Influence of Cellular Energy Metabolism on Contractions of Porcine Carotid Artery Smooth Muscle

Abstract

A number of cellular metabolites, including inorganic phosphate and ADP, have been proposed to regulate the contractions of smooth muscle. Hypothesizing that one of these would have a greater influence than the others, parallel experiments using tissue mechanics and ³¹P-NMR allowed comparison of several metabolic components with the generation of force in porcine carotid artery smooth muscle during long-term contractions. P_i, ADP, ATP, PCr, free energy, pH, and free Mg²⁺ were determined from phosphate spectra during a control-hypoxia-postcontrol sequence generated during K⁺ stimulation by replacement of oxygen with nitrogen using either pyruvate or glucose as substrate. Both pH and free Mg²⁺ were significantly lower in control pyruvate-supplied tissues than in glucose-supplied tissues. Mechanical experiments following the same protocol produced variations in force. The pyruvate series produced the greater range of mechanical and metabolic changes. Linear and logarithmic regression analysis found the order of correlation with force to be highest for P_i, followed by pH, free energy, PCr, ATP, ADP, and free Mg²⁺. The results are consistent with models for the regulation of myosin ATPase by free phosphate inhibition. The results are inconsistent with models of ADP as a regulator of smooth muscle force. Perturbations which alter intracellular phosphate, such as creatine loading, may produce side effects on the contractions of vascular smooth muscle.