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

Institut fuer Pharmakologie, Cologne, Germany

Andreas Mueller

Institut fuer Pharmakologie, Cologne, Germany

Renate Roesen

Institut fuer Pharmakologie, Cologne, Germany

Wolfgang Klaus

Institut fuer Pharmakologie, Cologne, Germany

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.

Key Words: calcium channel antagonists • calcium channel agonists • dihydropyridines • nitric oxide release.

Journal of Cardiovascular Pharmacology and Therapeutics, Vol. 4, No. 3, 175-181 (1999)
DOI: 10.1177/107424849900400307


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