Combined therapy with inhaled nitric oxide and intravenous vasodilators during acute and chronic experimental pulmonary hypertension.
Both inhaled nitric oxide (NO) and IV vasodilators decrease pulmonary hypertension, but the effects of combination therapy are unknown. We studied the response to inhaled NO (100 ppm) alone, IV vasodilator alone, and combined therapy during acute (U46619-induced) and chronic (monocrotaline-induced) pulmonary hypertension in the pentobarbital-anesthetized rat. Vasodilator doses were 1.0, 3.2, 10, and 32 microg x kg(-1) x min(-1) sodium nitroprusside (SNP); 50, 100, 150, 200, and 300 microg x kg(-1) x min(-1) adenosine; or 25, 50, 150, 200, and 300 ng x kg(-1) x min(-1) prostacyclin. In the absence of IV vasodilator therapy, inhaled NO decreased mean pulmonary artery pressure without decreasing mean systemic arterial pressure. In both acute and chronic pulmonary hypertension, the addition of inhaled NO to the largest dose of adenosine or prostacyclin, but not of SNP, decreased pulmonary artery pressure. Because inhaled NO and SNP activate guanylyl cyclase and adenosine and prostacyclin activate adenylyl cyclase, the results suggest that adding inhaled NO to a vasodilator not dependent on guanylyl cyclase may produce additional selective pulmonary vasodilation.


CONCLUSIONS
In therapy of pulmonary hypertension, inhaled nitric oxide should produce additional selective pulmonary vasodilation when combined with a vasodilator whose mechanism of action is not dependent on cyclic guanosine 3',5'-monophosphate.
Aranda
M
M
Department of Anesthesia, Stanford University Medical Center, California 94305-5117, USA.
Bradford
K K
KK
Pearl
R G
RG
D000208:Acute Disease; D000241:Adenosine / Q000008:administration & dosage; D000280:Administration, Inhalation; D000818:Animals; D002908:Chronic Disease; D004359:Drug Therapy, Combination; D011464:Epoprostenol / Q000008:administration & dosage; D006976:Hypertension, Pulmonary / Q000188:drug therapy*; D007275:Injections, Intravenous; D008297:Male; D009569:Nitric Oxide / Q000008:administration & dosage*; D009599:Nitroprusside / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D014665:Vasodilator Agents / Q000008:administration & dosage*
D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D011464:Epoprostenol; D000241:Adenosine