Integrated myogenic and metabolic control of vascular tone in skeletal muscle during autoregulation of blood flow.

The hypothesis that autoregulation of blood flow in cat skeletal muscle is due to metabolic factors related to blood flow that interact with force-sensitive myogenic mechanisms is tested by means of a mathematical model. The vascular bed is assumed to consist of the reactive series-coupled proximal arterial and microvascular sections and the passive large vein section. Myogenic mechanisms are described by a slowly adapting force-receptor that determines the activation level of smooth muscle. The contractile machinery is represented by our recently developed mathematical model of smooth muscle mechanics. The metabolic control is described by the vasodilator theory whereby changes in the interstitial concentration of a dilator substance(s) alter the excitation-contraction coupling by shifting the [Ca2+]-force relationship. Experimental results indicate that the model correctly simulates vascular resistance responses to a variety of pressure stimuli, as well as autoregulation of blood flow and capillary pressure. Our results show that autoregulation of blood flow requires myogenic mechanisms which act synergistically with metabolic factors related to blood flow. It is also shown that the autoregulation of capillary pressure can be attributed to passive pressure-induced changes of postcapillary resistance, and that in autoregulation of blood flow the concentration of the mediating vasodilator metabolite(s) is a controlled variable being kept virtually constant in the range where blood flow is autoregulated.