Interaction between endothelin and angiotensin in the activation of renal sensory nerves

Abstract

Increasing renal pelvic pressure increases afferent renal nerve activity (ARNA) and urinary sodium excretion. Low sodium (LNA) diet impairs and high Na diet (HNA) enhances the activation of renal sensory nerves. Renal pelvic administration of losartan or the endothelin A receptor (ETA-R) antagonist BQ123 enhances the activation of renal sensory nerves in LNA diet rats. We now examined if angiotensin (ANG) II suppresses ARNA via interaction with ET. ANG II is present in renal pelvis and its levels are higher in LNA than in HNA diet rats. ET-1 is also present in renal pelvis, its levels being similar in LNA and HNA diet, 13∀2 and 13∀2 pg/mg protein. The ET-1 levels in renal pelvis were lower than in papilla but higher than in cortex; 191∀33 and 1.3∀0.1 pg/mg protein. In LNA diet rats, increasing renal pelvic pressure 7.5 mmHg in the presence of renal pelvic perfusion with vehicle, losartan and losartan+BQ123 increased ARNA 7∀2, 14∀2 and 16∀3%. Thus losartan and losartan+BQ123 resulted in similar enhancements of the ARNA response (P<0.01 vs vehicle). Similar results were produced when renal pelvis was perfused with BQ123 before BQ123+losartan. In isolated renal pelvises from LNA diet rats, PGE2 failed to increase substance P (SP) release. Adding losartan or losartan+BQ123 to the incubation bath enhanced the PGE2-mediated SP release to a similar extent, from 7∀1 to 15∀2 and from 9∀1 to 16∀1 pg/min, both P<0.01. Similar results were produced by incubating pelvises in BQ123 or BQ123+losartan. In isolated pelvises from HNA diet rats, PGE2 increased SP, from 5∀2 to 13∀2 pg/min (P<0.01). Adding ANG II to the bath abolished the PGE2-mediated SP release. However, incubating the pelvises with ANG II+BQ123 restored the PGE2-mediated SP release, from 6∀1 to 13∀1 pg/min (P<0.01). Conclusion, ET-1 by activating ETA-R contributes to ANG II-mediated suppression of the activation of renal sensory nerves.