Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca 2+ channels in mesenteric arteries from spontaneously hypertensive rats

Abstract

Exercise can be regarded as a drug for treating hypertension, and the 'dosage' (intensity/volume) is therefore of great importance. L-type voltage-gated Ca 2+ (Ca v 1.2) channels on the plasma membrane of vascular smooth muscle cells have a pivotal role in modulating the vascular tone, and the upregulation of Ca v 1.2 channels is a hallmark feature of hypertension. The present study investigated the beneficial and adverse effects of exercise at different intensities on the remodeling of the Ca v 1.2 channel in mesenteric arteries (MAs) of spontaneously hypertensive rats (SHRs). Moderate-(SHR-M, 18-20 m min-1) and high-intensity (SHR-H, 26-28 m min-1) aerobic exercise training groups were created for SHRs and lasted for 8 weeks (1 h per day, 5 d per week). Age-matched sedentary SHRs and normotensive Wistar-Kyoto rats (WKY) were used as controls. The mesenteric arterial mechanical and functional properties were evaluated. Moderate-intensity exercise training induced a lower systolic blood pressure and heart rate in these rats compared with sedentary SHRs. BayK 8644 and nifedipine induced vasoconstriction and dose-dependent vasorelaxation, respectively, in the mesenteric arterial rings. Moderate-intensity exercise significantly suppressed the increase in BayK 8644-induced vasoconstriction, tissue sensitivity to nifedipine, Ca v 1.2 channel current density and Ca v 1.2 α1C-subunit protein expression in MAs from SHRs. However, high-intensity exercise training aggravated all of these hypertension-associated functional and molecular alterations of Ca v 1.2 channels. These results indicate that moderate-intensity aerobic training may act as a drug and effectively reverse the remodeling of Ca v 1.2 channels in hypertension to restore the vascular function in MAs, but that high-intensity exercise exaggerates the adverse remodeling of Ca v 1.2 channels and worsens the vascular function.