The effects of the new spasmolytic agent HA1077, which belongs to the calciumantagonists but acts by mechanisms different from those of conventional calcium channel blockers, on the cerebral microcirculation were studied in rats using isolated and cannulated intracerebral (parenchymal) arterioles of 50 microns average diameter. After the vessels had developed spontaneous tone, increasing concentrations of HA1077 were applied extraluminally. HA1077 induced vasodilation in a dose-dependent manner with a maximal increase of vessel diameter of 73.9 +/- 5.1% (mean +/- SEM, n = 5) at 10(-4) M and with half-maximal responses (ED50) of 1.00 x 10(-6) M. The extent of maximal vasodilation achieved by HA1077 was significantly greater than that induced by such conventional calcium channel blockers as diltiazem, verapamil, nifedipine and nimodipine (about 50% each in a previous report from our laboratory). Vasoconstriction induced by synthetic thromboxane A2 (10(-9) M to 10(-5) M) which is through to be highly dependent on intracellular calcium, was completely inhibited by 10(-4) M HA1077, whereas both verapamil and nimodipine at a concentration at maximal vasodilation effects (10(-5) M and 10(-7) M respectively) only partially inhibited such vasoconstriction. These results suggest that HA1077 may exert a more potent vasodilator effect on the cerebral microcirculation than do conventional calcium channel blockers.
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