Venous endothelin receptor function in patients with chronic heart failure

Area of Science:

• Cardiovascular Physiology
• Pharmacology
• Medical Research

Background:

• Cardiac preload reduction via venodilation benefits chronic heart failure (CHF).
• Endothelin receptor antagonists are a potential CHF therapy, necessitating understanding of endothelin-1's venoconstrictor role in CHF.
• Human blood vessels possess two main endothelin receptor subtypes: ET(A) and ET(B).

Purpose of the Study:

• To investigate the in vivo venoconstrictor effects of endothelin-1 and sarafotoxin S6c in patients with CHF and healthy controls.
• To determine the roles of ET(A) and ET(B) receptors in mediating venoconstriction in CHF.

Main Methods:

• Locally active doses of endothelin-1 (non-selective ET(A)/ET(B) agonist) or sarafotoxin S6c (selective ET(B) agonist) were infused into a dorsal hand vein for 1 hour.
• Venous internal diameter was measured using a displacement technique in patients with CHF and age-matched healthy controls.
• Comparisons were made between the groups regarding the peak reduction in vein calibre.

Main Results:

• Venoconstriction to endothelin-1 was significantly blunted in CHF patients (26+/-7% reduction) compared to controls (51+/-6% reduction).
• Venoconstriction to sarafotoxin S6c was similar in both CHF patients (17+/-5% reduction) and controls (17+/-4% reduction).
• Both ET(A) and ET(B) receptors mediate venoconstriction in both healthy subjects and CHF patients.

Conclusions:

• Chronic heart failure may involve a selective decrease in venous ET(A) receptor sensitivity.
• Optimal inhibition of endothelin-1's venoconstrictor effects in CHF might require an antagonist blocking both ET(A) and ET(B) receptors.
• Further research is needed to clarify the functional significance of altered venous ET(A) receptor sensitivity in CHF.