Effects of pinacidil on renal hemodynamics and function in anesthetized dogs.
We studied the effects of pinacidil on renal hemodynamics and function in anesthetized dogs. An intravenous injection of pinacidil, at a dose of 0.25 mg/kg, resulted in a rapid and marked reduction of the mean systemic blood pressure (MSBP) accompanied by a significant increase in renal blood flow (RBF). There were no significant changes in glomerular filtration rate (GFR), urine flow (UF) and urinary excretion of electrolytes (UEE). When pinacidil was administered at a dose of 0.5 mg/kg, the hypotensive effect was more potent. RBF did not change, but GFR, UF and UEE significantly decreased. These antidiuretic effects were not influenced by renal denervation. Hydralazine, at doses of 0.5 and 2.0 mg/kg, caused a significant and sustained reduction of MSBP, but the effects were much less potent than those seen with pinacidil. A sustained increase in RBF was observed after hydralazine at both doses. The lower dose elicited increases in UF and UEE, although the GFR remained unchanged. The higher dose of hydralazine caused a reduction of GFR, accompanied by decreases in UF and UEE. These antidiuretic effects were abolished by renal denervation. Intravenous injection of pinacidil or hydralazine produced a significant increase in the renin secretion rate. Intrarenal arterial infusion of pinacidil (2.0 micrograms/kg/min) produced a more marked diuretic effect than hydralazine (20 micrograms/kg/min). These findings indicated that the hypotensive activity of pinacidil is more potent than that of hydralazine, and suggested that the antidiuretic action of i.v. pinacidil (0.5 mg/kg) is due to a reduction of renal perfusion pressure. Furthermore, this drug may exert an additional action in the kidney to cause diuresis.
D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D003714:Denervation; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006146:Guanidines / Q000008:administration & dosage / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology; D007261:Infusions, Intra-Arterial; D007275:Injections, Intravenous; D007668:Kidney / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D020110:Pinacidil; D012079:Renal Circulation / Q000187:drug effects*; D012083:Renin / Q000378:metabolism; D014556:Urine; D014655:Vascular Resistance
D000959:Antihypertensive Agents; D006146:Guanidines; D006830:Hydralazine; D020110:Pinacidil; D012083:Renin