INVOLVEMENT OF CALCIUM CHANNELS IN FIBROBLAST GROWTH FACTOR-INDUCED ACTIVATION OF ARTERIAL CELLS IN SPONTANEOUSLY HYPERTENSIVE RATS

To gain insight into the mechanisms that could account for the abnorma l vascular structure in spontaneously hypertensive rats (SHR) and to d etermine whether this could be affected by calcium channel blockers, w e compared the influence of dihydropyridines on basic fibroblast growt h factor (bFGF)-induced DNA synthesis in cultured adventitial fibrobla sts isolated from SHR and Wistar-Kyoto rat (WKY) aorta. Our results sh owed that (a) bFGF was a potent mitogen for adventitial fibroblasts, m uch more active in SHR-derived than in WKY-derived cells, thus confirm ing the hyperreactivity of the SHR arterial cells; (b) the mitogenic p otency of bFGF could be reduced by dihydropyridines (rank order of pot ency was nifedipine approximate to nisoldipine > nitrendipine > nimodi pine); and (c) the nifedipine inhibitory effect could be completely an d partially antagonized in WKY- and SHR-derived fibroblasts, respectiv ely, by the calcium channel agonist Bay K 8644. Moreover, the extent o f nifedipine inhibitory extent increased and decreased in SHR- and WKY -derived fibroblasts, respectively, according to duration of treatment of cells with the drug, suggesting that SHR fibroblasts became progre ssively more sensitive whereas those of WKY became more refractory to the drug treatment. These data indicate that in aortic fibroblasts sti mulated by bFGF, L-type calcium channels participate in the antimitoti c effect of dihydropyridines and suggest the existence of interactions between these channels and the bFGF signaling pathways. They also sug gest that nifedipine inhibits bFGF-induced DNA synthesis by different mechanisms in SHR and WKY fibroblasts.