Impaired substance P release from renal sensory nerves in SHR involves a pertussis toxin-sensitive mechanism.

نویسندگان

  • Ulla C Kopp
  • Michael Z Cicha
چکیده

Stretching the renal pelvic wall activates renal mechanosensory nerves by a PGE2-mediated release of substance P via activation of the cAMP-PKA pathway. Renal pelvic ANG II modulates the responsiveness of renal sensory nerves by suppressing the PGE2-mediated activation of adenylyl cyclase via a pertussis toxin (PTX)-sensitive mechanism. In SHR, activation of renal mechanosensory nerves is impaired. This is due to suppressed release of substance P in response to increased pelvic pressure. The present study was performed to investigate whether the PGE2-mediated release of substance P was suppressed in SHR vs. WKY and, if so, whether the impaired PGE2-mediated release of substance P was due to ANG II activating a PTX-sensitive mechanism. In an isolated renal pelvic wall preparation, PGE2, 0.14 microM, increased substance P release from 9 +/- 3 to 22 +/- 3 pg/min (P < 0.01) in Wistar-Kyoto rats (WKY), but had no effect in spontaneously hypertensive rats (SHR). A tenfold higher concentration of PGE2, 1.4 microM, was required to increase substance P release in SHR, from 7 +/- 1 to 22 +/- 3 pg/min (P < 0.01). In SHR, treating renal pelvises with losartan enhanced the release of substance P produced by subthreshold concentration of PGE2, 0.3 microM, from 16 +/- 2 to 26 +/- 3 pg/min (P < 0.01). Likewise, treating renal pelvises with PTX enhanced the PGE2-mediated release of substance P from 10 +/- 1 to 33 +/- 3 pg/min (P < 0.01) in SHR. In WKY, neither losartan nor PTX had an effect on the release of substance P produced by subthreshold concentrations of PGE2, 0.03 microM. In conclusion, the impaired responsiveness of renal sensory nerves in SHR involves endogenous ANG II suppressing the PGE2-mediated release of substance P via a PTX-sensitive mechanism.

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R-00493-2003.R1 Impaired substance P release from renal sensory nerves in SHR involves a pertussis toxin sensitive mechanism

Stretching the renal pelvic wall activates renal mechanosensory nerves by a PGE 2-mediated release of substance P via activation of the cAMP-PKA pathway. Renal pelvic angiotensin (ANG) II modulates the responsiveness of renal sensory nerves by suppressing the PGE 2-mediated activation of adenylyl cyclase via a PTX-sensitive mechanism. In SHR, activation of renal mechanosensory nerves is impaire...

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عنوان ژورنال:
  • American journal of physiology. Regulatory, integrative and comparative physiology

دوره 286 2  شماره 

صفحات  -

تاریخ انتشار 2004