Enhanced endogenous neurotransmitter overflow in the isolated perfused rat kidney after chronic epinephrine administration: lack of a prejunctional beta adrenoceptor influence.

This study examines stimulus-induced overflow of endogenous catecholamines from the isolated perfused kidney of rats after epinephrine (EPI) administration at 100 micrograms/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 co-release 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 microM 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 microM 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-induced overflow unless the dominant inhibitory alpha adrenoceptor mechanism is inactivated.(ABSTRACT TRUNCATED AT 250 WORDS)

• Publication year

  1988

• Venue

  Journal of Pharmacology and Experimental Therapeutics

• Publication date

  1988-01-01

• Fields of study

  Medicine, Chemistry

• Identifiers
  DOI 10.1016/s0022-3565(25)24241-0PMID 2891841
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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