Aerobic Exercise Inhibits The Functional Remodeling Of Ca_L Channels In Mesenteric Arteries From Spontaneously Hypertensive Rats

Purpose:L type Ca2+ channels (CaL) are the main channels of Ca2+ channels in vascular smooth muscle cells (VSMC), which decide excitation-contraction coupling of VSMC, and possess the function of regulating cell contraction and relaxation. As is known to all, aerobic exercise can regulate blood pressure, while the underlying ion channel mechanisms are not fully understood. This study aims to investigate the effects of aerobic exercise on the functional remodeling of the CaL channels in rat mesenteric artery smooth muscle cells from spontaneously hypertensive rats.Methods:Twelve-week-old male normotensive Wistar-Kyoto rats (WKY, n=24) and SHRs (n=24) were used. Animals both in the normotensive group and hypertension group were randomly assigned into two groups respectively:sedentary group (WKY-SED, n=12; SHR-SED, n=12) and exercise-trained group (WKY-EX, n=12; SHR-EX, n=12). For exercise-trained group, exercise training was performed on a motor treadmill (20m/min,60min/d,5d/w). After 8 weeks, the mesenteric arteries were removed, vascular contractility of mesenteric arteries(MAs) was measured. VSMC were obtained by using enzymatic isolation method. CaL channels current was examined by using whole cell patch clamp recording technique. Besides, CaL channels alC subunit protein expression of MAs were observed by immunohistochemical staining.Result:1) Hypertension was associated with the increase of the heart weight, systolic blood pressure, diastolic blood pressure, mean arterial pressure, and heart rate. Exercise not only decreased the systolic blood pressure, diastolic blood pressure, mean arterial pressure and heart rate of the SHR, but also reduced the weight and decrease the systolic blood pressure of normotensive rats.2) The response to Bay K8644(Ca channel activator) of SHR-SED group and WKY-EX group showed a significant increase compared with the WKY-SED group. And the SHR-EX group exhibited an obvious decrease in reaction to Bay K8644 compared with the SHR-SED group.3) The sensitivity to Nifedipine(CaL channel inhibitor) of SHR-SED group and WKY-EX group is strong than that of the WKY-SED group. In comparison to the SHR-SED group, the sensitivity to Nifedipine in SHR-EX group decreased significantly.4)The recorded current magnitude decreased when added in activator Bay K8644 and the current was blocked by Nifedipine. Inactivation and activation curves showed voltage-dependent feature.5) The current magnitude of SHR-SED group exhibited an increase compared to the WKY-SED group and the current magnitude of the SHR-EX group decreased obviously in contrast with the SHR-SED group.6) There was no significant difference of the membrane capacitance among groups. The current density in SHR-SED group and WKY-EX group were extremely higher than that of the WKY-SED group. Compared with the SHR-SED group, the current density of SHR-EX group showed a significant decrease.7) Both of the voltage dependence activation and inactivation curves were not significantly different among four groups. No differences of the slopes and Vh were observed.8) The alC fluorescence intensity of both SHR-SED and WKY-EX group higher than that of WKY-SED group. Compared with SHR-SED group, the α1C fluorescence intensity of SHR-EX group was weaker.Conclusion:Hypertension induces functional upregulation of CaL channels in mesenteric arterial smooth muscle cells, while regular aerobic exercise significantly inhibits such increase, which may be one of the important mechanisms underlying the effectiveness of exercise on lowering high blood pressure.