Chronic exercise normalizes changes in Ca _v1.2 and K_Ca 1.1 channels in mesenteric arteries from spontaneously hypertensive rats

Background and Purpose Regular physical activity is an effective non-pharmacological therapy for prevention and control of hypertension. However, the underlying mechanisms are not fully understood. Accumulating evidence shows that the elevated vascular tone in hypertension is a consequence of the 'ion channel remodelling' that occurs during sustained high BP. The present study investigated the effects of aerobic exercise on the electrical remodelling of L-type Ca²⁺ (Ca_v1.2) and large-conductance Ca²⁺-activated K⁺ (K_Ca1.1) channels in mesenteric arteries (MAs) from spontaneously hypertensive rats (SHRs). Experimental Approach SHRs and normotensive (Wistar-Kyoto) rats were subjected to aerobic training or kept sedentary, and vascular mechanical and functional properties were evaluated. Key Results Exercise did not affect the heart weight, but reduced the heart rate and body weight in SHR. In mesenteric arterial myocytes, exercise normalized the increased Ca_v1.2 and K_Ca1.1 current density in SHRs. Exercise also ameliorated the increased open probability and mean open time of the single K_Ca1.1 channel in hypertension. The isometric contraction study revealed that both nifedipine (Ca_v1.2 channel blocker) and NS11021 (K_Ca1.1 channel activator) induced concentration-dependent vasorelaxation in MAs precontracted with noradrenaline. Exercise normalized the increased sensitivity of tissues to nifedipine and NS11021 in SHR. Furthermore, protein expression of the Ca_v1.2 α_1C-subunit together with the K_Ca1.1 α- and β1-subunit was significantly increased in SHRs; and exercise ameliorated these molecular alterations in hypertension. Conclusions and Implications Chronic exercise reduces BP and restores vascular function in MAs from SHR, which might be related to the correction of the Ca_v1.2 and K_Ca1.1 channel remodelling during hypertension.