Skeletal Muscle Signaling and the Heart Rate and Blood Pressure Response to Exercise

Abstract

Abstract-Endurance training lowers heart rate and blood pressure responses to exercise, but the mechanisms and consequences remain unclear. To determine the role of skeletal muscle for the cardioventilatory response to exercise, 8 healthy young men were studied before and after 5 weeks of 1-legged knee-extensor training and 2 weeks of deconditioning of the other leg (leg cast). Hemodynamics and muscle interstitial nucleotides were determined during exercise with the (1) deconditioned leg, (2) trained leg, and (3) trained leg with atrial pacing to the heart rate obtained with the deconditioned leg. Heart rate was ≈15 bpm lower during exercise with the trained leg (P<0.05), but stroke volume was higher (P<0.05) and cardiac output was similar. Arterial and central venous pressures, rate-pressure product, and ventilation were lower during exercise with the trained leg (P<0.05), whereas pulmonary capillary wedge pressure was similar. When heart rate was controlled by atrial pacing, stroke volume decreased (P<0.05), but cardiac output, peripheral blood flow, arterial pressures, and pulmonary capillary wedge pressure remained unchanged. ] were lower and interstitial [ATP] and pH were higher in the trained leg (P<0.05). The lower cardioventilatory response to exercise with the trained leg is partly coupled to a reduced signaling from skeletal muscle likely mediated by K + , lactate, or pH, whereas the lower cardiac afterload increases stroke volume. These results demonstrate that skeletal muscle training reduces the cardioventilatory response to exercise without compromising O 2 delivery, and it can therefore be used to reduce the load on the heart during physical activity.

Cardiovascular Adaptations to Exercise Training

“…During muscle contractions, the concentration of ATP increases in the extracellular space in proportion to the intensity of contraction (176,260) and interstitial ATP has been shown to induce vasodilatation in skeletal muscle (313). The concentration of skeletal muscle interstitial ATP during exercise is reduced with immobilization (296) and increased in lifelong physically active men (295). In agreement with these observations, a close coupling also exist between the concentration of interstitial ATP and the degree of functional sympatholysis (312).…”

“…In addition, some evidence has been provided for that increases in heart volume lowers intrinsic heart rate (224,258). The increase in stroke volume during exercise at a given absolute workload in the trained state is a result of an increase in blood volume, an augmented left ventricular end-diastolic volume, and cardiac preload (198,236) as well as a lower cardiac afterload (arterial pressure) (132,296). Notably, evidence suggests that cardiac output during exercise is regulated by peripheral oxygen demand (16,156) and that this regulation is independent of training status (296).…”

“…Exercise training leads to a reduction in blood pressure and sympathetic drive during acute submaximal exercise performed at the same absolute intensity when muscles of the lower limb are recruited (75,110,296,346,457) (Fig. 2).…”

“…As previously described, heart rate is lower during exercise engaging a trained muscle group. Despite this effect on heart rate, stroke volume still remains higher in the trained state which primarily is the result of the lower arterial blood pressure and hence cardiac afterload (296).…”

Exercise Training Reverses Skeletal Muscle Atrophy in an Experimental Model of VCP Disease

“…Exercise physiology has also been reported to enhance muscle mitochondrial biogenesis and protection for mice with mitochondrial myopathies [26], [27]. Chronic aerobic exercise has been shown to stimulate the 5′-AMP-activated protein kinase (AMPK) activity [28]–[30]. Similarly, the beneficial effects of endurance training have been demonstrated in the transgenic nemaline mouse model of the extensor digitorum longus (EDL) muscle, revealing a novel myofiber repair mechanism [31].…”