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-free medium restored the contractile response to both agents. In high concentrations (greater than or equal to 10(-5) M), 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 alpha- and beta-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."
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D000818:Animals; D001013:Aorta, Thoracic; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000037:antagonists & inhibitors / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011188:Potassium / Q000494:pharmacology; D011725:Pyridines / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D051381:Rats; D011921:Rats, Inbred WKY; D014466:Ultraviolet Rays; D014661:Vasoconstriction / Q000187:drug effects*
D002121:Calcium Channel Blockers; D011725:Pyridines; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C040525:CGP 28392; D009543:Nifedipine; D011188:Potassium; D002118:Calcium; D009638:Norepinephrine