Antihypertensive and diuretic effects of YM-09730-5, a new calcium antagonist, in stroke-prone spontaneously hypertensive rats.
1. Effects of consecutive administration of YM-09730-5, (3S)-1-benzyl-3-pyrrolidinyl-methyl (4S)-2,6-dimethyl-4-(m-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxy lat e hydrochloride, a new calcium antagonist, for 9 wk on blood pressure and urinary excretion of electrolytes were studied in stroke-prone spontaneously hypertensive (SHRSP) rats. 2. YM-09730-5 (1 and 3 mg/kg per day, p.o.) prevented development of hypertension and produced a significant reduction in blood pressure from the first week of the experiment. Nicardipine (15 mg/kg per day, p.o.) produced almost the same degree of antihypertensive effect as YM-09730-5 at a dose of 3 mg/kg. 3. YM-09730-5 produced significant diuresis and increased urinary excretion of electrolytes throughout the experiment. 4. Chronic administration of YM-09730-5 (3 mg/kg) reduced the severity of glomerular lesions in the kidney and vasculitis in the mesenteric artery. 5. These results demonstrate that YM-09730-5 is a potential antihypertensive drug with a potency about 5 times higher than that of nicardipine.
Kawashima
K
K
Department of Pharmacology, Kyoritsu College of Pharmacy, Tokyo, Japan.
Toda
H
H
Oohata
H
H
Fujimoto
K
K
Suzuki
T
T
Inagaki
O
O
D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002561:Cerebrovascular Disorders / Q000235:genetics / Q000503:physiopathology*; D004231:Diuresis / Q000187:drug effects; D004232:Diuretics; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy / Q000235:genetics / Q000517:prevention & control; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000494:pharmacology; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D012083:Renin / Q000097:blood; D014563:Urodynamics / Q000187:drug effects
D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D004232:Diuretics; C050699:mepirodipine; D009529:Nicardipine; D012083:Renin; D009543:Nifedipine