Diuretic effect induced by intrarenal infusion of pinacidil in anesthetized dogs.
The diuretic action of pinacidil, a new vasodilating antihypertensive agent, was studied using anesthetized dogs. Intrarenally administered pinacidil (0.4, 2.0 and 10 micrograms/kg/min) produced a dose-related increase of renal blood flow, without altering mean arterial pressure. The glomerular filtration rate significantly increased only with the highest dosage. Pinacidil caused a dose-related augmentation of urine formation and, when given at 10 micrograms/kg/min, increased urine flow and urinary excretion of electrolytes to about 10 times and 3 to 9 times over the respective control value. In comparison, hydralazine (4.0 and 20 micrograms/kg/min) produced no significant diuretic action and bradykinin, given at a dose (0.02 micrograms/kg/min) equipotent to pinacidil (10 micrograms/kg/min) with respect to increasing renal blood flow, was less effective. Pinacidil administration significantly increased the fractional excretion of phosphate. Thus, pinacidil-induced diuresis seems to be due mainly to the vasodilating effect on renal vessels, with some contribution from an inhibitory effect on sodium reabsorption in the proximal tubules.
Morimoto
S
S
Department of Pharmacology, Osaka University of Pharmaceutical Sciences, Japan.
Matsumura
Y
Y
Sasaki
Y
Y
Takakuwa
T
T
Kageyama
M
M
D000758:Anesthesia; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000494:pharmacology; D004232:Diuretics / Q000008:administration & dosage / Q000494:pharmacology*; D004285:Dogs; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006830:Hydralazine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D007668:Kidney / Q000187:drug effects*; D010710:Phosphates / Q000378:metabolism; D020110:Pinacidil; D012079:Renal Circulation / Q000187:drug effects; D012964:Sodium / Q000378:metabolism; D014665:Vasodilator Agents / Q000494:pharmacology*
D004232:Diuretics; D006146:Guanidines; D010710:Phosphates; D014665:Vasodilator Agents; D006830:Hydralazine; D020110:Pinacidil; D012964:Sodium; D001920:Bradykinin; D007213:Indomethacin