Graded effects of oxygen and respiratory inhibitors on cell metabolism and spontaneous contractions in smooth muscle of the rat portal vein

Abstract

The basis for the hypoxic relaxation of spontaneous activity in the rat portal vein was investigated by comparing responses to oxygen and the respiratory chain inhibitors amobarbital and cyanide. With the inhibitors, O2 consumption (FO2) is uniformly decreased throughout the cell mass, and thus O2 gradients in the tissue are avoided. Hence the effects are not to be attributed to all-or-none inhibition in anoxic regions, a possibility that might complicate the interpretation of responses to hypoxia. With stepwise reduction in PO2 (96 to o% in N2 + 4% CO2) or increasing concentration of inhibitor (o-5 mmol), FO2 decreased with a concomitant reduction in mean contractile activity (P) and increase in lactate production (FLA). The calculated ATP production (FATP) was linearly related to P for P greater than 10% of the control value in 96% O2, with the same slope for hypoxia and both inhibitors. In this range the reduced FATP with P can largely be attributed to decreased metabolic demand of contraction, as evident from a comparison with the responses to hypoxia of portal veins relaxed in nominally Ca2+-free medium. With reduced PO2 or increased amobarbital concentration the tissue content of phosphocreatine decreased, whereas ATP remained constant for P greater than 10% of control. Similar responses to hypoxia and respiratory inhibition demonstrate graded effects on metabolism and contractility in the vascular smooth muscle cells, correlating with reported vasodilatory effects of these interventions in vivo.