Forgotten Circulation: Reduced Mesenteric Venous Capacitance in Hypertensive Rats Is Improved by Decreasing Sympathetic Activity

Author(s)

Emans, Tonja W. ; Moraes, Davi J. A. ; Ben-Tal, Alona ; Barrett, Carolyn J. ; Paton, Julian F. R. ; McBryde, Fiona D.

• Document type: Journal article
• Source: Hypertension; v. 81, n. 4, p. 13-pg., 2024-04-01.

Abstract

BACKGROUND: The mesenteric venous reservoir plays a vital role in mediating blood volume and pressure changes and is richly innervated by sympathetic nerves; however, the precise nature of venous sympathetic regulation and its role during hypertension remains unclear. We hypothesized that sympathetic drive to mesenteric veins in spontaneously hypertensive (SH) rats is raised, increasing mean circulatory filling pressure (MCFP), and impairing mesenteric capacitance. METHODS: Arterial pressure, central venous pressure, mesenteric arterial, and venous blood flow were measured simultaneously in conscious male Wistar and SH rats. MCFP was assessed using an intraatrial balloon. Hemodynamic responses to volume changes (+/- 20%) were measured before and after ganglionic blockade and carotid body denervation. Sympathetic venoconstrictor activity was measured in situ. RESULTS: MCFP in vivo (10.8 +/- 1.6 versus 8.0 +/- 2.1 mm Hg; P=0.0005) and sympathetic venoconstrictor drive in situ (18 +/- 1 versus 10 +/- 2 mu V; P<0.0001) were higher in SH rats; MCFP decreased in SH rats after hexamethonium and carotid body denervation (7.6 +/- 1.4; P<0.0001 and 8.5 +/- 1.0 mm Hg; P=0.0045). During volume changes, arterial pressure remained stable. With blood loss, net efflux of blood from the mesenteric bed was measured in both strains. However, during volume infusion, we observed net influx in Wistar (+2.3 +/- 2.6 mL/min) but efflux in SH rats (-1.0 +/- 1.0 mL/min; P=0.0032); this counterintuitive efflux was abolished by hexamethonium and carotid body denervation (+0.3 +/- 1.7 and 0.5 +/- 1.6 mL/min, respectively). CONCLUSIONS: In SH rats, excessive sympathetic venoconstriction elevates MCFP and reduces capacitance, impairing volume buffering by mesenteric veins. We propose selective targeting of mesenteric veins through sympathetic drive reduction as a novel therapeutic opportunity for hypertension. (AU)

• FAPESP's process: 21/06886-7 - Role of purinergic receptors in the carotid body in heart failure
• Grantee: Davi José de Almeida Moraes
• Support Opportunities: Research Grants - Young Investigators Grants - Phase 2