Exercise training improves systolic function in hypertensive myocardium

Abstract

The general purpose of this study was to test the effect of exercise training on the left ventricular (LV) pressure-volume relationship (LV/PV) and apoptotic signaling markers in normotensive and hypertensive hearts. Four-month-old female normotensive Wistar-Kyoto rats (WKY; n = 37) and spontaneously hypertensive rats (SHR; n = 38) were assigned to a sedentary (WKY-SED, n = 21; SHR-SED, n = 19) or treadmill-trained (WKY-TRD, n = 16; SHR-TRD, n = 19) group (∼60% Vo(2 peak), 60 min/day, 5 days/wk, 12 wk). Ex vivo LV/PV were established in isovolumic Langendorff-perfused hearts, and LV levels of Akt, phosphorylated Akt (Akt(Pi)), Bad, phosphorylated Bad (Bad(Pi)) c-IAP, x-IAP, calcineurin, and caspases 3, 8, and 9 were measured. Heart-to-body weight ratio was increased in SHR vs. WKY (P < 0.05), concomitant with increased calcineurin mRNA (P < 0.05). There was a rightward shift in the LV/PV (P < 0.05) and a reduction in systolic elastance (E(s)) in SHR vs. WKY. Exercise training corrected E(s) in SHR (P < 0.05) but had no effect on the LV/PV in WKY. Caspase 3 was increased in SHR-SED relative to WKY-SED, while Bad(Pi,) c-IAP, and x-IAP were significantly lower in SHR relative to WKY (P < 0.05). Exercise training increased Bad(Pi) in both WKY and SHR but did not alter caspase 9 activity in either group. While caspase 3 activity was increased with training in WKY (P < 0.05), it was unchanged with training in SHR. We conclude that moderate levels of regular aerobic exercise attenuate systolic dysfunction early in the compensatory phase of hypertrophy, and that a differential phenotypical response to moderate-intensity exercise exists between WKY and SHR.

Fig. 1.

Left ventricular (LV) systolic and LV diastolic pressure (LVEDP)-volume relationships. Systolic and end-diastolic pressure-volume relationships in Wistar-Kyoto rats (WKY; top) and spontaneously hypertensive rats (SHR; bottom) are illustrated. The LVEDP-pressure relationship (LVEDP/V) was shifted slightly rightward in SHR relative to WKY (main effect; P < 0.05) but was not statistically different between exercise-trained (TRD) and sedentary (SED) animals of either strain. The depressed slope of the end-systolic pressure volume relationship (systolic elastance, E_s) in SHR-SED was improved with training (SHR-TRD). Data are presented as means ± SE.

Fig. 2.

E_s in WKY and SHR. E_s was depressed in SHR relative to WKY (main effect; P < 0.05) but improved with training in SHR (P < 0.05). Data are presented as means ± SE. *P < 0.05 for SHR-SED vs. SHR-TRD.

Fig. 3.

Abundance of key apoptotic signaling molecules in WKY and SHR. The abundance of Akt (A) was significantly higher in SHR-SED vs. the other groups (P < 0.05; following a significant interaction effect), while phosphorylated Akt (Akt_Pi) (B) was similar across groups. Bad (C) was also similar across groups, but phosphorylated Bad (Bad_Pi) was lower in SHR vs. WKY (D) (main effect; P < 0.05). Exercise training increased Bad_Pi in both WKY and SHR (P < 0.05; following a significant main effect; D). Both c-IAP (E) and x-IAP (F) were lower in SHR vs. WKY (main effect; P < 0.05). Brackets indicate statistical differences. *P < 0.05 for WKY vs. SHR; †P < 0.05 for SED vs. TRD; ^$P < 0.05 vs. all other groups.

Fig. 4.

RT-PCR. Calcineurin A mRNA was significantly increased in SHR-SED (P < 0.05; following a significant interaction effect) and mitigated with training in SHR-TRD. Data are expressed relative to an individual animal from the WKY-SED group to reflect fold change. RQ, group difference. ^$P < 0.05 vs. all other groups.