Direct Role of Endothelin B Receptors on Renal Afferent Nerves on Blood Pressure Control

Hypertension is prevalent, dangerous, and can lead to cardiovascular disease. Although mechanisms causing hypertension are incompletely understood, the autonomic nervous system plays a role. Endothelin B Receptors (ET B R) regulate sodium excretion, and we theorize they regulate blood pressure through renal afferent nerve signaling. Prior research demonstrates that dysfunction of ET B R increases blood pressure sensitivity, however the direct role of ET B R on renal afferent nerves is not known. We hypothesize that direct renal afferent nerve ET B R antagonism increases blood pressure in rats on a high salt diet. Male and female Sprague-Dawley rats were implanted with telemetry devices to record blood pressure, and a catheter placed under the kidney capsule delivered vehicle via osmotic minipumps for baseline (BL). Pumps were changed to ET B R antagonist (A192621+NS, 100 µg/d). Normal salt (NS, 0.49% NaCl) diet was fed during baseline and 7 days of A192621, animals were then fed a high salt diet (A192621+HS, 4.0% NaCl) for 7 days. Control group did not have a renal catheter and received drug systematically. Urine was collected during the last two days of each period. Endothelin urinary excretion was similar between control and A192621+HS (74.2±7.8 vs 69.6±8.3 pg/day, p=0.7027). Systolic blood pressure was similar between control and A192621+HS (132.1±3.0 vs. 135.2±5.8 mmHg, p=0.6605). Heart rate was similar between control and A192621+HS (359.9±11.5 vs. 362.6±16.3 bpm, p=0.8968). Kidney cortex NE concentration was analyzed through ELISA and discovered that the treated kidney’s NE concentration was significantly higher than the contralateral kidney (0.2835±0.0603 vs. 0.1861±0.0497 ng/µg, p=.0.0037). This study indicates that renal afferent nerve ET B R may not be involved in blood pressure control during high salt diets. The cortex NE data indicates that surgery proved successful, and that treatment did have a positive effect on local sympathetic signaling. The results proved inconclusive and future work with revised study design and approach is needed. This project is funded by National Health Institute (NIH) grants K01HL159047 to Dr. Bryan K. Becker This abstract was presented at the American Physiology Summit 2025 and is only available in HTML format. There is no downloadable file or PDF version. The Physiology editorial board was not involved in the peer review process.