Combined inhaled nitric oxide and inhaled prostacyclin during experimental chronic pulmonary hypertension

• Published in: Journal of applied physiology (1985) Vol. 86; no. 4; pp. 1160 - 1164
• Main Authors: Hill, Laureen L, Pearl, Ronald G
• Format: Journal Article
• Language: English
• Published: Bethesda, MD Am Physiological Soc 01-04-1999; American Physiological Society
• Subjects: Administration, Inhalation; Animals; Biological and medical sciences; Blood Pressure - drug effects; Chronic Disease; Drug Synergism; Drug therapy; Epoprostenol - administration & dosage; Epoprostenol - therapeutic use; Hypertension; Hypertension, Pulmonary - chemically induced; Hypertension, Pulmonary - drug therapy; Hypertension, Pulmonary - physiopathology; Lungs; Male; Medical sciences; Monocrotaline; Nitric Oxide - administration & dosage; Nitric Oxide - therapeutic use; Pharmacology. Drug treatments; Pulmonary Artery - drug effects; Pulmonary Artery - physiology; Pulmonary Artery - physiopathology; Rats; Rats, Sprague-Dawley; Respiratory system; Rodents; Vasodilation - drug effects; Vasodilation - physiology; Prostaglandin I2; Rat; Respiratory disease; Rodentia; Cardiovascular disease; Synergism; Pulmonary hypertension; Inhalation; Resistance; Vertebrata; Chemotherapy; Experimental disease; Mammalia; Treatment; Pulmonary vessel; Animal; Nitric oxide; Combined treatment
• ISSN: 8750-7587; 1522-1601
• DOI: 10.1152/jappl.1999.86.4.1160

Department of Anesthesia, Stanford University Medical Center,
Stanford, California 94305
Inhaled nitric
oxide (NO) and inhaled prostacyclin
(PGI 2 ) produce selective
reductions in pulmonary vascular resistance (PVR) through differing
mechanisms. NO decreases PVR via cGMP, and
PGI 2 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
PGI 2 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 PGI 2
were administered via inhalation (5, 10, 20, and 80 µg/ml), both
alone and combined with inhaled NO. Inhaled
PGI 2 alone decreased Ppa in a
dose-dependent manner with no change in mean systemic arterial
pressure. Combined inhaled NO and
PGI 2 selectively and significantly
decreased Ppa more did than either drug alone. The effects were
additive at the lower concentrations of
PGI 2 (5,   10, and 20 µg/ml). The combination of inhaled NO and inhaled
PGI 2 may be useful in the
management of pulmonary hypertension.
pulmonary vascular resistance; monocrotaline; adenosine
3',5' cyclic monophosphate; guanosine 3',5'
cyclic monophosphate; rat; vasodilator