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- W3040904037 abstract "Regular exercise is a lifestyle intervention for controlling hypertension and has an improving effect on vascular function. Voltage-gated L-type Ca2+ (LTCC) and large-conductance Ca2+-activated K+ (BKCa) channels are two principal mediators of vascular smooth muscle contractility and arterial tone. Exercise-induced LTCC and BKCa channel alterations in arterial myocytes may contribute to the improvement of vascular function in pathological conditions. However, the mechanism underlying the functional changes of these ion channels is still unclear but critical for understanding the mechanistic basis of reliable arterial performance. PURPOSE: To investigate the role of DNA methylation in exercise-induced reprogramming of LTCC and BKCa channel in mesenteric arteries from spontaneously hypertensive rats (SHRs). METHODS: Twelve-week-old male SHRs and normotensive Wistar-Kyoto rats (WKYs) were assigned into sedentary and exercise groups. Exercise groups were performed a moderate-intensity treadmill running (about 55-65% of maximal aerobic velocity, 20 m/min, 0% grade, 60 min, 5 days/week). After 12 weeks, patch clamp study, Western blot, qPCR and bisulfite sequencing PCR were used to detect the LTCC and BKCa channel currents, protein expression and mRNA level of LTCC α1c and BKCa β1 subunits, DNA methylation level of α1c and β1 gene promoter region. RESULTS: Exercise training significantly decreased the systolic blood pressure in both WKYs (139.5±0.48 vs. 132.3±0.56 mmHg, P<0.05) and SHRs (199.4±0.45 vs. 191.2±0.71 mmHg, P<0.05). Exercise inhibited hypertension-induced upregulation of LTCC (−16.0±1.6 vs. −11.4±1.5 pA/pF, P<0.05) and BKCa (43.7±2.8 vs. 23.1±1.6 pA/pF, P<0.05) channel current density of mesenteric arterial myocytes by repressing LTCC α1c (2.8±0.3 vs. 1.7±0.2, P<0.05) and BKCa β1 (1.7±0.3 vs. 0.8±0.2, P<0.05) subunit expression. DNA bisulfite sequencing PCR showed that chronic exercise increased CpG methylation at α1c (81.3±1.6 vs. 87.9±0.8%, P<0.05) and β1 (17.7±0.4 vs. 25.2±2.0%, P<0.05) gene promoter in SHR mesenteric arteries. CONCLUSION: Exercise suppresses LTCC and BKCa channel function via hypermethylation of α1c and β1 subunits, which contributes to the restoration of mesenteric arterial function and vasodilation during hypertension." @default.
- W3040904037 created "2020-07-16" @default.
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- W3040904037 date "2020-07-01" @default.
- W3040904037 modified "2023-09-27" @default.
- W3040904037 title "Exercise Mediates Epigenetic Suppression Of LTCC And Bk Ca Channel In Mesenteric Arteries Of Hypertensive Rats" @default.
- W3040904037 doi "https://doi.org/10.1249/01.mss.0000685280.69614.e9" @default.
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