In isolated human distal radial arteries, nifedipine is the most effective calcium channel antagonist for producing relaxation, and contractions induced by 5-hydroxytryptamine and norepinephrine are critically dependent on extracellular calcium.
A comparison was made between the efficacies and potencies of calcium channel antagonists on contractions induced by 5-hydroxytryptamine, norepinephrine, or high-potassium buffer in isolated human distal radial arteries. Also, the impact of removal of extracellular calcium ions on contractions induced by 5-hydroxytryptamine or norepinephrine was assessed. Isometric contractions were induced by agonists, and relaxant responses to calcium channel antagonists, nifedipine, diltiazem, verapamil, or mibefradil were examined. 5-hydroxytryptamine-induced contractions when compared with norepinephrine or high-potassium induced contractions were significantly more sensitive to inhibition by nifedipine (pIC50 = 7.53 +/- 0.15; 6.78 +/- 0.12; 6.6 +/- 0.22, respectively, mean +/- SEM). Diltiazem was more effective in producing relaxations when contractions were elicited with 5-hydroxytryptamine (pIC50 = 6.48 +/- 0.84) or norepinephrine (pIC50 = 6.20 +/- 0.21) than with high potassium (pIC50 = 5.43 +/- 0.10). Verapamil was more effective at relaxing arteries contracted with 5-hydroxytryptamine (pIC50 = 6.09 +/- 0.19) or norepinephrine (pIC50 = 6.00 +/- 0.17) than with high potassium (pIC50 = 5.60 +/- 0.16). Mibefradil was not very effective in producing relaxations. The studies revealed that removal of extracellular calcium significantly attenuated contractions produced by 5-hydroxytryptamine (-67.7 +/- 6.3%) and norepinephrine (-89 +/- 1.5%). In conclusion, our data indicates that nifedipine was the most effective drug in producing relaxations; also, contractions produced by 5-hydroxytryptamine and norepinephrine were found to be critically dependent on the presence of extracellular calcium.
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Duggan et al. (2003) studied this question.
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