Exercise Training Increases L-Type Calcium Current Density in Coronary Smooth Muscle

Bowles, Douglas K.; Hu, Q.; Laughlin, M. Harold; Sturek, Michael

doi:10.1097/00005768-199805001-00226

Cited by 24 publications

(48 citation statements)

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“…[29][30][31]33,34 Some previous studies have also investigated the effects of exercise on the Ca v 1.2 channels in specific arteries from normal animals. Bowles et al 35 demonstrated that the smooth muscle L-type Ca 2+ current density is increased within the coronary arterial bed by endurance exercise training in miniature swines. This increased voltage-gated calcium channel density may provide an important mechanistic link between functional and cellular adaptations in the coronary circulation in response to exercise training.…”

Section: Discussionmentioning

confidence: 99%

Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats

Chen

Zhang

et al. 2015

Hypertens Res

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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+) (Cav1.2) channels on the plasma membrane of vascular smooth muscle cells have a pivotal role in modulating the vascular tone, and the upregulation of Cav1.2 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 Cav1.2 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, Cav1.2 channel current density and Cav1.2 α1C-subunit protein expression in MAs from SHRs. However, high-intensity exercise training aggravated all of these hypertension-associated functional and molecular alterations of Cav1.2 channels. These results indicate that moderate-intensity aerobic training may act as a drug and effectively reverse the remodeling of Cav1.2 channels in hypertension to restore the vascular function in MAs, but that high-intensity exercise exaggerates the adverse remodeling of Cav1.2 channels and worsens the vascular function.

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Section: Discussionmentioning

confidence: 99%

Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats

Chen

Zhang

et al. 2015

Hypertens Res

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“…Freshly dispersed CASM cells were obtained as described previously (3,5,6,18). RCA were opened longitudinally and pinned, lumen side up, onto a silicone rubber substratum in ϳ2 ml of low-Ca 2ϩ solution.…”

Section: Methodsmentioning

confidence: 99%

Endogenous testosterone increases L-type Ca²⁺ channel expression in porcine coronary smooth muscle

Bowles¹,

Maddali²,

Ganjam³

et al. 2004

American Journal of Physiology-Heart and Circulatory Physiology

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Evidence indicates that gender and sex hormonal status influence cardiovascular physiology and pathophysiology. We recently demonstrated increased L-type voltage-gated Ca2+ current (ICa,L) in coronary arterial smooth muscle (CASM) of male compared with female swine. The promoter region of the L-type voltage-gated Ca2+ channel (VGCC) (Cav1.2) gene contains a hormone response element that is activated by testosterone. Thus the purpose of the present study was to determine whether endogenous testosterone regulates CASM ICa,L through regulation of VGCC expression and activity. Sexually mature male and female Yucatan swine (7-8 mo; 35-45 kg) were obtained from the breeder. Males were left intact (IM, n=8), castrated (CM, n=8), or castrated with testosterone replacement (CMT, n=8; 10 mg/day Androgel). Females remained gonad intact (n=8). In right coronary arteries, both Cav1.2 mRNA and protein were greater in IM compared with intact females. Cav1.2 mRNA and protein were reduced in CM compared with IM and restored in CMT. In isolated CASM, both peak and steady-state ICa were reduced in CM compared with IM and restored in CMT. In males, a linear relationship was found between serum testosterone levels and ICa. In vitro, both testosterone and the nonaromatizable androgen, dihydrotestosterone, increased Cav1.2 expression. Furthermore, this effect was blocked by the androgen receptor antagonist cyproterone. We conclude that endogenous testosterone is a primary regulator of Cav1.2 expression and activity in coronary arteries of males.

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“…Isolated CSM cells were obtained by enzymatic dispersion for voltage-clamp experiments as described previously [24][25][26]. Cell suspensions were stored in low Ca 2+ (0.1 mM) buffer at 4 8C until use (0-6 h).…”

Section: Whole-cell Voltage Clampmentioning

confidence: 99%

“…Cell suspensions were stored in low Ca 2+ (0.1 mM) buffer at 4 8C until use (0-6 h). Whole-cell VGCC currents were determined using a standard wholecell voltage-clamp technique [24][25][26][27]. Following whole-cell configuration, the superfusate was switched to PSS with tetraethylammonium chloride (TEACl) substitution for NaCl and 10 mM Ba 2+ as the charge carrier.…”

Section: Whole-cell Voltage Clampmentioning

confidence: 99%

Exaggerated coronary vasoreactivity to endothelin-1 in aged rats: Role of protein kinase C

Muller‐Delp

Dougherty

Heaps

et al. 2005

Cardiovascular Research

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Exercise Training Increases L-Type Calcium Current Density in Coronary Smooth Muscle

Cited by 24 publications

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Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats

Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats

Endogenous testosterone increases L-type Ca²⁺ channel expression in porcine coronary smooth muscle

Exaggerated coronary vasoreactivity to endothelin-1 in aged rats: Role of protein kinase C

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Exercise Training Increases L-Type Calcium Current Density in Coronary Smooth Muscle

Cited by 24 publications

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Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats

Exercise intensity-dependent reverse and adverse remodeling of voltage-gated Ca2+ channels in mesenteric arteries from spontaneously hypertensive rats

Endogenous testosterone increases L-type Ca2+ channel expression in porcine coronary smooth muscle

Exaggerated coronary vasoreactivity to endothelin-1 in aged rats: Role of protein kinase C

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Endogenous testosterone increases L-type Ca²⁺ channel expression in porcine coronary smooth muscle