Ogata Junichi, Minami Kouichiro, Segawa Kayoko, Uezono Yasuhito, Shiraishi Munehiro, Yamamoto Chikako, Sata Takeyoshi, Sung-Teh Kim, Shigematsu Akio
Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Nephron Physiol. 2004;96(2):p59-64. doi: 10.1159/000076409.
A forskolin derivative, colforsin daropate hydrochloride (CDH), acts directly on adenylate cyclase to increase the intracellular cyclic adenosine monophosphate levels which produce a positive inotropic effect and a lower blood pressure. However, little is known about the effects of CDH on the renal function. We used laser Doppler flowmetry to measure the cortical renal blood flow (RBF) in male Wistar rats given a continuous intravenous infusion of CDH and evaluated the effects of CDH on the noradrenaline (NA) and angiotensin II (AngII) induced increases in blood pressure and reductions in RBF. Continuous intravenous administration of CDH at 0.25 microg/kg/min did not affect the mean arterial pressure (MAP), but increased heart rate and RBF. Continuous intravenous administration of CDH at high doses (0.5-0.75 microg/kg/min) decreased the MAP, with little effect on the RBF. The administration of exogenous NA (1.7 microg/kg) increased the MAP and decreased the RBF. However, a bolus injection of NA did not decrease the RBF during continuous intravenous administration of CDH, and CDH did not affect the NA-induced increase in MAP. The administration of exogenous AngII (100 ng/kg) increased MAP and decreased RBF and heart rate, but a bolus injection of AngII did not decrease RBF during continuous intravenous administration of CDH. These results suggest that CDH plays a protective role against the pressor effects and the decrease in RBF induced by NA or AngII.
一种福斯可林衍生物,盐酸可乐福辛(CDH),直接作用于腺苷酸环化酶以提高细胞内环磷酸腺苷水平,从而产生正性肌力作用并降低血压。然而,关于CDH对肾功能的影响知之甚少。我们使用激光多普勒血流仪测量连续静脉输注CDH的雄性Wistar大鼠的肾皮质血流量(RBF),并评估CDH对去甲肾上腺素(NA)和血管紧张素II(AngII)诱导的血压升高和RBF降低的影响。以0.25微克/千克/分钟的速度连续静脉注射CDH对平均动脉压(MAP)没有影响,但会增加心率和RBF。高剂量(0.5 - 0.75微克/千克/分钟)连续静脉注射CDH会降低MAP,对RBF影响较小。静脉注射外源性NA(1.7微克/千克)会升高MAP并降低RBF。然而,在连续静脉注射CDH期间推注NA不会降低RBF,并且CDH不影响NA诱导的MAP升高。静脉注射外源性AngII(100纳克/千克)会升高MAP并降低RBF和心率,但在连续静脉注射CDH期间推注AngII不会降低RBF。这些结果表明,CDH对NA或AngII诱导的升压作用和RBF降低具有保护作用。