Gender differences in vascular reactivity to levosimendan in rat aortic rings

Objectives: The calcium sensitizer, levosimendan exerts inotropic and vasodilatory properties and is currently used to treat heart failure and vascular dysfunction. As gender differences in vascular function are widely described, we investigated, how far gender differences may play a role in the vascular responses to levosimendan.

Material and Methods: Thoracic aortic rings from age-matched male and female rats were immersed in isolated organ bath, superfused by oxygenated Krebs-Henseleit solution and precontracted by phenylephrine. The dose-dependent vasoresponse to levosimendan was investigated in intact (group 1) and in de-endothelized (group 2) rings. All values are given as mean±SEM at ED75.

Results: Application of levosimendan resulted in a significantly (two-fold) higher vasodilatation in females in comparison to males in both group 1 (70±7% vs. 33±8% p=0.00743) and group 2 (69±7% vs. 26±4%, p=0.00159). While de-endothelization did not influence the response to levosimendan in females, the vasodilatory response was decreased in males after de-endothelization (p<0.05).

Conclusions: Characteristic gender-dependent differences in the vascular response to levosimendan could be documented: 1) the vascular response to levosimendan in females is more profound and 2) the presence of intact endothelium may contribute to the vasodilatory effects of levosimendan in males. These findings should be taking into account for calculation of effective doses of levosimendan in male and female patients.