Comparison of the Effects of the Vasoconstrictive Dihydropyridines BAY K 8644 and CGP 28392 on Isolated Rat Aorta: Different Sensitivities to Ultraviolet Radiation

The effect of BAY K 8644 was compared to that of CGP 28392 in isolated rat thoracic aorta. In low concentration both dihydropyridines had a direct concentration dependent contractile effect that could be eliminated in Ca-free medium and by the Ca-antagonist nifedipine. Readdition of Ca to the Ca-fre...

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Veröffentlicht in:Journal of cardiovascular pharmacology 1986-05, Vol.8 (3), p.476-482
Hauptverfasser: Mikkelsen, Erich O, Nyborg, Niels C. B
Format: Artikel
Sprache:eng
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Zusammenfassung:The effect of BAY K 8644 was compared to that of CGP 28392 in isolated rat thoracic aorta. In low concentration both dihydropyridines had a direct concentration dependent contractile effect that could be eliminated in Ca-free medium and by the Ca-antagonist nifedipine. Readdition of Ca to the Ca-free medium restored the contractile response to both agents. In high concentrations (≥ 10M), both agents depressed active tone. In physiological salt solution containing 15.8 mM, potassium BAY K 8644 was far more potent in contracting rat aorta than CGP 28392. The responses to BAY K 8644 and CGP 28392 were not affected by α- and β-adrenoceptorblockade. Both compounds shifted the noradrenaline- and potassium-concentration response curve to the left and increased the maximal response. Ultraviolet radiation (UVR) had a reversible and marked effect on BAY K 8644 and no effect on CGP 28392 contractions. The UVR-mediated relaxation of BAY K 8644-induced contractions could partly be eliminated by raising extracellular Ca. The results showed that differences according to potency and mode of action exist between BAY K 8644 and CGP 28392 in rat aorta. To explain the effect of UVR on BAY K 8644-induced contractions, a modification of a Ca channel model is proposed that implies the existence of photosensitive proteins located to Ca antagonist binding sites. According to this hypothesis, UVR may induce a reversible binding of BAY K 8644 to “Ca antagonist receptors.”
ISSN:0160-2446
1533-4023
DOI:10.1097/00005344-198605000-00006