Effects of the calcium antagonist manidipine on renal hemodynamics and function in dogs: comparison with nifedipine.
The renal effects of manidipine, a new dihydropyridine calcium antagonist, were compared with those of nifedipine in anesthetized dogs. Intrarenal administration of manidipine 1 and 5 micrograms/kg resulted in prolonged (120 min) increases in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow (UF), and urinary excretion of electrolytes. In contrast, the renal effects of nifedipine disappeared within 5 to 10 min after administration. These results demonstrate that manidipine is a long-acting calcium antagonist. Manidipine proportionally increased RBF and GFR. As a result, filtration fraction was kept constant. The changes in afferent and efferent arteriolar resistance suggested that manidipine increases GFR via dilation of afferent arterioles with subsequent elevation of filtration pressure in the glomeruli. Manidipine also proportionally increased Tc H2O and Cosm; Tc H2O/Cosm did not change throughout the experiments. In addition, manidipine increased the fractional excretion of sodium from the distal tubule which was calculated from the lithium and sodium clearance. The mode of diuretic action of manidipine most likely involves inhibition of sodium reabsorption in the proximal and distal tubules, except the medullary portion of the ascending limb of Henle. The renal vascular site of action of manidipine might be the afferent arteriole.
He
H
H
Department of Pharmacology, Kagawa Medical School, Japan.
Tamaki
T
T
Aki
Y
Y
Kiyomoto
H
H
Iwao
H
H
Miyatake
A
A
Abe
Y
Y
D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007668:Kidney / Q000098:blood supply / Q000187:drug effects / Q000502:physiology*; D008094:Lithium / Q000652:urine; D008297:Male; D009543:Nifedipine / Q000494:pharmacology*; D009578:Nitrobenzenes; D010879:Piperazines; D012079:Renal Circulation / Q000187:drug effects*; D012964:Sodium / Q000652:urine; D014556:Urine
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine; D008094:Lithium; D012964:Sodium; D009543:Nifedipine