Role of cGMP Signaling for Training-induced Vascular and Skeletal Muscle Adaptations in Young and Older Humans

Aging is associated with impaired blood flow regulation; however, the mechanisms underlying this impairment and to what extent a period of exercise training can improve the matching between O2 delivery and utilization remain unclear. Eight young and 6 older (24 ± 1 vs. 74 ±2 years) healthy sedentary men participated in the study. We examined the vascular response to femoral arterial infusion of the vasoactive compound ATP and the effect of inhibiting the main enzyme involved in cGMP degradation, phosphodiesterase 5 (PDE5), on hemodynamics and O2 uptake in contracting skeletal muscle before and after 10 weeks of aerobic high intensity training. Catheters were placed in the femoral artery and vein of both legs. A microdialysis probe was inserted into one of the venous catheters to allow for measurements of plasma ATP concentrations. Measurements of blood flow, intra-arterial and -venous blood pressure, and arterial and venous O2 content were performed during ATP infusion and knee-extensor exercise. As post-intervention testing is currently being conducted, only data from pre-intervention testing is presented in is this abstract.

At baseline, the ATP-induced change in leg vascular conductance was lower in the older group (P<0.05). During sub maximal knee-extensor exercise in the control setting, O2 uptake tended to be lower (−14%, P=0.093) in the older subjects compared to young subjects. After intake of the highly selective PDE5 inhibitor sildenafil, blood flow, leg vascular conductance and O2 uptake were higher (P<0.05) in the older group during knee-extensor exercise whereas no changes were observed in the young group. These results indicate an insufficient oxygen delivery to the contracting skeletal muscle of aged individuals as a result of reduced cGMP signaling. Data from post-intervention testing will provide insight as to whether exercise training can improve the matching of O2 delivery and utilization via improved cGMP signaling in the older subjects. Also, it is thought that ATP released from red blood cells and the endothelium play a role in blood flow regulation, and data from post-intervention testing will elucidate if a period of exercise training increases ATP sensitivity and/or venous plasma ATP concentrations during exercise.