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Pharmacologicalreactivity of humanepicardial coronaryarteries: phasic andtonic responses tovasoconstrictoragents differentiatedby nifedipine A StorkThomas M. Cocks1994 год

Pharmacological reactivity of human epicardial coronary arteries: phasic and tonic responses to vasoconstrictor agents differentiated by nifedipine
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Аннотация: Human epicardial coronary artery rings, freshly obtained from cardiac transplantation patients, commonly exhibited phasic contractile activity in vitro . This activity occurred either spontaneously or in response to vasoconstrictor stimulation. Nifedipine pretreatment (1 n m ‐0.1 μ m ) reduced both types of phasic contractions in a concentration‐dependent manner. At 0.1 μ m nifedipine, spontaneous contractions were completely abolished, as were phasic contractions induced by U46619, endothelin‐1 or 5‐hydroxytryptamine (5‐HT). For U46619 (0.1–100 n m ), the largest phasic contractions (amplitude peak to trough) occurred over the mid‐range of concentrations used (1–10 n m ). At higher concentrations (30–100 n m ), phasic activity was reduced as the response reached a maximum. Estimated pEC 50 values for the upper phasic and lower phasic curves were significantly different (8.71 ± 0.13 versus 7.90 ± 0.11; P < 0.05; n = 10). In the presence of nifedipine (0.1 μ m ), the purely tonic contraction curve to U46619 was similar to the lower phasic curve in the absence of nifedipine (pEC 50 = 8.14 ± 0.06, n = 10). Similar results were obtained for endothelin‐1 (0.1 −100 n m ). Responses to 5‐HT (1 n m ‐3 μ m ) were more variable. The largest phasic contractions were spread unevenly throughout the concentration‐response curve. In the presence of nifedipine (0.1 μ m ), the curve to 5‐HT was significantly depressed in range but not sensitivity (pEC 50 ) when compared with the phasic curves. In conclusion, activation of dihydropyridine‐sensitive voltage‐operated Ca 2+ channels mediated the phasic contractions commonly observed in human epicardial coronary arteries. These contractions amplified the contractile responses to low concentrations of vasoconstrictors. Inhibition of phasic activity by the Ca 2+ channel antagonist, nifedipine, allowed the tonic vasoconstrictor profile of human isolated coronary artery to be determined which is important information for the accurate quantitative assessment of vasodilator responses in this tissue in vitro .
Год издания: 1994
Авторы: A Stork, Thomas M. Cocks
Издательство: Wiley
Источник: British Journal of Pharmacology
Ключевые слова: Cardiac electrophysiology and arrhythmias, Cardiac Arrhythmias and Treatments, Nitric Oxide and Endothelin Effects
Другие ссылки: British Journal of Pharmacology (HTML)
Europe PMC (PubMed Central) (PDF)
Europe PMC (PubMed Central) (HTML)
PubMed Central (HTML)
PubMed (HTML)