Increased EETs participate in peripheral endothelial dysfunction of cirrhosis

Area of Science:

• Cardiovascular Physiology
• Hepatology
• Pharmacology

Background:

• Cirrhosis leads to hyperdynamic circulation and portal hypertension.
• Epoxyeicosatrienoic acids (EETs), produced by P450 enzymes, are potent vasodilators.
• EETs play a role in regulating peripheral blood flow.

Purpose of the Study:

• To evaluate plasma EET levels in cirrhotic patients.
• To investigate the effects of epoxygenase and nitric oxide synthase (NOS) inhibition on skin blood flow in normal and cirrhotic subjects.
• To elucidate the role of EETs in the pathophysiology of cirrhosis-associated circulatory changes.

Main Methods:

• Measurement of plasma free EET levels in cirrhotic patients and healthy controls.
• Assessment of skin blood flow using laser Doppler flowmetry.
• Pharmacological inhibition of epoxygenase (miconazole) and NOS (L-NAME) in vivo.

Main Results:

• Plasma EET levels were elevated in cirrhotic patients.
• Skin blood flow was increased in cirrhotic patients without ascites but reduced in those with ascites.
• Inhibition of epoxygenase and NOS significantly decreased skin blood flow, with a more pronounced effect in cirrhotic patients.

Conclusions:

• EETs are implicated in the control of peripheral circulation in healthy individuals.
• EETs contribute to the pathophysiology of peripheral vasodilation in cirrhotic patients, particularly those with ascites.
• Combined inhibition of epoxygenase and NOS further reduced peripheral blood flow, underscoring the synergistic roles of these pathways.