Inhibition of nitric oxide synthesis improves arterial oxygenation in ethchlorvynol-induced acute lung injury in dogs.

Abstract

In both humans and in experimental animals, acute lung injury (ALI) is characterized by the development of pulmonary edema and arterial hypoxemia. It has been reported that the hypoxemia of ALI is related to the failure of those mechanisms that result in the diversion of blood flow away from hypoxic (edematous) lung units to those that are well oxygenated. One such mechanism is hypoxic pulmonary vasoconstriction (HPV). In the pulmonary circulation, endogenous nitric oxide (NO) has been shown to oppose HPV and, thereby, to support blood flow to hypoxic alveoli. In the present work we investigated the hypothesis that, in ALI, endogenous NO, by virtue of its ability to oppose HPV, supports blood flow to hypoxic lung units resulting in increases in venous admixture (Qva/Qt) and decreases in arterial oxygen tension (PaO2). In anesthetized and mechanically ventilated dogs, the intravenous administration of ethchlorvynol (ECV, 15 mg/kg) resulted in an increase in extravascular lung water (EVLW) of 10 +/- 1 ml/kg body wt (p < 0.001) as well as a 120 +/- 45% increase in Qva/Qt (p < 0.01) and a 23 +/- 5% decrease in PaO2 (p < 0.01) (n = 3). L-NAME (1 mg/kg iv, followed by 5 mg/kg/h, iv), administrated 60 min after ethchlorvynol (ECV), prevented entirely the ECV-induced increase in Qva/Qt and fall in PaO2 with minimal effect on EVLW (n = 3). We conclude that, in this model of ALI, endogenous NO is present in the lung and acts to support blood flow to poorly oxygenated lung units resulting, thereby, in reductions in PaO2.

• Authors: R S Sprague, A H Stephenson, L McMurdo, A J Lonigro
• Journal: Polish journal of pharmacology (Pol J Pharmacol) 1995 Sep-Oct Vol. 47 Issue 5 Pg. 473-8 ISSN: 1230-6002 [Print] Poland
• PMID: 8868143 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.)

Chemical References

• Enzyme Inhibitors
• Nitric Oxide
• Ethchlorvynol
• Nitric Oxide Synthase
• Oxygen
• NG-Nitroarginine Methyl Ester

Topics

• Animals
• Blood Gas Analysis
• Dogs
• Enzyme Inhibitors (therapeutic use)
• Ethchlorvynol
• Extravascular Lung Water (drug effects)
• Hemodynamics (drug effects)
• Hypoxia (physiopathology)
• Lung Diseases (blood, chemically induced, metabolism)
• Male
• NG-Nitroarginine Methyl Ester (therapeutic use)
• Nitric Oxide (biosynthesis)
• Nitric Oxide Synthase (antagonists & inhibitors)
• Oxygen (blood)