Authors: Tomonori Hattori

Abstract

Background:

Endothelium-derived hyperpolarizing factor (EDHF) is a major mediator of endothelium-dependent vasorelaxation in small resistance arteries and is crucial for microcirculatory regulation. Sepsis causes endothelial injury and profound microcirculatory dysfunction, yet the time course of EDHF function during sepsis remains unclear.

Methods:

Male Wistar rats received intraperitoneal lipopolysaccharide (LPS) 5 mg/kg. Mesenteric and right gastroepiploic arteries were harvested at baseline (Control), 24 h (Day 1), and 72 h (Day 3). Vasorelaxation was assessed by acetylcholine (ACh)–induced relaxation in small arteries and by recording smooth muscle membrane potential (hyperpolarization). To examine nitric oxide (NO) contribution, experiments were repeated with the NO synthase inhibitor nitro-L-arginine (L-NNA).

Results:

ACh-induced vasorelaxation was markedly suppressed on Day 1 versus Control, accompanied by reduced endothelial hyperpolarization, indicating early impairment of EDHF-associated responses. By Day 3, vasorelaxation and hyperpolarization recovered toward baseline. However, under NO inhibition with L-NNA, the Day 3 recovery was abolished, suggesting compensatory NO-dependent relaxation when EDHF function is compromised.

Conclusion:

In LPS-induced sepsis, EDHF-associated vasorelaxation and hyperpolarization are transiently impaired early and recover later, while NO can compensate during EDHF dysfunction. This dynamic interplay between EDHF and NO may represent a therapeutic target to improve microcirculatory disturbances in sepsis.

Keywords: EDHF, sepsis, endothelium