Cardiovascular pharmacology of 3-n-butylphthalide in spontaneously hypertensive rats

Abstract

The hypotensive and vasorelaxant effects of 3-n-butylphthalide (BuPh) and its possible mechanisms of action were investigated in spontaneously hypertensive rats (SHR) for the first time. A 13-day intraperitoneal infusion of BuPh at doses of 2.0 and 4.0 mg/day produced a transient hypotensive effect while a dose of 0.5 mg/day showed a significant hypotensive effect only on day 12. BuPh at 0.5 mg/day had no effect on the plasma and tissue angiotensin converting enzyme (ACE) activities, or on the tissue lipid peroxidation index. BuPh relaxed endothelium-intact and denuded aortic rings precontracted with phenylephrine and KCl. N(G)-nitro-L-arginine methyl ester, an inhibitor of nitric oxide synthase, did not attenuate the vasorelaxant activity of BuPh. The cumulative concentration response curves of phenylephrine and Ca2+ (in CaCl2-free, high KCl medium) were non- competitively inhibited by BuPh. However, BuPh did not interfere with the caffeine-induced release of intracellular Ca2+. It appears that the vasorelaxant effect of BuPh could be attributed to the blockade of Ca2+ entry, possibly through voltage- and receptor-operated Ca2+ channels, thereby lowering the systolic blood pressure of SHR.