Improved myocardial beta-adrenergic responsiveness and signaling with exercise training in hypertension

Article

关键词: LEFT-VENTRICULAR HYPERTROPHY;    HEART-FAILURE;    RAT-HEART;    CONTRACTILE RESPONSE;    CARDIAC-HYPERTROPHY;    ENHANCED EXPRESSION;    REGULATORY PROTEIN;    ADENYLATE-CYCLASE;    G(I) PROTEINS;    RECEPTORS;   

DOI  :  10.1161/CIRCULATIONAHA.104.505784

来源: SCIE

【 摘 要 】

Background - Cardiac responses to beta- adrenergic receptor stimulation are depressed with pressure overload - induced cardiac hypertrophy. We investigated whether exercise training could modify beta- adrenergic receptor responsiveness in a model of spontaneous hypertension by modifying the beta- adrenergic receptor desensitizing kinase GRK2 and the abundance and phosphorylation of some key Ca2+ cycling proteins. Methods and Results - Female spontaneously hypertensive rats ( SHR; age, 4 months) were placed into a treadmill running ( SHR- TRD; 20 m/ min, 1 h/ d, 5 d/ wk, 12 weeks) or sedentary group ( SHR- SED). Age- matched Wistar Kyoto ( WKY) rats were controls. Mean blood pressure was higher in SHR versus WKY ( P < 0.01) and unaltered with exercise. Left ventricular ( LV) diastolic anterior and posterior wall thicknesses were greater in SHR than WKY ( P < 0.001) and augmented with training ( P < 0.01). Langendorff LV performance was examined during isoproterenol ( ISO) infusions ( 1 x 10(-10) to 1 x 10(-7) mol/ L) and pacing stress ( 8.5 Hz). The peak LV developed pressure/ ISO dose response was shifted rightward 100- fold in SHR relative to WKY. The peak ISO LV developed pressure response was similar between WKY and SHR- SED and increased in SHR- TRD ( P < 0.05). SHR- TRD showed the greatest lusitropic response to ISO ( P < 0.05) and offset the pacing- induced increase in LV end- diastolic pressure and the time constant of isovolumic relaxation ( tau) observed in WKY and SHR- SED. Improved cardiac responses to ISO in SHR- TRD were associated with normalized myocardial levels of GRK2 ( P < 0.05). SHR displayed increased L- type Ca2+ channel and sodium calcium exchanger abundance compared with WKY ( P < 0.001). Training increased ryanodine receptor phosphorylation and phospholamban phosphorylation at both the Ser(16) and Thr(17) residues ( P < 0.05). Conclusions - Exercise training in hypertension improves the inotropic and lusitropic responsiveness to beta adrenergic receptor stimulation despite augmenting LV wall thickness. A lower GRK2 abundance and an increased phosphorylation of key Ca2+ cycling proteins may be responsible for the above putative effects.

【 授权许可】

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