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The effects of cinnarizine, Ca2+-antagonist, on the antihypertensive effect of coadministered beta-blockers, propranolol and metoprolol, were investigated in SHR. Drugs were coadministered orally for 4 weeks. Hemodynamic and biochemical changes induced by above drugs were determined to elucidate their mechanism of action. a) Cardiohypertropy of SHR was significantly improved by the treatment of beta-blockers as well as combination with cinnarizine and beta-blockers. b) Mg2+-contents were increased in ventricle and decreased in plasma and aorta in all of the groups, especially in the group of propranolol with cinnarizine. c) c-GMP contents in ventricle were increased when cinnarizine was coadministered with propranolol, and c-GMP contents in aorta were increased when cinnarizine was coadministered with metoprolol, camparing with propranolol or metoprolol alone-treated group. d) Plasma renin activity appeared to be increased in cinnarizine treated alone, but reduced by combination with beta-blockers. e) Triglycerides and Na+ contents in serum were decreased in the group of metoprolol with cinnarizine, comparing with metoprolol alone-treated group. Increased K+ and Ca2+ excretions in urine by beta-blockers were inhibited by cinnarizine, so Na+/K+ excretion ratios were increased. Diuretic effects was showed in metoprolol alone treated group, but reduced when coadministered with cinnarizine.
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