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- W119131034 abstract "Stimulation of ETB receptors (ETB-R) contributes to the natriuretic renorenal reflexes elicited by NE-mediated activation of the renal sensory nerves. We now examined the mechanisms involved in the ETB-R mediated activation of these nerves. Renal pelvic administration of the ETB-R agonist IRL1620 increased ARNA 3800±850 %·sec which was blocked by the ETB-R antagonist BQ788 or indomethacin. Adding IRL1620 to an isolated renal pelvic preparation resulted in increases in the release of PGE2 from 114±18 to 414±64 pg/min and substance P from 7.8±1.0 to 16.6±1.6 pg/min that were also blocked by BQ788 or indomethacin. The concentration of IRL1620 used was 20 μM in vitro vs 10 nM in vivo suggesting reduced responsiveness of ETB-R in the denervated in vitro preparation. 2 pM NE + 25 nM IRL1620 increased renal pelvic release of PGE2 from 90±9 to 240±30 pg/min and substance P from 5.3±0.3 to 12.4±0.8 pg/min. No effect was produced by 2 pM NE or 25 nM IRL1620 alone. Renal pelvic administration of prazosin reduced the ARNA responses to IRL1620 by 81±13% in vivo. Thus NE facilitates the responsiveness of ETB-R. The intracellular mechanisms contributing to the ETB-R activation of renal sensory nerves were examined by renal pelvic administration of the PLC inhibitor U73122 and PKC inhibitor GF109203X (GFX). U73122 and GFX reduced the ARNA responses to IRL1620 by 48±16% and 100±0% in vivo. Likewise, U73122 and GFX reduced the increases in substance P release produced by 2 pM NE+25 nM IRL1620 by 38±5% by and 46±5% in vitro. The NE+IRL1620 induced increases in PGE2 release was reduced by 48±11% by GFX. Conclusion: There is a reciprocal interaction between α1-adrenoceptors and ETB-R in the activation of renal sensory nerves. Activation of the PLC/PKC pathway contributes to the ETB-R induced increases in renal pelvic release of PGE2 and substance P and ARNA." @default.
- W119131034 created "2016-06-24" @default.
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- W119131034 date "2010-04-01" @default.
- W119131034 modified "2023-10-05" @default.
- W119131034 title "Interaction Between Endothelin (ET) and Norepinephrine (NE) in the Activation of Renal Sensory Nerves" @default.
- W119131034 doi "https://doi.org/10.1096/fasebj.24.1_supplement.794.2" @default.
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