Combined inhaled nitric oxide and inhaled prostacyclin during experimental chronic pulmonary hypertension.
Inhaled nitric oxide (NO) and inhaled prostacyclin (PGI2) produce selective reductions in pulmonary vascular resistance (PVR) through differing mechanisms. NO decreases PVR via cGMP, and PGI2 produces pulmonary vasodilation via cAMP. As a general pharmacological principle, two drugs that produce similar effects via different mechanisms should have additive or synergistic effects when combined. We designed this study to investigate whether combined inhaled NO and PGI2 therapy results in additive effects during chronic pulmonary hypertension in the rat. Monocrotaline injected 4 wk before study produced pulmonary hypertension in all animals. Inhaled NO (20 parts/million) reversibly and selectively decreased pulmonary artery pressure (Ppa) with a mean reduction of 18%. Four concentrations of PGI2 were administered via inhalation (5, 10, 20, and 80 microg/ml), both alone and combined with inhaled NO. Inhaled PGI2 alone decreased Ppa in a dose-dependent manner with no change in mean systemic arterial pressure. Combined inhaled NO and PGI2 selectively and significantly decreased Ppa more did than either drug alone. The effects were additive at the lower concentrations of PGI2 (5, 10, and 20 microg/ml). The combination of inhaled NO and inhaled PGI2 may be useful in the management of pulmonary hypertension.
Hill
L L
LL
Department of Anesthesia, Stanford University Medical Center, Stanford, California 94305-5123, USA. lhill@leland.stanford.edu
Pearl
R G
RG
D000280:Administration, Inhalation; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002908:Chronic Disease; D004357:Drug Synergism; D011464:Epoprostenol / Q000008:administration & dosage / Q000627:therapeutic use*; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline; D009569:Nitric Oxide / Q000008:administration & dosage / Q000627:therapeutic use*; D011651:Pulmonary Artery / Q000187:drug effects / Q000502:physiology / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
D009569:Nitric Oxide; D016686:Monocrotaline; D011464:Epoprostenol