Korean J Anesthesiol.  2003 Jun;44(6):877-885. 10.4097/kjae.2003.44.6.877.

Effects of Non-selective NO Inhibition on Hypoxia-, Acetylcholine- and Bradykinin-induced Vasoconstriction in Septic Isolated Rat Lungs

• Choi YJ
• Lee CH
• Kim SD

• KMID: 2239965
• DOI: http://doi.org/10.4097/kjae.2003.44.6.877

Abstract

BACKGROUND: Endotoxin stimulates nitric oxide synthase (NOS) and the free radical nitric oxide (NO) is produced by NOS, which vasodilates the smooth muscle of pulmonary vessels. Otherwise, endotoxemia stimulates the release of cyclooxygenase (COX) products, which may modify hypoxic pulmonary vasoconstriction (HPV). We also observed the effect of nonselective NOS inhibition by NG-nitro-L-arginine methyl ester (L-NAME) on receptor-mediated acetylcholine (Ach)/bradykinin (BK) induced vasoconstriction and receptor independent HPV in E.coli lipopolysaccharide (LPS) induced septic isolated rat lungs.
METHODS
Four hours before surgical instrumentation for lung isolation, we administered saline (1 ml) to the control group (n = 15), E.coli LPS (20 mg/kg) to the LPS group (n = 14) and LPS (30 mg/kg) the nitric oxide synthase inhibitor, L-NAME (15 mg/kg) to the LPS + L-NAME group (n = 14), intraperitoneally. In 43 isolated rat lungs perfused with physiologic salt-albumin- blood mixture, angiotensin II 0.2 microgram was injected into the perfusion circuit, to confirm pulmonary vascular reactivity in each isolated lung. HPV responses were induced by three hypoxic challenges for 5 minutes separated by 5 minutes of ventilation with a normoxic gas mixture. We observed the pulmonary arterial pressure at each challenge, ten minutes after the last HPV, 0.01, 0.1, 1.0 microgram of Ach and 1, 3, 10 microgram of BK were injected. PAP and static lung compliance were measured.
RESULTS
The baseline pulmonary artery pressure in the LPS group higher than in the controls and HPV in the LPS group was changed compared to the controls but in the LPS + L-NAME it was higher than in the controls. The administration of Ach 0.1, 1.0 microgram and BK 3, 10 microgram causedpulmonary vasoconstriction and the vasoconstrictions of BK were dosage-dependent. Lung stiffness in the LPS and LPS + L-NAME groups were higher than those of the controls.
CONCLUSIONS
Vascular constriction of pulmonary vessels and increased lung stiffness by Ach and BK might be the result of the endothelial injury. But pulmonary vasoconstriction and stiffness by Ach and BK were similar in the LPS and LPS + L-NAME groups, showing that factors other rather than excessive NO production might be involved in endothelial injury.

Keyword

Endotoxemia; hypoxic pulmonary vasoconstriction; lipopolysaccharide; nitric oxide synthase inhibitor

MeSH Terms

Acetylcholine
Angiotensin II
Animals
Arterial Pressure
Constriction
Endotoxemia
Lung Compliance
Lung*
Muscle, Smooth
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Perfusion
Prostaglandin-Endoperoxide Synthases
Pulmonary Artery
Rats*
Surgical Instruments
Vasoconstriction*
Ventilation
Acetylcholine
Angiotensin II
NG-Nitroarginine Methyl Ester
Nitric Oxide
Nitric Oxide Synthase
Prostaglandin-Endoperoxide Synthases