Diamide Inhibits Pulmonary Vasoconstriction Induced by Hypoxia or Prostaglandin F_2α

Diamide oxidizes glutathione and other cellular sulfhydryl groups. It decreases calcium ATPase activity and alters mitochondrial calcium flux, probably as a result of the sulfhydryl oxidation. We examined the effect of diamide (5 mg/kg, iv) on pulmonary vascular reactivity in 12 anesthetized dogs. Diamide reversed the pulmonary vasoconstriction caused by hypoxia in seven dogs (control ΔPVR + 2.5 ± 0.6 mm Hg/liter/min; postdiamide ΔPVR −0.1 ± 0.4 mm Hg/liter/min; P < 0.01). The pulmonary pressor response to prostaglandin F_2α (5 μg/kg/ min, iv) was also reduced (control ΔPVR + 3.8 ± 0.5 mm Hg/liter/min; postdiamide ΔPVR + 1.1 ± 0.7 mm Hg/liter/min; P < 0.01). However, in a further five dogs, diamide had only a small effect on the pulmonary vasoconstriction caused by angiotensin II, while the pressor response to hypoxia was again inhibited. The mechanism by which diamide reverses pulmonary vasoconstriction is not certain but the effect is rapid, consistent, and reversible. Because the intravenous infusion of diamide does not produce systemic hypotension, during its period of action on the pulmonary vasculature, unlike the drugs currently available for the clinical treatment of pulmonary hypertension, further studies of its mechanism of action are indicated.