PERFUSION WITH CALCIUM FREE SOLUTION POTENTIATES PRAZOSIN BLOCKADE OF NORADRENALINE INDUCED PRESSOR RESPONSES IN THE MESENTERIC BED OF THE RAT

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Abstract
Dose response curves have been constructed from pressor responses to bolus injections of noradrenaline (NA) in the perfused mesenteric bed of the rat. Prazosin (1.0-50 nM) caused a shift to the right of these dose response curves and significantly depressed the maximum obtainable response without any significant change in slope, whereas corynanthine exhibited classical competitive antagonism. When perfused with calcium-free solution, the pressor responses to NA were of shorter duration and the maximum obtainable response was reduced by 26.9 .+-. 3.1%. When perfused with calcium-free solution the antagonistic effect of corynanthine was unchanged but that of prazosin was enhanced such that 5.0nM of prazosin now caused a much greater depression of the maximum NA-induced pressor responses and a marked reduction in slope of the dose response curve. Corynanthine (10 .mu.M) was able to reverse these antagonist effects of prazosin. These observations are consistent with the suggestion that prazosin selectively antagonizes NA-induced calcium release.