A forskolin derivative, colforsin daropate hydrochloride, inhibits the decrease in cortical renal blood flow induced by noradrenaline or angiotensin II in anesthetized rats.
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.
Department of Anesthesiology, University of Occupational and Environmental Health, School of Medicine, Kitakyushu, Japan.
Junichi
J
Ogata
Kouichiro
K
Minami
Kayoko
K
Segawa
Yasuhito
Y
Uezono
Munehiro
M
Shiraishi
Chikako
C
Yamamoto
Takeyoshi
T
Sata
Kim
K
Sung-Teh
Akio
A
Shigematsu
D000758:Anesthesia; D000804:Angiotensin II / Q000037:antagonists & inhibitors*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005576:Colforsin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D007672:Kidney Cortex / Q000098:blood supply*; D008297:Male; D009638:Norepinephrine / Q000037:antagonists & inhibitors*; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D014662:Vasoconstrictor Agents / Q000037:antagonists & inhibitors*
D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C122001:colforsin daropate; D005576:Colforsin; D009638:Norepinephrine