The venous circulation is often “forgotten,” as cardiovascular research and therapeutic intervention focusses predominantly on arteries. However, systemic veins store two-thirds of blood volume at rest, with reservoir beds such as the mesenteric circulation receiving dense sympathetic innervation, suggesting a critical neurogenic role for the mobilization of blood. The impact of hypertension on sympathetic regulation of venous circulation remains unclear. We hypothesized that capacity of mesenteric vasculature is impaired in spontaneously hypertensive rats (SHR) and that reducing sympathetic drive will increase mesenteric buffering of excess volume.SHR (n=6) and Wistar rats (n=7) were instrumented with telemeters recording arterial and venous pressures, and an atrial balloon for assessment of mean circulatory filling pressure (MCFP). Arterial (inflow) and venous (outflow) mesenteric flow probes were implanted to measure total mesenteric volume fluctuation. Mesenteric vascular capacity was challenged with 20% volume load of intravenous saline. In SHR sympathetic drive was reduced via hexamethonium (10mg/kg) or via carotid body denervation (CBD).MCFP was elevated in SHR (+2.7±0.5mmHg, p<0.01 vs Wistars). MCFP in SHR was reduced by hexamethonium (-2.6±0.6; p=0.01 vs Baseline, n=5) and CBD (‑2.0±0.7mmHg; p=0.04 vs Baseline, n=5). In normotensives volume load was accommodated by the mesenteric bed, with a net total influx of blood (+5.4±2.2ml; n=7). In contrast, SHR showed a counter-intuitive net efflux of blood from the mesenteric bed (-1.6±1.4ml; p=0.04 vs Wistars, n=6). Preliminary results indicate that hexamethonium and CBD tended to increase the ability of the mesenteric bed to accommodate volume (hexamethonium: +1.9±1.5, n=6; CBD: +0.8±0.6ml, n=3).We show that SHR have higher venous tone and reduced capacity to accommodate excess volume within the mesenteric vascular bed. Reductions in sympathetic drive reduced venous tone and improved the ability to accommodate volume load. Inhibiting sympathetic activity may provide a novel therapeutic opportunity to restore venous mesenteric capacity and potentially ameliorate hypertension. Marsden Fund, Royal Society of New Zealand; Health Research Council of New Zealand This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.