RENAL SUBSTANCE P-CONTAINING NEURONS AND SUBSTANCE-P RECEPTORS IMPAIRED IN HYPERTENSION

Citation
Uc. Kopp et al., RENAL SUBSTANCE P-CONTAINING NEURONS AND SUBSTANCE-P RECEPTORS IMPAIRED IN HYPERTENSION, Hypertension, 31(3), 1998, pp. 815-822
Citations number
52
Categorie Soggetti
Peripheal Vascular Diseas
Journal title
ISSN journal
0194911X
Volume
31
Issue
3
Year of publication
1998
Pages
815 - 822
Database
ISI
SICI code
0194-911X(1998)31:3<815:RSPNAS>2.0.ZU;2-W
Abstract
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.