Abstract 389

We demonstrated that the metabolic inhibitors DNP and AMA, inhibit ATP release and pulmonary vasodilation caused by birth related stimuli in fetal lambs. DNP and AMA cause inhibition of oxidative phosphorylation by different mechanisms. DNP is an uncoupler of oxidative phosphorylation and AMA inhibits cytochrome electron transport. We investigated whether DNP and AMA also have different effects on vascular responses of fetal pulmonary circulation to known endothelium dependent and independent vasodilators. Studies were done in 14 fetal lambs instrumented at 124 d gestation to measure vascular pressures and pulmonary blood flow. Baseline studies were done with infusion of acetylcholine (ACH), an endothelium dependent vasodilator and SNAP, a nitric oxide (NO) donor and an independent vasodilator. Then fetal lambs were assigned to pretreatment with either 1 mg DNP or 0.5 mg AMA and studies were repeated. Data are shown as mean ± 1SD. * indicates p < 0.05 from BL and # from control data. Doses of ACH and SNAP are in µg. (Table) The vasodilation caused by ACH and SNAP were not altered by DNP. However, AMA attenuated the vasodilation caused by ACH and SNAP. These differences indicate that AMA may have non specific effects on vasoreactivity unrelated to its effect on oxidative phosphorylation or that different phases of cellular respiration may be involved in NO dependent vasodilation. DNP may be a better agent to evaluate the role of metabolic effects of 02 in mediating its pulmonary vasodilator effects.

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