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(Hypertension. 1998;31:815-822.)
© 1998 American Heart Association, Inc.

Scientific Contributions

Renal Substance P–Containing Neurons and Substance P Receptors Impaired in Hypertension

Ulla C. Kopp; Michael Z. Cicha; Donna M. Farley; Lori A. Smith; ; Bradley S. Dixon

From the Departments of Internal Medicine and Obstetrics/Gynecology, University of Iowa College of Medicine, and Department of Veterans Affairs Medical Center, Iowa City, Iowa.

Abstract—In normotensive rats, increased renal pelvic pressure stimulates the release of prostaglandin E and substance P, which in turn leads to an increase in afferent renal nerve activity (ARNA) and a contralateral natriuresis, a contralateral inhibitory renorenal reflex. In spontaneously hypertensive rats (SHR), increasing renal pelvic pressure failed to increase afferent renal nerve activity. The inhibitory nature of renorenal reflexes indicates that impaired renorenal reflexes could contribute to increased sodium retention in SHR. Phorbol esters, known to activate protein kinase C, increase afferent renal nerve activity in Wistar-Kyoto rats (WKY) but not in SHR. We examined the mechanisms involved in the impaired responses to renal sensory receptor activation in SHR. The phorbol ester 4ß-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 increased similarly in WKY and SHR, from 0.8±0.1 to 2.0±0.4 ng/min and 0.7±0.1 to 1.4±0.2 ng/min. Renal pelvic release of substance 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 µg/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 µg/mL failed to increase ARNA. These findings demonstrate that the impaired afferent renal nerve activity response to increased renal pelvic pressure is related to decreased release of substance P and/or impaired activation of substance P receptors.

Key Words: afferent renal nerve activity • receptors, sensory • prostaglandins • protein kinase C • substance P • rats, inbred SHR

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