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% V̇O2peak, 5 d·wk−1, 6 months), while Wistar-Kyoto rats (WKY) (N = 12) served as normotensive controls. LV performance was established in response to supraphysiologic Ca2+ infusion (4 mmol·L−1) alone and concomitant with isoproterenol (ISO) (1 × 10−8 mol·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·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 rats 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 Ser16 and Thr17 residues were positively correlated with LV functional recovery. Regulatory proteins such as the Na+/H+ exchanger, Na+/Ca2+ exchanger, and the L-type Ca2+ 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 a myocardial phenotype that preserved Ca2+ responsiveness during acidosis.
1Department of Kinesiology, 2Cardiovascular Research Center, and 3Department of Physiology, Temple University, Philadelphia, PA
Address for correspondence: Joseph R. Libonati, Ph.D., Department of Kinesiology, Temple University, 122 Pearson Hall, 1800 North Broad Street, Philadelphia, PA 19122; E-mail: firstname.lastname@example.org.
Submitted for publication September 2005.
Accepted for publication December 2005.