Nifedipine and Bay K 8644 Induce an Increase of [Ca2+] i and Nitric Oxide in Endothelial Cells

Abstract

Background: The dihydropyridine-induced vasorelaxation is partly dependent on the endothelium, which does not express L-type calcium channels. Because nitric oxide (NO) is one of the most important endothelium-derived vasorelaxing factors, we investigated how the calcium antagonist nifedipine and the calcium agonist Bay K 8644 modulate intracellu lar calcium and NO formation in porcine endothelial cells.

Methods and Results: NO formation of porcine aortic endothelial cell cultures and of native endothelium of intact porcine coronary arteries was measured with an electrochemi cal electrode, and the intracellular concentration of Ca²⁺ [Ca²⁺]_i was evaluated using the Fura-2 technique. Nifedipine induced a concentration-dependent [0.01-1 μmol/L] increase in [Ca²⁺]_i and NO formation in cultured porcine aortic endothelial cells, and moreover a dose- dependent NO formation in native endothelial cells from intact porcine coronary arteries, which was higher than in cultured cells. This effect was inhibited by N-nitro-L-arginine, a spe cific NO synthase inhibitor. Bay K 8644 caused a [Ca²⁺]_i increase and NO release in cul tured cells, too, although to a lesser extent. Nifedipine-induced and Bay K 8644-induced [Ca²⁺]_i rise could be blocked by removal of extracellular calcium, indicating that a calcium influx may be involved.

Conclusions: The calcium antagonist nifedipine as well as the calcium agonist Bay K 8644 cause an increase of [Ca²⁺]_i and NO in porcine endothelium. Therefore, these effects seem to be related to the dihydropyridines as a substance class, which may explain the endothe lial component in dihydropyridine-induced vasorelaxation.