In normotensive rats, increased renal pelvic pressure stimulates the r
elease of prostaglandin E and substance P, which in turn leads to an i
ncrease in afferent renal nerve activity (ARNA) and a contralateral na
triuresis, a contralateral inhibitory renorenal reflex. In spontaneous
ly hypertensive rats (SHR), increasing renal pelvic pressure failed to
increase afferent renal nerve activity. The inhibitory nature of reno
renal reflexes indicates that impaired renorenal reflexes could contri
bute to increased sodium retention in SHR. Phorbol esters, known to ac
tivate protein kinase C, increase afferent renal nerve activity in Wis
tar-Kyoto rats (WKY) but not in SHR. We examined the mechanisms involv
ed in the impaired responses to renal sensory receptor activation in S
HR. The phorbol ester 4 beta-phorbol 12,13-dibutyrate increased renal
pelvic protein kinase C activity similarly in SHR and WKY. Increasing
renal pelvic pressure increased afferent renal nerve activity in WKY (
27 +/- 2%) but not in SHR. Renal pelvic release of prostaglandin E inc
reased similarly in WKY and SHR, from 0.8 +/- 0.1 to 2.0 +/- 0.4 ng/mi
n and 0.7 +/- 0.1 to 1.4 +/- 0.2 ng/min. Renal pelvic release of subst
ance P was greater (P < .01) in WKY, from 16.3 +/- 3.8 to 41.8 +/- 7.4
pg/min, than in SHR, from 9.9 +/- 1.7 to 17.0 +/- 3.2 pg/min. In WKY,
renal pelvic administration of substance P at 0.8, 4, and 20 mu g/mL
increased ARNA 382 +/- 69, 750 +/- 233, and 783 +/- 124% second (area
under the curve of afferent renal nerve activity versus time). In SHR,
substance P at 0.8 to 20 mu g/mL failed to increase ARNA. These findi
ngs demonstrate that the impaired afferent renal nerve activity respon
se to increased renal pelvic pressure is related to decreased release
of substance P and/or impaired activation of substance P receptors.