Inhibitory renorenal reflexes: a role for substance P or other capsaicin-sensitive neurons

In anesthetized rats, we examined whether inhibitory renorenal reflex responses to renal pelvic mechanoreceptor (MR) and chemoreceptor (CR) stimulation were mediated by substance P (SP)-containing neurons. Capsaicin (0.5 ng to 5 micrograms) injected into the renal pelvis increased afferent renal nerve activity (ARNA) dose dependently, from 60 +/- 19 to 333 +/- 105%. For a given ARNA response, a 100-fold higher dose was required when capsaicin was injected into the renal interstitium compared with the renal pelvis. Renal pelvic administration of SP (25 ng) increased ipsilateral ARNA by 126 +/- 34% and contralateral urine flow rate and urinary sodium excretion by 21 +/- 4 and 28 +/- 7%, respectively, a response similar to that produced by renal MR and CR stimulation. Mean arterial pressure was unaffected. Ipsilateral renal denervation abolished the contralateral diuresis and natriuresis produced by SP. In rats treated with capsaicin (950 mg/kg subcutaneously over 1 wk) to deplete sensory neurons of SP, renal MR and CR stimulation failed to elicit a renorenal reflex response. The data suggest that the renorenal reflex responses to renal MR and CR stimulation are mediated at least, in part, by SP neurons or other sensory neurons susceptible to depletion by capsaicin.