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.

The purpose of the present study was to obtain evidence for the functional role of presynaptic alpha adrenergic receptors in the intact animal. This aim was approached by investigating the effects 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. Intraperitoneal 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 hr. 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. However, transmural stimulation of the isolated salivary gland for 30 min in the presence of yohimbine caused about 50% reduction in norepinephrine content.(ABSTRACT TRUNCATED AT 250 WORDS)