Effects of the new calcium antagonist 2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate on cerebral circulation in cats

Effects of CD-349 (2-nitratopropyl 3-nitratopropyl 2,6-dimethyl-4-(3-nitrophenyl)-1,4-dihydropyridine-3,5-dicarboxylate) on cerebral circulation were studied in 10 cats. The cats were fixed in a stereotactic head-holder, and two burr holes were made at 3-mm intervals over the left parietal cortex. Through one cranial window, the pial artery and vein diameters were measured continuously by a newly developed videocamera system in conjuction with a width analyzer, and the other one was used for measurement of cerebral blood volume (CBV). The pial artery (141 ± 14 μm) was dilated by 16.6 ± 4.9% (p < 0.01) 1 min and 24.8 ± 5.1% (p < 0.01) 5 min after the CD-349 injection. The pial vein (101 ± 20 μm) was also dilated with the percent increase of the diameter being 11.4 ± 4.0% (p < 0.01) 1 min and 11.3 ± 4.9% (p < 0.05) 5 min after the CD-349 administration. The CBV was also increased. The mean arterial blood pressure was decreased by 39.8 ± 7.3 mmHg (p < 0.01) 1 min and 34.4 ± 5.5 mmHg (p < 0.01) 5 min after drug injection. Thereafter, the blood pressure gradually returned to the pre-drug level. From these results it is suggested that CD-349 exerts direct vasodilatory action via inhibition of calcium influx across vascular cell membranes into cerebral vessels.