title: OPC-13340, a new dihydropyridine calcium channel blocker attenuates rapid vascular smooth muscle cell growth in spontaneously hypertensive rats.
abstract: We investigated the mechanism of the antimitotic effects of calcium channel blockers in vascular smooth muscle cells (VSMC) from spontaneously hypertensive rats (SHR). VSMC from SHR exhibited rapid proliferation through a quick transition from the G0/G1 to the DNA synthetic (S) phase and from the S to the G2/mitotic (M) phase, whereas the DNA synthetic rate itself was equal to that of Wistar-Kyoto rats (WKY). OPC-13340, a new dihydropyridine calcium channel blocker, dose-dependently decreased incorporation of [3H]thymidine into the DNA fragments in randomly cycling VSMC in SHR. Cell cycle analysis showed that the rapid transition from the S to the G2/M period was restored by OPC-13340 to the control level in WKY, whereas the quick transition from G0/G1 to S was unaffected. This antimitotic effect of OPC-13340 was reflected by attenuation of enhanced cellular protein synthesis during the G2/M period. Protein synthesis in the G0/G1 period was not influenced by OPC-13340. Thus, these data indicate that the calcium channel blocker OPC-13340 mitigates the enhanced proliferation observed in randomly cycling VSMC from SHR and that this effect is primarily due to normalization of the premature mitosis during the G2/M period.
mesh_terms: D000818:Animals; D001013:Aorta, Thoracic / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D002478:Cells, Cultured; D004247:DNA / Q000378:metabolism; D004261:DNA Replication / Q000187:drug effects; D004095:Dihydropyridines / Q000494:pharmacology*; D004591:Electrophoresis, Polyacrylamide Gel; D009131:Muscle, Smooth, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY
chemical_list: D002121:Calcium Channel Blockers; D004095:Dihydropyridines; D004247:DNA; C048161:pranidipine