Abstract 81: Hypo-Osmolality Pressor Stimulus is Linked to Transient Receptor Potential Vanilloid 4 (TRPV4) in the Portal Region
Patients with baroreflex impairment have a robust and sustained increase in blood pressure (BP) after water consumption. Using a sino-aortic denervated mouse model (SAD), we identified hypo-osmolality as the stimulus for this osmopressor response (OPR). However, the afferent mechanism of how changes in osmolality are relayed from the gut area to the central nervous system is still unknown. We tested the hypothesis that decreased osmolality is sensed in the portal area after water consumption and that TRPV4 channels in this region are essential for the response. We infused 0.45% or 0.9% saline directly into the portal vein of SAD wild type (WT) and TRPV4-/- mice. An immediate pressor response occurred in WT mice after 0.45% saline but not after 0.9% saline infusion (0.45%: 16 ± 6 vs. 0.9%: -6 ± 2 mmHg, p=0.03). On the other hand, infusion of 0.45% saline into TRPV4-/- mice failed to stimulate a pressor response (-5 ±2 mmHg, p=0.03 for comparison with WT). There are two known nerves that convey afferent signals from the gut to the brain: the vagal and splanchnic nerves. We explored the possible contribution of the splanchnic nerve to OPR by using celiac ganglionectomized (CGX) and sham WT mice. Both CGX and sham mice had a robust increase in BP after water infusion into the duodenum (CGX: 10 ± 2 vs. SHAM: 12 ± 1 mmHg, p=0.5). However, the response was shortened by ganglionectomy. Ten minutes after water, BP had returned to normal in CGX, while it remaining elevated in sham mice (ΔMAP for CGX: 0.3 ± 2 vs. 9 ± 1.7 mmHg, p=0.01). In mice that underwent both CGX and vagotomy, we observed full OPR (ΔMAP for CGX+Vagotomy: 17 ± 6mmHg vs. Sham: 30 ± 8mmHg, p=0.26). Therefore, we conclude that TRPV4 channels in the portal region are essential for the OPR, and the celiac ganglia play an important role in maintaining BP elevation, while the vagus nerve is unlikely to contribute to the water response.
- © 2013 by American Heart Association, Inc.