Diamide inhibits pulmonary vasoconstriction induced by hypoxia or prostaglandin F2 alpha.
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 delta PVR + 2.5 +/- 0.6 mm Hg/liter/min; postdiamide delta PVR - 0.1 +/- 0.4 mm Hg/liter/min; P less than 0.01). The pulmonary pressor response to prostaglandin F2 alpha (5 micrograms/kg/min, iv) was also reduced (control delta PVR + 3.8 +/- 0.5 mm Hg/liter/min; postdiamide delta PVR + 1.1 +/- 0.7 mm Hg/liter/min; P less than 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.
D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001391:Azo Compounds / Q000494:pharmacology*; D003864:Depression, Chemical; D003958:Diamide / Q000494:pharmacology*; D015237:Dinoprost; D004285:Dogs; D005260:Female; D000860:Hypoxia / Q000503:physiopathology*; D008168:Lung / Q000098:blood supply*; D008297:Male; D010100:Oxygen / Q000502:physiology; D011460:Prostaglandins F / Q000008:administration & dosage; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects*
D001391:Azo Compounds; D011460:Prostaglandins F; D003958:Diamide; D000804:Angiotensin II; D015237:Dinoprost; D010100:Oxygen