Organ-protecting and life span-prolonging action of pranidipine in stroke-prone spontaneously hypertensive rats (SHR-SP)

• Published in: Japanese Journal of Pharmacology 2001, Vol.85 (suppl.1), p.103-103
• Main Authors: Toyoki Mori, Shokei Kim, Makoto Ohura, Takumi Sumida, Kiyotaka Toide, Masami Kishi, Yoshihide Miyazaki, Hiromichi Takase, Hiroshi Iwao
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

Pranidipine, a long-lasting 1,4-dihydropyridine calcium channel blocker, enhances nitric oxide-induced vascular relaxation in contrast to amlodipine, a compound in the same class. Pranidipine and amlodipine, administered at 1 and 2.5 mg/kg once daily, respectively, to SHR-SP, inhibited an increase in blood pressure and brain and ventricular weight. Pranidipine and amlodipine improved the histopathological scores of the brain (thrombosis and softening), heart (myocardial fibrosis), and kidney (proliferative vasculitis, tubular atrophy, tubular hyalinosis, interstitial cell infiltration, and fibrosis). In addition to these, pranidipine significantly reduced the coronary arterial wall thickening score. Pranidipine and amlodipine significantly lowered plasma creatinine, blood urea nitrogen, plasma renin activity, and plasma aldosterone, and decreased urinary protein and albumin excretion. In the survival study, half the animals were dead at 75, 70, and 25 weeks after once-daily administration of 1 mg/kg pranidipine, 2.5 mg/kg amlodipine, and vehicle, respectively. In conclusion, long-term treatment of SHR-SP with pranidipine protects target organs such as the brain, heart, and kidney and prolongs life span.