Mechanism of action of the inhibitory effect of nifedipine on the growth of cultured aortic cells from spontaneously hypertensive and normotensive rats
Abstract
1. To gain insight into the parameters which control vascular structure, we investigated the mechanisms whereby nifedipine, and other dihydropyridines, inhibit the growth of cultured fibroblasts isolated from the adventitia of the aorta of spontaneously hypertensive (SHR) and normotensive Wistar Kyoto (WKY) rats. 2. The effects of nifedipine on cell proliferation and on serum-induced DNA synthesis were determined by measuring the cell number and the incorporation of [3H]-thymidine, respectively. The mechanism of action of nifedipine was studied by adding the drug either to randomly growing cells or to quiescent, G0/G1 arrested and synchronized cells. The effects of varying the duration of drug treatment were also examined. 3. In randomly growing cultures nifedipine, like other dihydropyridines concentration-dependently inhibited cell proliferation; the rank order of effect (measured at a concentration of 10 microM) was nifedipine > nisoldipine > nitrendipine approximately nimodipine. 4. In G0/G1 arrested cell cultures, nifedipine concentration-dependently inhibited serum-induced [3H]-thymidine incorporation. In this respect it had similar effects in cell cultures from WKY and SHR. In both SHR and WKY cultures, nifedipine delaye...Continue Reading