AJP - Regulatory, Integrative and Comparative Physiology, Vol 264, Issue 3 647-R653, Copyright © 1993 by American Physiological Society
Effects of the substance P receptor antagonist CP-96,345 on renal sensory receptor activation
U. C. Kopp and L. A. Smith
Department of Internal Medicine, University of Iowa College of Medicine, Iowa City.
In anesthetized rats, we examined the effects of the substance P (SP)
receptor antagonist CP-96,345 on the renorenal reflex responses to renal
mechanoreceptor (MR) stimulation produced by increased ureteral pressure.
Renal pelvic administration of SP at 0.16, 0.8, 4.0, 20, and 100
micrograms/ml increased ipsilateral afferent renal nerve activity (ARNA) in
a concentration-dependent fashion, 45 +/- 28, 134 +/- 26, 185 +/- 24, 185
+/- 25, and 274 +/- 39%, respectively. Renal pelvic perfusion with
CP-96,345 at 0.01, 0.1, and 1.0 mg/ml dose-dependently reduced the ARNA
response to 4.0 micrograms/ml SP, by 5 +/- 17, 46 +/- 9, and 72 +/- 12%,
respectively. Increasing ureteral pressure three times in the presence of
renal pelvic perfusion with vehicle, 1 mg/ml CP-96,345, and vehicle,
increased ARNA 77 +/- 21, 29 +/- 13, and 101 +/- 36%, respectively. Thus
CP-96,345 produced a reversible blockade of the ARNA responses to renal MR
stimulation. Increasing ureteral pressure three times in the presence of
renal pelvic perfusion with vehicle, CP-96,345 (1 mg/ml), and CP-96,345 +
25-40 micrograms/ml SP, increased ARNA 108 +/- 15, 43 +/- 14, and 153 +/-
63%, respectively. Thus CP-96,345 produced a competitive blockade of the
ARNA responses to renal MR stimulation. The contralateral diuretic and
natriuretic responses to increased ureteral pressure were also blocked in a
reversible and competitive fashion by CP-96,345. The inactive 2R,3R
enantiomer of CP-96,345, CP-96,344 (1 mg/ml). had no effect on the
ipsilateral ARNA or the contralateral renal excretory responses to
increased ureteral pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
