The effects of metabolic inhibition and acidification on force production in the rat uterus.

The effects of hypoxia and intracellular acidification were examined on the mechanical properties of the non-pregnant and pregnant rat uterus. Isolated uteri were investigated during control conditions and in the presence of cyanide, to simulate hypoxia or the salts of weak acids and bases to change intracellular pH at constant external pH (pH 7.4). Both spontaneous contractions and high-K contractures (i.e. fully activated preparations) were investigated at 37 degrees C. In control solutions both pregnant and non-pregnant uteri were spontaneously active and gave a contracture when bathed with a high-K+ solution. When oxidative phosphorylation was inhibited by cyanide, spontaneous contractions were either greatly reduced or abolished. The effects on spontaneous contractions were more pronounced in the non-pregnant than the pregnant uterus. If high-K solution was added after cyanide had abolished spontaneous contractions, then a small amount of force was produced. High-K-induced contractures were not maintained in the presence of cyanide and quickly fell to baseline levels in both pregnant and non-pregnant uteri. All the effects of cyanide were fully reversible. When only intracellular pH was changed by adding weak acids (50 mM-butyrate or propionate), spontaneous contractions were greatly diminished or abolished in both pregnant and non-pregnant uteri. However, the application of weak acids had no effect upon the KCl-induced contractures in both pregnant and non-pregnant uteri. The effects of cyanide on the uterus include both an acidification and changes in metabolites, e.g. a fall in [ATP]. To investigate the changes in metabolites without a change in pHi, cyanide was applied with the weak base trimethylamine (40-50 mM). 31P Nuclear magnetic resonance spectroscopy was used to show that the alkalinization which occurs with trimethylamine alone abolished the acidification ordinarily associated with cyanide. Spontaneous and high-K-induced contractions were greatly reduced or abolished, i.e. the result was the same as with cyanide alone. This occurred in both pregnant and non-pregnant uteri. It is concluded that spontaneous force production is affected by both changes in metabolites (e.g. decreased [ATP] and increased inorganic phosphate) and pHi, and that both can depress activation of the uterus. Only the changes in metabolites can depress force production in fully activated preparation. The greater effect on force in the non-pregnant uterus compared to the pregnant uterus may be due to the lower initial levels of [ATP] and the greater fall in ATP seen in non-pregnant compared to pregnant uterus, and gestational changes in metabolism.(ABSTRACT TRUNCATED AT 400 WORDS)