Effects of MPC-1304, a novel calcium antagonist, on stroke-prone spontaneously hypertensive rats.
The effects of MPC-1304, a newly developed 1,4-dihydropyridine derivative, on blood pressure and hypertensive complications in stroke-prone spontaneously hypertensive rats fed a high-salt diet (0.8% NaCl), were investigated. The antihypertensive effectiveness of nicardipine was used for the purpose of comparison. MPC-1304 and nicardipine were added to the diet, in doses of 0.01% (0.01% MPC-1304 diet), 0.03% (0.03% MPC-1304 diet) and 0.1% (0.1% nicardipine diet), respectively, throughout the experimental period (8 to 30 weeks of age). This chronic ingestion of MPC-1304 and nicardipine inhibited the development of hypertension and reduced the concentration of blood urea nitrogen, creatinine, triglyceride and total cholesterol in serum. Treatment with MPC-1304 inhibited the incidence of cerebral stroke, cardiac fibrosis, proliferative and fibrinoid arteriolitis and malignant nephrosclerosis. There was no significant difference in the antihypertensive effectiveness between 0.01% MPC-1304 and 0.1% nicardipine diets. Thus, MPC-1304 had antihypertensive effects in stroke-prone spontaneously hypertensive rats.
Department of Pharmacology, Nagasaki University School of Medicine, Japan.
M
M
Niwa
K
K
Shigematsu
T
T
Maeda
M
M
Fujimoto
K
K
Yamashita
Y
Y
Kataoka
K
K
Taniyama
D000284:Administration, Oral; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D001806:Blood Urea Nitrogen; D001921:Brain / Q000187:drug effects / Q000473:pathology; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D002561:Cerebrovascular Disorders / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D003404:Creatinine / Q000097:blood; D004032:Diet; D004095:Dihydropyridines / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D005355:Fibrosis / Q000517:prevention & control; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000150:complications / Q000188:drug therapy*; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000473:pathology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009400:Nephrosclerosis / Q000517:prevention & control; D009529:Nicardipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
D002121:Calcium Channel Blockers; D004095:Dihydropyridines; C059427:aranidipine; D002784:Cholesterol; D003404:Creatinine; D009529:Nicardipine