Effects of benidipine, a long-acting calcium antagonist, on renal functions in anaesthetized spontaneously hypertensive rats.
1. The effects of benidipine, a long-acting calcium antagonist, on renal functions were determined in anaesthetized spontaneously hypertensive rats (SHR), as compared with those of amlodipine. 2. Benidipine at 3 and 10 mu g/kg (i.v.) significantly increased urine volume, sodium (Na) and potassium (K) excretions with no change in creatinine clearance (C-CRE). The increase in K excretion was relatively slight. Benidipine increased p-amino-hippuric acid clearance (C-PAH) without any change in C-CRE and, thus, decreased filtration fraction (FF). 3. On the other hand, amlodipine at 300 mu g/kg (i.v.) significantly increased Na and K excretions, but did not change FF. 4. Thus benidipine, but not amlodipine, can dilate glomerular efferent arteriole as well as afferent arteriole in SHR. It is, therefore, expected that benidipine would not induce intraglomerular hypertension, which could result in the progression of glomerular injury. 5. Benidipine at 3 mu g/kg (i.v.) increased lithium clearance, while it decreased CRE concentration and increased Na concentration in the stop-flow urine from the distal tubule. 6. These results suggest that benidipine produces diuresis by the inhibition of water and Na reabsorption at both the proximal and the distal tubules.
Nomura
H
H
Department of Pharmacology, Pharmaceutical Research Laboratories, Kyowa Hakko Kogyo Co., Ltd., Nagaizumi-cho, Sunto-gun, Shizuoka, Japan.
Kusaka
H
H
Karasawa
A
A
D017311:Amlodipine / Q000494:pharmacology; D000758:Anesthesia; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D004231:Diuresis / Q000187:drug effects; D007668:Kidney / Q000187:drug effects*; D007677:Kidney Function Tests; D008094:Lithium / Q000378:metabolism; D008297:Male; D009318:Natriuresis / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D017311:Amlodipine; C061004:benidipine; D008094:Lithium