2和I2可能均参与肾素分泌的调控。