The studies will be performed during two 6-months periods: 1/1-30/6 1998 and 11/98-5/99. Obstruction to urine flow increases renal pelvic pressure (RPP). RPP increases afferent renal nerve activity (ARNA), decreases contralateral efferent renal nerve activity (ERNA) and increases contralateral urinary sodium excretion; a renorenal reflex response. RPP increases the release of PGE2 and substance P (SP). SP activates SP receptors with an increase in ARNA. The renorenal reflexes are impaired in spontaneously hypertensive rats (SHR). Impaired renorenal reflexes would lead to enhanced renal ERNA with sodium retention, factors known to contribute to hypertension. The impaired ARNA response to UP is associated with reduced SP release and impaired activation of renal pelvic SP receptors. In the present study, SP containing neurons and SP receptors will be localized in the renal pelvis of normotensive and hypertensive rats to determine whether the impaired renorenal reflexes in SHR are related to decreased density of SP containing, neurons or SP receptors in the renal pelvis.
In SPECIFIC AIMS number 1-number 3, localization and quantification of SP containing neurons and SP receptors in an isolated rat renal pelvic wall preparation and dorsal root ganglia will be performed by immunohistochemistry and in situ hybridization.
| Kopp, U C; Cicha, M Z; Smith, L A et al. (2001) Nitric oxide modulates renal sensory nerve fibers by mechanisms related to substance P receptor activation. Am J Physiol Regul Integr Comp Physiol 281:R279-90 |
