title: Nitric oxide plays a minimal role in hypoxic pulmonary vasoconstriction in isolated rat lungs.
abstract: The goal of this study was to elucidate the importance of nitric oxide production during hypoxic pulmonary vasoconstriction (HPV). One group of Sprague Dawley rats received an ip injection of saline (controls), while a second group received an ip injection of Escherichia coli lipopolysacharides (LPS-treated) to render them septic. Three hours later, the animals were anesthetized and prepared for the isolated lung experiment. The lungs were ventilated and perfused with diluted autologous blood (Hct 23%) at constant flow rate while monitoring pulmonary arterial pressure (Pa). Nitric oxide production from the lungs was monitored by measuring its concentration in the mixed exhaled gas (NOe) offline. NOe in the isolated lungs was 2 ppb in controls and 90 ppb in the LPS treated lungs. Hypoxia caused Pa to rise from 10 to 17 mmHg in control lungs, and from 10 to 27 mmHg in the LPS treated lungs. NO production was then manipulated to determine if it affects HPV. NOe was increased by adding L-arginine to the blood, and was blocked by adding nitro-L-arginine (LNA). L-Arginine had minimal effect on NOe in control lungs, but increased NOe in LPS treated lungs, and yet HPV was similar in the 2 groups. Despite inhibition of NO synthesis with nitro-L-arginine (LNA), HPV was potentiated equally in control and in LPS treated lungs (Pa rose by 23 mmHg). Thus NO production did not affect the difference in HPV between control and LPS treated lungs. The results suggest that NO does not plays a primary role in HPV.
authors.affiliation: Sleep Apnea Treatment Center, Phoenix, AZ, United States. Electronic address: salthakim@yahoo.com.
authors.forename: T S
authors.initials: TS
authors.lastname: Hakim
authors.forename: A
authors.initials: A
authors.lastname: Pedoto
authors.forename: D
authors.initials: D
authors.lastname: Mangar
authors.forename: E M
authors.initials: EM
authors.lastname: Camporesi
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D000860:Hypoxia / Q000378:metabolism*; D008070:Lipopolysaccharides / Q000633:toxicity; D008168:Lung / Q000378:metabolism*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D011652:Pulmonary Circulation / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000139:chemically induced / Q000378:metabolism; D014661:Vasoconstriction / Q000502:physiology*
chemical_list: D008070:Lipopolysaccharides; D009569:Nitric Oxide
keywords: Hypoxia; Hypoxic vasoconstriction; Isolated lung; Lung; Nitric oxide; Pulmonary vascular resistance; Temperature; l-Arginine