Antihypertensive and diuretic effects of YM-09730-5, a new calcium antagonist, in stroke-prone spontaneously hypertensive rats

Gen Pharmacol. 1991;22(2):263-6. doi: 10.1016/0306-3623(91)90444-b.

Abstract

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.

MeSH terms

  • Animals
  • Antihypertensive Agents*
  • Blood Pressure / drug effects
  • Calcium Channel Blockers / pharmacology*
  • Cerebrovascular Disorders / genetics
  • Cerebrovascular Disorders / physiopathology*
  • Diuresis / drug effects
  • Diuretics*
  • Heart Rate / drug effects
  • Hypertension / drug therapy
  • Hypertension / genetics
  • Hypertension / prevention & control
  • Male
  • Nicardipine / pharmacology
  • Nifedipine / analogs & derivatives*
  • Nifedipine / pharmacology
  • Organ Size / drug effects
  • Rats
  • Rats, Inbred SHR
  • Renin / blood
  • Urodynamics / drug effects

Substances

  • Antihypertensive Agents
  • Calcium Channel Blockers
  • Diuretics
  • mepirodipine
  • Nicardipine
  • Renin
  • Nifedipine