Myocardial Na+/H+ Exchanger (NHE) Content is Decreased by Exercise Training

Abstract

The sarcolemmal NHE extrudes an intracellular proton in exchange for an extracellular sodium. Skeletal muscle NHE content increases in response to relatively intense exercise training and thereby helps these cells tolerate the stress of an exercise-induced acid load. Measurements of mRNA content suggest that exercise training also elevates NHE in the heart. However, mRNA expression does not always correspond to expression of its protein. An increase in NHE in the heart can be considered to be maladaptive as it can cause damage in response to certain stresses, including ischemia-reperfusion (I-R). During I-R, increased NHE activity results in high intracellular Na+ accumulation, which leads to an increase in intracellular Ca2+ via the Na+/Ca2+ exchanger. The Ca2+ overload then causes contractile dysfunction and cell death. PURPOSE: To determine whether myocardial NHE protein expression is altered by exercise training. METHODS: Adult female Sprague-Dawley rats were divided into sedentary (S, N=8) and exercised (E, N=8) groups. E participated in a 5-week exercise program consisting of running on a treadmill 5 days/week up a 6° incline. Duration and intensity of exercise were gradually increased until the animals were running for 1 hr at 30 meters/min. The exercise room was maintained at 8°C. Twenty-four hrs after the last exercise bout, hearts were weighed and connected to an isolated perfused working heart apparatus for evaluation of cardiac functional performance. Ventricular tissue was homogenized, heart protein measured by Biuret method, and NHE determined by Western blotting. Cytochrome oxidase (Cytox) activity in plantaris was determined as a marker of mitochondria content and to verify training status. Data were analyzed using a two-tailed t-test with P<0.05 as the limit for statistical significance. RESULTS: E increased Cytox 92% in plantaris (P<0.05). E also increased (P<0.05) heart weight by 7.1%, heart weight/body weight by 7.2%, cardiac output (CO) by 21.1%, external cardiac work (CO x systolic pressure) by 35.8%. NHE content was 38% lower in E than in S (P<0.05). CONCLUSION: Exercise training at an intensity that results in cardiac hypertrophy and improved performance is accompanied by decreased NHE content in heart. This decrease in NHE could contribute to exercise-induced cardioprotection.