Sympathetic nerve stimulation on the perfused rat heart

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Abstract
Summary Rat isolated hearts with the sympathetic nerves attached were perfused with (-)-3H-noradrenaline in order to label the storage vesicles of the adrenergic nerves. Release was induced either by electrical stimulation of the nerves (3 Hz, 1 min) or by perfusion with high K+ solution (54 mM). The overflow of 3H-noradrenaline and its metabolites was determined by liquid scintillation counting after separation of the compounds by column chromatography. The experimental conditions ensured a minor contribution of 3H-metabolites to the evoked total tritium overflow. The release of 3H-noradrenaline evoked by nerve stimulation or high K+ solution was decreased in the presence of the muscarinic agonist, methacholine. N-methylatropine reversed the inhibition completely. Thus, the rat heart contains inhibitory muscarine receptors modulating noradrenaline release from adrenergic nerve fibres. In order to compare the presynaptic muscarine receptors with postsynaptic muscarine receptors in one and the same organ, the pA2 values of N-methylatropine and pirenzepine at both of these sites were measured. The antagonism of methacholine-induced inhibition of 3H-noradrenaline over-flow was determined as the presynaptic parameter. pA2 values of 9.61 for N-methylatropine and 6.63 for pirenzepine were found. The methacholine-induced inhibition of the atrial tension development of isolated left rat atria paced at 2 Hz was measured as a postsynaptic parameter. pA2 values of 9.90 for N-methylatropine and 6.69 for pirenzepine were found. The postsynaptic pA2 values did not differ from the presynaptic affinity constants indicating that neither substance revealed differences in structure between neuronal and myocardial muscarine receptors in the rat heart.