Effects of chronic norepinephrine administration on sympathetic neurotransmission in the isolated perfused rat kidney.

The effects of chronic NE administration (100 micrograms/kg/hr s.c., 6 days) on the stimulus-induced overflow of neurotransmitter from the isolated perfused rat kidney were examined. This treatment increased renal NE content and increased the absolute stimulus-induced overflow of NE. The increase in absolute overflow was not simply the result of the increase in renal NE content as fractional overflow was also increased slightly (20%). Alpha adrenoceptor blockade with phentolamine eliminated the NE treatment-induced difference in fractional overflow. However, the dose-response curves to phentolamine and the alpha-2 adrenoceptor agonist UK 14,304 on stimulus-induced overflow from the kidney were not significantly different after NE treatment. Chronic EPI treatment (same dose) produced an 80% increase in fractional stimulus-induced overflow of neurotransmitter but the dose-response curve to UK 14,304 was shifted only slight to the right (3-fold) of the control curve. No influence of prejunctional beta adrenoceptors on stimulus-induced overflow was observed in either the control of the NE-treated group. In conclusion, the data regarding fractional overflow and the effects of the phentolamine suggest that NE treatment produces minimal change whereas EPI treatment produces marked decreases in the influence in prejunctional alpha adrenoceptors. However, although the data with UK 14,304 after NE treatment support this conclusion, the failure of EPI treatment to alter the dose-response curve to UK 14,304 does not. The apparent contradiction of the results with the alpha adrenoceptor agonist in the EPI-treated group as well as the large differences between the effects of NE vs. EPI treatment on stimulus-induced overflow and prejunctional alpha adrenoceptor function cannot be explained at this time.