Background: Aging is the main risk factor for cardiovascular disease, which remains the number one killer in modern society. As age advances, several structural and functional changes
occur in the vasculature. In contrast to age, habitual exercise is associated with enhanced vascular function and reduced risk of cardiovascular disease. However, the underlying mechanisms are not
fully understood. Large-conductance Ca2+-activated K+ (MaxiK) channels are expressed broadly on smooth muscle cells (SMCs) and play a critical role in regulating vascular tone. This study was designed
to determine the effects of aerobic exercise training on aging-associated selective changes of the function and expression of MaxiK channels in mesenteric arteries.
Methods: Male Wistar rats aged 19–21 months were randomly assigned to sedentary (O-SED) and exercise-trained groups (O-EX). Two-monthold rats were used as Young control.
Results: Addition of iberiotoxin (10−8 M) increased the norepinephrine-induced arterial contraction in all three groups, with the greatest enhancement being in Young and the least in
O-SED. Patch clamp study revealed the characteristics of aging on MaxiK channel function in mesenteric arteries, mainly including (a) decrease of iberiotoxin-sensitive whole-cell K+ current, (b)
decrease of open probability and Ca2+/voltage sensitivity of single MaxiK channel, and (c) reduction of tamoxifen-induced MaxiK activation. After exercise training, all of these changes were markedly
inhibited. Western blotting revealed that the protein expression of MaxiK was significantly reduced with aging and the suppression of β1-subunit was larger than that of α-subunit, although exercise
training diminished this alteration.
Conclusions: Taken together, aerobic exercise training reverses the aging-related unparallel downregulation of MaxiK α- and β1-subunit expression on mesenteric arteries, which partly
underlies the beneficial effect of exercise on restoring aging-associated reduction in mesenteric artery vasodilatory properties.