| Budget Amount *help |
¥2,300,000 (Direct Cost: ¥2,300,000)
Fiscal Year 1997: ¥1,100,000 (Direct Cost: ¥1,100,000)
Fiscal Year 1996: ¥1,200,000 (Direct Cost: ¥1,200,000)
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| Research Abstract |
Effects of calcium antagonists on the mechanical responses of isolated dog artery strips to the direct vasoconstrictor (prostaglandin F_<2alpha>), EDRF releaser (substance P) and nerve stimulation were examined. Contraction induced by prostaglandin F_<2alpha> was inhibited by nicardipine (L-type calcium channnel inhibitor), flunarizine and AE0047 (a new dihydropyridine derivative), but not by omega-conotoxin (N-type channel inhibitor). Endothelium-dependent relaxation caused by substance P was not suppressed by nicardipine, omega-conotoxin nor tetramethrin (T-type channel inhibitor). Perivascular nerve stimulation produced relaxations in the cerebral artery whereas contractions in the mesenteric artery ; the relaxation and contraction were abolished by nitric oxide (NO) synthase inhibitors and alpha-adrenoceptor antagonists, respectively, indicating that neurotransmitters mainly released from the cerebral and mesenteric arteries are NO and noradrenaline, respectively. Nicardipine and t
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etramethrin did not affect the neurogenic relaxation in the cerebral artery, but omega-conotoxin, flunarizine and AE0047 inhibited the relaxation. Although contractions induced by nerve stimulation and noradrenaline were suppressed by both AE0047 and nicardipine, noradrenaline release caused by nerve stumulation was not inhibited by nicardipine but by AE0047. Cadmium, a non-selective calcium antagonist, inhibited the mechanical responses to prostaglandin F_<2alpha>, substance P and nerve stimulation. These results indicate that calcium influx is mainly regulated by L-type channel in the vascular smooth muscles and by N-type channel in the perivascular nerves, but that in the endothelial cells has not been determined since specific L-, N- and T-type calcium channel inhibitors failed to inhibit the calcium-dependent endothelial function. Suppression by flunarizine, but not by nicardipine, of the neurogenic cerebroarteial relaxation may explain its anti-migraine action. Further, it is found that some of the new dehydropyridine derivatives possess not only direct vasodilator action but also inhibitory action on sympathetic nerve function. Involvement of calcium/calmodulin-dependent protein kinase II in the production of neural NO has also been suggested. Less
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