The Gender Differences in the Relaxation to Levosimendan of Human Internal Mammary Artery
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.
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 μM), an adenosine triphosphate-sensitive potassium channel (KATP) blocker, or charybdotoxin (100 nM), a calcium-activated potassium channel (KCa) blocker, or 4-aminopyridine(1 mM), a voltage-sensitive potassium channel (Kv) inhibitor.
Concentration–response curves to noradrenaline were not different in IMA rings from either gender. Pretreatment with levosimendan (3 × 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 × 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.
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.
Key wordslevosimendan gender human artery potassium channels relaxation
This paper is supported by the Gazi University Research Fund (BAP 02/2006-10).
- 19.Akar F, Uydes-Dogan BS, Tufan H, Aslamaci S, Koksoy C, Kanzik I. The comparison of the responsiveness of human isolated internal mammary and gastroepiploic arteries to levcromakalim: an alternative approach to the management of graft spasm. Br J Clin Pharmacol 1997;44:49–56.PubMedCrossRefGoogle Scholar
- 23.Lilleberg J, Nieminen MS, Akkila J, Heikkiläc L, Kuitunend A, Lehtonen L, et al. Effects of a new calcium sensitizer, levosimendan, on haemodynamics, coronary blood flow and myocardial substrate utilization early after coronary artery bypass grafting. Eur Heart J 1998;19:660–8.PubMedCrossRefGoogle Scholar
- 34.Teede H, van der Zypp A, Majewski H. Gender differences in protein kinase G-mediated vasorelaxation of rat aorta. Clin Sci (Lond.) 2001;100:473–9.Google Scholar