Enhanced acidotic myocardial Ca2+ responsiveness with training in hypertension

Purpose: We tested how hypertension- induced compensated hypertrophy, both alone and coupled with exercise training, affects left ventricular (LV) Ca2+ responsiveness during acidosis. Methods: Four-month-old female. spontaneously hypertensive rats (SHR) (N = 23) were assigned to a sedentary (SHR-SED) or treadmill-trained (SHR-TRD) group (60% VO2peak 5 d center dot wk(-1). 6 months). while Wistar-Kyoto rats (WKY) (N = 12) served its normotensive controls. LV performance was established in response to supraphysiologic Ca2+, infusion (4 mmol center dot L-1) alone and concomitant with isoproterenol (ISO) (1 x 10(-8) mol center dot L-1) at pH 7.4 and 6.8. Results: HR. rate-pressure product (RPP), and blood pressure were greater in SHR than in WKY (P < 0.05). HR and RPP were attenuated with training. Heart weight and LV anterior wall thickness (diastole) were increased in SHR relative to WKY (P < 0.05) and augmented with training. ISO + 4 mmol center dot L-1 [Ca2+](o) resulted in similar LV performance at pH 7.4. At pH 6.8. LV developed pressure was greater in both SHR groups (P < 0.05) Versus WKY and a twofold increase in the [Ca2+](o) rescued LV performance to the greatest extent in SHR-TRD. During acidosis, the added stimulus of ISO coupled with elevated [Ca2+](o) improved WKY LV performance to near baseline (P < 0.05). Neither elevated [Ca2+](o) nor ISO was effective in rescuing LV performance in SHR-SED during acidosis. Phospholamban phosphorylation at Ser(16) and Thr(17) residues were positively correlated with LV functional recovery. Regulatory proteins Such as the Na+/H+ exchanger. Na+/Ca2+ exchanger. and the L-type C,121 channel were not correlated with LV function. Conclusion: Myocardial tolerance to acidosis is improved during the adaptive phase of compensatory hypertrophy. Furthermore, exercise training in SHR induced it myocardial phenotype that preserved Ca2+ responsiveness during acidosis.