The gender differences in the relaxation to levosimendan of human internal mammary artery.

PURPOSE: The mechanism of the vasorelaxation to levosimendan varies depending on the vascular bed and species studied. Here, we examined the vasorelaxation to levosimendan as well as its modification by various potassium channel antagonists in human internal mammary artery (IMA) obtained from male and female patients.

METHODS

IMA grafts were supplied from 27 male and 19 age-matched female patients undergoing coronary bypass operation. The contraction to noradrenaline and relaxation to levosimendan were studied in IMA rings obtained from both gender. The relaxations to levosimendan were also assessed in the presence of glibenclamide (10 microM), an adenosine triphosphate-sensitive potassium channel (K(ATP)) blocker, or charybdotoxin (100 nM), a calcium-activated potassium channel (K(Ca)) blocker, or 4-aminopyridine(1 mM), a voltage-sensitive potassium channel (K(v)) inhibitor.

RESULTS

Concentration-response curves to noradrenaline were not different in IMA rings from either gender. Pretreatment with levosimendan (3 x 10(-7) M) slightly modified the contractions to noradrenaline in both gender. Levosimendan (10(-9)-10(-5) M) produced concentration-dependent relaxation in IMA rings, contracted by noradrenaline (5 x 10(-6) M), from males and females. The vasodilatory effects of levosimendan were more pronounced in the arteries from males (83%) than females (69%), in term of the maximal relaxation (E (max)). Charybdotoxin and glibenclamide significantly inhibited the relaxation to levosimendan in the arteries from males but not in those of females.

CONCLUSIONS

The vasodilating efficacy of levosimendan and its relaxation mechanism differs between the arteries from males and females, which may have clinical consequences in the treatment of heart failure.