Anti-atherogenic Effect of Ca²⁺-Antagonists

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Recently it has been reported that Ca²⁺-antagonists suppressed the experimental atherosclerosis caused by high cholesterol diet. And it is suggested that the calcium metabolism in the arterial wall may be involved in the initiation and the development of arteriosclerosis. In order to investigate whether Ca²⁺-antagonists can also suppress another experimental model of arteriosclerosis, we employed the method of placing a polystyrene cuff around the common carotid artery of rabbits to cause an arteriosclerotic lesion, and applied this method to study the anti-arterioscle-rotic effect of Ca²⁺-antagonist, diltiazem and flunarizine.
We designed two experiments. In experiment I 20 rabbits were invested with cuffs in their right common carotid arteries and then divided into two groups, control group (n=10) and diltiazem group (n=10). In experiment II, 18 rabbits were treated similarly and divided into two groups, control group (n=9) and flunarizine group (n=9). Then a daily oral dose of 100mg/kg of diltiazem in the diltiazem group, and 5.7mg/kg of flunarizine in the flunarizine group were administered. After 21 days all the rabbits were sacrificed and their right common carotid arteries were excised and examined.
In both experiments intimal thickening was found over the segments invested with the cuff, and disruption of internal elastic lamina (I. E. L.) was also observed. Then the measurements of intimal thickness were carried out. The results showed that, in experiment I, although the mean value of the diltiazem group was somewhat lower than that of the control group, the difference was not significant, and in experiment II, there was no difference between the flunarizine group and the control group. The incidence of the disruption of the I. E. L. in each group was also examined. The incidence in diltiazem group was significantly lower than that in the control group, whereas there was no significant difference between flunarizine group and its control group. The reason why diltiazem suppressed the disruption of the I. E. L. seemed that it might improve the hemodynamic changes of the invested segments, or might prevent the increasing affinity of elastic fibers to calcium and inhibit elastolysis.
It was concluded that in this experimental model diltiazem was effective in inhibiting the disruption of the I. E. L., but not so effective in suppressing the intimal thickening, while flunarizine had no effect on these two findings.