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

Abstract

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.

CGRP Activates Renal Pelvic Substance P Receptors by Retarding Substance P Metabolism

“…The procedures for stimulating and recording ARNA have been previously described in detail. [1][2][3][4] In short, the left kidney was approached through a flank incision, a PE-10 catheter was placed in the right ureter for collection of urine, and a PE-60 catheter was placed in the left ureter with its tip in the pelvis. A PE-10 catheter was placed inside the PE-60 catheter for administration of vehicle and various experimental drugs into the renal pelvis.…”

“…[2][3][4] We reasoned that if the greater ARNA response to the combined administration of substance P and CGRP ( Figure 1) was related to CGRP increasing the availability of substance P, then CGRP would enhance the ARNA response to increased renal pelvic pressure. The results are shown in Figure 2A.…”

“…Key Words: sensory neurons Ⅲ endopeptidase, neutral Ⅲ afferent renal nerve O bstruction to urine flow increases renal pelvic pressure and activates renal mechanosensitive neurons, resulting in an increase in ipsilateral afferent renal nerve activity (ARNA). [1][2][3][4] The increase in ARNA produces a decrease in contralateral efferent renal nerve activity and a contralateral diuresis and natriuresis, known as the contralateral inhibitory renorenal reflex.The mechanosensitive neurons activated in this reflex are mainly located in the renal pelvic wall. 5,6 Activation of substance P receptors in the renal pelvic area plays an essential role in the activation of renal mechanosensitive neurons.…”

“…[1][2][3][4] The increase in ARNA produces a decrease in contralateral efferent renal nerve activity and a contralateral diuresis and natriuresis, known as the contralateral inhibitory renorenal reflex.…”

“…5,6 Activation of substance P receptors in the renal pelvic area plays an essential role in the activation of renal mechanosensitive neurons. [2][3][4] The renal pelvic sensory neurons contain substance P, and increasing renal pelvic pressure increases renal pelvic release of substance P. 3,4 Similar to sensory neurons in other tissues, the renal sensory neurons also contain calcitonin gene-related peptide (CGRP), with substance P and CGRP being colocalized in many neurons. 5,6 Administration of CGRP into the renal pelvis results in an increase in ARNA that is blocked by a CGRP receptor antagonist, suggesting the presence of CGRP receptors in the renal pelvic area.…”