Salidiuretic action of the calcium antagonist nitrendipine in dogs.
In an attempt to define the effects of a calcium antagonist, nitrendipine, on renal function, intrarenal hemodynamics, and renin release, we infused the drug into the renal artery of anesthetized dogs. Infusion of nitrendipine at a rate of 5 micrograms/min in both hydropenic and hydrated dogs resulted in a significant increase in renal blood flow (RBF), glomerular filtration rate (GFR), urine flow and renin release, with no change in systemic blood pressure, indicating a significant renal vasodilation. The urinary excretion rate of sodium increased by the same proportion as that of calcium. The intrarenal blood flow as measured by hydrogen washout rate showed that the outer cortical flow increased by the same proportion as the inner cortical flow. During nitrendipine infusion, free water reabsorption rate (TcH2O) in hydropenic dogs or free water clearance (CH2O) in hydrated dogs increased in proportion to the urine flow. Neither the ratio of TcH2O nor that of CH2O to osmolar clearance changed throughout the experiment. These data suggest that nitrendipine may not inhibit sodium transport in the medullary portion of the ascending limb of Henle and may induce an enhancement of the delivery of sodium to the Henle loop. Thus, nitrendipine exerts its diuretic and natriuretic actions via the alteration of renal hemodynamic and the inhibitory effect on proximal sodium reabsorption.
Fukui
K
K
Department of Pharmacology, Kagawa Medical School, Japan.
Tamaki
T
T
Yamamoto
A
A
Shoji
T
T
Fujisawa
Y
Y
Iwao
H
H
Abe
Y
Y
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D003681:Dehydration / Q000503:physiopathology; D004231:Diuresis / Q000187:drug effects*; D004285:Dogs; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D007672:Kidney Cortex / Q000098:blood supply; D008297:Male; D009568:Nitrendipine / Q000494:pharmacology*; D009994:Osmolar Concentration; D012079:Renal Circulation / Q000187:drug effects; D012083:Renin / Q000097:blood
D009568:Nitrendipine; D012083:Renin