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

Abstract

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 (Kv) participates more in males. Inhibition of the three types of Ca2+-activated K+ channels induced a greater reduction in Rmax 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 Ca2+-activated K+ channels (BKCa) in females and Kv in males and in the K+-induced relaxation and the Na+K+-ATPase vascular functional activity is greater in males.

Changes in cardiac Na+/K+-ATPase expression and activity in female rats fed a high-fat diet

“…Here we show that in female rats a HF diet reduces the expression of the ɑ1 subunit of Na + /K + -ATPase, but does not affect the expression of ɑ2 subunit or the Na + /K + -ATPase activity. Numerous studies show significant gender differences in the relative amount of α1 and α2 catalytic isoforms and the activity of Na + -K + -ATPase [44,24,45,46]. In our study, unaltered Na + /K + -ATPase activity despite the reduced content of its ɑ1 subunit may be explained by the fact that rodent α1-subunit isoform has a very low affinity to ouabain, and ouabain-sensitive methods largely reflect the α2-subunit content [47,48].…”

Neuronal Voltage Gated Potassium Channels May Modulate Nitric Oxide Synthesis in Corpus Cavernosum

“…In the present study, treatment of rabbit CC with the K V blocker, 4-AP, reduced the SNP and ACh-induced relaxations, an effect which indicates a role for K V channels in mediating NO action. The blockade of K V channels also attenuated SNP and ACh-induced relaxations in rat aorta (Satake et al, 1997 ; Fiorim et al, 2012 ; Dias et al, 2014 ; Oliveira et al, 2014 ). In line with these observations, K V channels have been implicated in the ACh-induced increase in ICP in cats as described by Moon et al ( 1999 ).…”

Menopause and Ischemic Stroke: A Brief Review

“…Blocking NKA with ouabain (OUA) increases vascular tone [41] moreover, reduces Ach-induced vascular relaxation in the aorta of both male and female rats, but less so in females suggesting lower NKA functional activity in females [42]. In another study, ovariectomized female rats do not exhibit differences in NKA function compared to the male counterparts, and chronic hormone replacement with 17β-estradiol restored the vasodilator effect of Ach on NKA [43].…”