Enhanced endogenous neurotransmitter overflow in the isolated perfused rat kidney after chronic epinephrine administration: lack of a prejunctional beta adrenoceptor influence
Schwartz, D.D.; Eikenburg, D.C.
Journal of Pharmacology and Experimental Therapeutics 244(1): 11-18
1988
ISSN/ISBN: 0022-3565 PMID: 2891841 Document Number: 314602
This study examines stimulus-induced overflow of endogenous catecholamines from the isolated perfused kidney of rats after epinephrine (EPI) administration at 100 .mu.g/kg/hr for 6 days via s.c. implanted osmotic minipumps. This regimen resulted in the incorporation of EPI into renal catecholamine stores and the corelease of EPI with norepinephrine during periarterial nerve stimulation. Stimulus-induced (1 Hz) absolute and fractional overflows of neurotransmitter were significantly greater in the EPI-treated rats. These differences in overflow were not altered by uptake blockade. Alpha adrenoceptor blockade with phentolamine (10-9-10-5) alone increased overflow in a dose-dependent manner in both groups, although to a greater extent in the EPI-treated group. However, in the presence of 1 .mu.M propranolol the effect of phentolamine in the EPI-treated group was greatly reduced such that, in the presence of propranolol, phentolamine was less effective in the EPI-treated vs. vehicle-treated rats. Beta adrenoceptor blockade alone with propranolol (10-9-10-6 M) did not alter stimulus-induced overflow in either group but propranolol dose dependently reduced fractional overflow in the EPI-treated rats when the experiments were done in the presence of 10 .mu.M phentolamine. It is concluded that the enhanced fractional overflow observed in the kidneys of EPI-treated rats was not due to beta adrenoceptor activation, but rather, a reduced influence of the prejunctional alpha adrenoceptor-mediated negative feedback loop. Beta adrenoceptor activation by neurally released EPI does not appear to modulate stimulus-iduced overflow unless the dominant inhibitory alpha adenoceptor mechanism is inactivated. Therefore, this study does not provide evidence that chronic elevation of plasma EPI concentrations produces facilitation of sympathetic neurotransmitter release in the kidney via prejunctional beta adrenoceptor activation.