REDUCTION IN NOREPINEPHRINE CONTENT OF SYMPATHETIC NEUROEFFECTOR ORGANS BY ALPHA-ADRENERGIC ANTAGONISTS AND NERVE-STIMULATION - EVIDENCE FOR PRESYNAPTIC CONTROL OF SYMPATHETIC TRANSMITTER RELEASE IN INTACT ANIMAL

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  • 1 January 1984
    • journal article
    • research article
    • Vol. 228  (2) , 287-292
Abstract
Evidence for the functional role of presynaptic .alpha. adrenergic receptors in the intact animal was obtained. The effecs of .alpha. adrenergic blocking agents and other hypotensive agents on the norepinephrine content of the heart, spleen and the salivary gland of the normal and adrenalectomized rats were studied. I.p. administration of saline, hydralazine (10 mg/kg), yohimbine (1 mg/kg), prazosin (0.5 mg/kg) or bretylium (10 mg/kg) to normal or adrenalectomized rats had no significant effect on norepinephrine content of these organs over 4 h. A combined treatment of hydralazine plus yohimbine produced 50 and 27% reduction in norepinephrine content of the heart and spleen, respectively. The effect of hydralazine plus yohimbine was more pronounced in adrenalectomized rats (62% for the heart and 50% for the spleen). Administration of phentolamine (2 mg/kg) alone resulted in about 40% reduction in norepinephrine content of the normal rat hearts. A combination of hydralazine plus phentolamine enhanced the degree of norepinephrine depletion in the hearts (52%) and also produced a small loss (17%) in the spleen. The depleting effects of various drugs were completely prevented by prior treatment of rats with bretylium. Norepinephrine content of the salivary gland remained unchanged in all of the above-treated rats. Transmural stimulation of the isolated salivary gland for 30 min in the presence of yohimbine caused about 50% reduction in norepinephrine content. Hypotensive agents (hydralazine, prazosin, etc.) may reflexly enhance the sympathetic drive to the heart, but this action alone is not sufficient to produce reduction in norepinephrine content. Blockade of presynaptic .alpha. receptors (yohimbine) alone is unable to produce a loss in tissue norepinephrine content. Enhanced sympathetic drive to the heart initiated by hypotensive action plus presynaptic .alpha. receptor blockade (phentolamine, hydralazine plus yohimbine, etc.) is essential to cause a marked facilitation of norepinephrine release which then results in a net loss of the transmitter from their sympathetic nerves. The reflex action would apparently be even more pronounced in adrenalectomized rats and may recruit sympathetic nerves of tissues (i.e., spleen), in addition to the heart, to maintain circulating catecholamiens; blockade of the presynaptic .alpha. receptor is then expected to further lower tissue norepinephrine content. The presynaptic modulation of the sympathetic transmitter apparently occurs in conscious animals.