The effect of sildenafil on pulmonary embolism-induced oxidative stress and pulmonary hypertension.
Acute pulmonary embolism (APE) is a major cause of pulmonary hypertension and death. We examined the effects of sildenafil on the hemodynamic changes caused by APE in anesthetized dogs. Sham-operated dogs (n = 3) received only saline. APE was induced by stepwise IV injections of 300 mum microspheres in amounts adjusted to increase mean pulmonary artery pressures by 20 mm Hg. Hemodynamic evaluation was performed at baseline, after APE was induced, and then after sildenafil 0.25 mg/kg (n = 8), or sildenafil 1 mg/kg + 0.3 mg . kg(-1) . h(-1) (n = 8) or saline (n = 9) infusions were started. Similar experiments were conducted to examine the effects of sildenafil in rat isolated perfused lung preparation. Plasma thiobarbituric acid reactive species were also determined in both studies to measure oxidative stress. Both doses of sildenafil reduced mean pulmonary artery pressures in dogs by approximately 8 to 16 mm Hg (both P < 0.05) and attenuated the increase in oxidative stress after APE. Mean arterial blood pressure remained unaltered after both doses of sildenafil. Sildenafil produced similar effects after APE in rat isolated perfused lung preparation. These findings indicate that IV sildenafil can selectively attenuate the increases in mean pulmonary artery pressures after APE, possibly through antioxidant mechanisms.
Department of Pharmacology, Faculty of Medicine of Ribeirao Preto, University of Sao Paulo, Av. Bandeirantes, 3900, 14049-900 Ribeirao Preto, Sao Paulo, Brazil.
Carlos A
CA
Dias-Junior
Debora C
DC
Souza-Costa
Talita
T
Zerbini
Joao B T
JB
da Rocha
Raquel F
RF
Gerlach
Jose E
JE
Tanus-Santos
D000208:Acute Disease; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006976:Hypertension, Pulmonary / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D018384:Oxidative Stress / Q000187:drug effects*; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D010879:Piperazines / Q000494:pharmacology*; D011651:Pulmonary Artery / Q000502:physiology; D011655:Pulmonary Embolism / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D011687:Purines; D051381:Rats; D017208:Rats, Wistar; D000068677:Sildenafil Citrate; D013450:Sulfones; D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D010879:Piperazines; D011687:Purines; D013450:Sulfones; D017392:Thiobarbituric Acid Reactive Substances; D014665:Vasodilator Agents; D008315:Malondialdehyde; D000068677:Sildenafil Citrate