A number of cellular metabolites, including inorganic phosphate and ADP, ha
ve been proposed to regulate the contractions of smooth muscle. Hypothesizi
ng that one of these would have a greater influence than the others, parall
el experiments using tissue mechanics and P-31-NMR allowed comparison of se
veral metabolic components with the generation of force in porcine carotid
artery smooth muscle during long-term contractions. P-i, ADP, ATP, PCr, fre
e energy, pH, and free Mg2+ were determined from phosphate spectra during a
control-hypoxia-postcontrol sequence generated during K+ stimulation by re
placement of oxygen with nitrogen using either pyruvate or glucose as subst
rate. Both pH and free Mg2+ were significantly lower in control pyruvate-su
pplied tissues than in glucose-supplied tissues. Mechanical experiments fol
lowing 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 t
o 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 AT
Pase by free phosphate inhibition. The results are inconsistent with models
of ADP as a regulator of smooth muscle force. Perturbations which alter in
tracellular phosphate, such as creatine loading, may produce side effects o
n the contractions of vascular smooth muscle. Copyright (C) 2000 S. Karger
AG, Basel.