Depression in Na-free contracture in aorta isolated from SHR chronically treated with SM-6586

• Published in: Japanese Journal of Pharmacology 1992, Vol.58 (suppl.1), p.229-229
• Main Authors: Tsuyoshi Noguchi, Emiko Yoshida, Takashi Maniwa, Akira Miyagishi, Youichi Hara
• Format: Article
• Language: Japanese
• ISSN: 0021-5198

This study characterized force development in response to Na-free solution in isolated aortic strips from spontaneously hypertensive rats (SHR) chronically treated with SM-6586, a novel dihydropyridine Ca antagonist. Contractile response of SHR aortic strips to Na-free solution was greater than that of Wistar-Kyoto rats (WKY) aortic strips not only at the early stage of hypertension (11-weeks-old) but also at the prehypertensive stage (6-weeks-old). Oral administration of SM-6586 (5 mg/kg/day) to 11-weeks-old SHR for 4 weeks showed little effect on blood pressure and nicardipine (30 mg/kg/day) showed a sustained antihypertensive effect. In aorta from SM-6586 treated SHR, the force development in response to Na-free solution was significantly depressed , whereas that was not depressed in aorta from nicardipine treated SHR. SM-6586 inhibited dose-dependently 5-(N,N-hexamethylene) amiloride-sensitive intracellular alkalinization after acid loading in vascular smooth muscle cells (VSMC), which was caused by activation of Na/H antiporter, and this effect was more potent than that of nicardipine. These results suggest that the suppression of sodium accumulation in VSMC as a result of inhibition of Na/H antiporter might be involved in the depression in Na-free contracture in aorta from SHR treated with SM-6586.