Na(+)K(+)-ATPase Activity and K(+) Channels Differently Contribute to Vascular Relaxation in Male and Female Rats

Gender associated differences in vascular reactivity regulation might contribute to the low incidence of cardiovascular disease in women. Cardiovascular protection is suggested to depend on female sex hormones’ effects on endothelial function and vascular tone regulation. We tested the hypothesis that potassium (K(+)) channels and Na(+)K(+)-ATPase may be involved in the gender-based vascular reactivity differences. Aortic rings from female and male rats were used to examine the involvement of K(+) channels and Na(+)K(+)-ATPase in vascular reactivity. Acetylcholine (ACh)-induced relaxation was analyzed in the presence of L-NAME (100 µM) and the following K(+) channels blockers: tetraethylammonium (TEA, 2 mM), 4-aminopyridine (4-AP, 5 mM), iberiotoxin (IbTX, 30 nM), apamin (0.5 µM) and charybdotoxin (ChTX, 0.1 µM). The ACh-induced relaxation sensitivity was greater in the female group. After incubation with 4-AP the ACh-dependent relaxation was reduced in both groups. However, the dAUC was greater in males, suggesting that the voltage-dependent K(+) channel (K(v)) participates more in males. Inhibition of the three types of Ca(2+)-activated K(+) channels induced a greater reduction in R(max) in females than in males. The functional activity of the Na(+)K(+)-ATPase was evaluated by KCl-induced relaxation after L-NAME and OUAincubation. OUA reduced K(+)-induced relaxation in female and male groups, however, it was greater in males, suggesting a greater Na(+)K(+)-ATPase functional activity. L-NAME reduced K(+)-induced relaxation only in the female group, suggesting that nitric oxide (NO) participates more in their functional Na(+)K(+)-ATPase activity. These results suggest that the K(+) channels involved in the gender-based vascular relaxation differences are the large conductance Ca(2+)-activated K(+) channels (BK(Ca)) in females and K(v) in males and in the K(+)-induced relaxation and the Na(+)K(+)-ATPase vascular functional activity is greater in males.