Oxidants: a new group of pulmonary vasodilators

2-Butanone peroxide and t-butyl hydroperoxide cause the oxidation of glutathione and other cellular sulfhydryl groups. We examined the effect of these agents on pulmonary vascular reactivity in 13 anesthetized dogs, 2-Butanone peroxide decreased the pulmonary vascular resistance attained after 15 min of hypoxia (F10₂ 10%) in seven dogs from 6.3 ± 0.4 to 3.4 ± 0.3 mmHg x 1^-1 x min^-1 (p<0.01) while leaving systemic arterial pressure unchanged. t-Butyl hydroperoxide decreased the 15 min hypoxic pulmonary vascular resistance in six dogs from 6.3 ± 0.9 to 3.7 ± 0.6 mmHg x 1^-1 x min^-1 (p<0.01), but systemic arterial pressure also fell from 168 ± 9 to 109 ± 16 mmHg (p<0.01). The mechanism by which these agents cause pulmonary vasodilatation is not certain but might involve the oxidation of sulfhydryl groups in enzymes or membranes. Because 2-butanone peroxide given intravenously did not produce systemic hypotension, unlike t-butyl hydroperoxide and the drugs currently available for the clinical treatment of pulmonary hypertension, further studies of its mechanism of selective action are indicated.