Salt sensitive modulation of the interaction between efferent and afferent renal nerve activity mediated by PGE2 and endothelin (ET)

Abstract

Increases in efferent renal sympathetic nerve activity (ERSNA) increase afferent renal nerve activity (ARNA) which in turn decreases ERSNA via activation of the renorenal reflexes in the overall goal of maintaining low ERSNA to limit sodium retention. We examined if dietary sodium modulates the interaction between ERSNA and ARNA and the norepinephrine (NE)‐induced activation of renal sensory nerves. Thermal cutaneous stimulation (HOT) to increase ERSNA was produced by placing the rat's tail in 47 and 49°C water in rats fed high sodium (HNa) and low sodium (LNa) diet (lower heat activation threshold in HNa vs LNa rats). HOT increased ERSNA and ARNA 100120 ± 1830 and 7660±1380 % sec (AUC) in HNa rats and 4370 ± 1290 and 970 ± 420% sec in LNa rats. In isolated renal pelvises from HNa rats, NE 10 pM increased the release of substance P from 7 ± 1 to 12 ± 2 pg/min and PGE2 from 67 ± 1 to 150 ± 13 pg/min. In pelvises from LNa rats, NE 10‐6250 pM had no effect. Renal pelvic administration of the ET B receptor (ETB‐R) antagonist BQ788 blocked the ARNA response to HOT by 76 ± 6% in vivo and the NE‐induced increases in substance P and PGE2 by 65 ± 16 and 34 ± 15% in vitro. Conversely in LNa rats, the ETA‐R antagonist BQ123 enhanced the ARNA response to HOT from 970 to 7360 ± 2124 % sec and the renal pelvic release of substance P produced by NE 6250 pM. NE increased substance P release from 5 ± 0 to 7 ± 1 pg/min (NS) before and from 5 ± 1 to 9 ± 1 pg/min (P<0.01) during BQ123. BQ123 had no effect on the NE‐induced release of PGE2. BQ788 and BQ123 have no effect in normal sodium diet rats.Conclusion: Activation of ETB‐R contributes to the increased PGE2 synthesis and increased interaction between ERSNA and ARNA in HNa rats. Activation of ETA‐R contributes to the decreased interaction between ERSNA and ARNA in LNa rats by a mechanism distal to PGE2 synthesis.