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Effects of ouabain on the nerve stimulation-evoked release of norepinephrine from the isolated perfused guinea-pig heart

RL Panek, RR Gaddis and WR Dixon

The isolated perfused guinea-pig heart prelabeled with (-)-[7-3H]- norepinephrine was used to examine the effects of increasing concentrations of ouabain on the sympathetic nerve stimulation-evoked release of endogenous norepinephrine and [3H]norepinephrine in the presence and absence of physostigmine or atropine. The overflow of norepinephrine and [3H]norepinephrine from guinea-pig hearts was measured during postganglionic stimulation of the cardiac accelerator fibers (5 Hz for 60 sec, 2 msec duration, for 300 pulses). Perfusion with 10(-7) M ouabain for 20 min had no effect on the release of norepinephrine or [3H]norepinephrine after nerve stimulation. However, perfusion with either 10(-6) or 3 X 10(-6) M ouabain for 15 min resulted in a significant decrease in the nerve stimulation-evoked release of norepinephrine (44.6 +/- 2.24 and 44.0 +/- 2.17%, respectively) and [3H]norepinephrine (43.8 +/- 1.62 and 44.9 +/- 2.16%, respectively) compared with previous control outputs. Perfusion of hearts with physostigmine (10(-6) M), an acetylcholinesterase inhibitor, or atropine (3 X 10(-6) M), a muscarinic blocking agent, did not alter the release of norepinephrine or [3H]norepinephrine after nerve stimulation. Perfusion with physostigmine during perfusion with 10(-6) M ouabain resulted in a decrease in the release of norepinephrine and [3H]norepinephrine only slightly greater than 10(-6) M ouabain alone, which was not significant, but the release of norepinephrine during stimulations performed after a 45-min washout of 10(-6) M ouabain was decreased significantly when 10(-6) M physostigmine was present. Perfusion of hearts with atropine during perfusion with either 10(-6) or 3 X 10(-6) M ouabain reversed the inhibitory effect of ouabain on the release of norepinephrine and [3H]norepinephrine.(ABSTRACT TRUNCATED AT 250 WORDS)

Volume 236, Issue 1, pp. 212-218, 01/01/1986
Copyright © 1986 by American Society for Pharmacology and Experimental Therapeutics






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Copyright © 1986 by the American Society for Pharmacology and Experimental Therapeutics.