Fig. 6.

Schematic of potential central and peripheral cardiovascular impairments that could compromise steady-state convective and diffusive oxygen delivery to the contracting skeletal muscle myocyte, thereby contributing to exercise intolerance. The vessel shows capillary (left side) and upstream arteriolar (right side) levels of the vascular tree. Sympathetic restraint of exercising skeletal muscle vasodilation could be enhanced due to 1) reduced CBR inhibition of sympathetic neural outflow to compensate for inadequate CO and maintain arterial blood pressure, 2) CSAR stimulation in a diabetic heart, and/or 3) MMR activation. Impaired functional sympatholysis would reduce blunting of sympathetic restraint. The vasodilatory response to increased muscle metabolic demand for oxygen in contracting skeletal muscle could be compromised due to 1) endothelial and/or 2) smooth muscle dysfunction, and/or 3) impaired RBC release of ATP and/or nitric oxide (NO) with hemoglobin (Hb) deoxygenation. Diffusive flux of oxygen could be compromised by increased Hb affinity for O₂ and/or structural and functional capillary rarefaction. CBR, carotid baroreflex; CO, cardiac output; CSAR, cardiac sympathetic afferent reflex; MMR, muscle metaboreflex.