Effects of Non-selective NO Inhibition on Hypoxia-, Acetylcholine- and Bradykinin-induced Vasoconstriction in Septic Isolated Rat Lungs.
10.4097/kjae.2003.44.6.877
- Author:
Yoon Jeong CHOI
1
;
Choon Hi LEE
;
Seong Deok KIM
Author Information
1. Department of Anesthesiology, Maria Hospital, Korea. yj_choi65@hanmail.net
- Publication Type:Original Article
- Keywords:
Endotoxemia;
hypoxic pulmonary vasoconstriction;
lipopolysaccharide;
nitric oxide synthase inhibitor
- MeSH:
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
- From:Korean Journal of Anesthesiology
2003;44(6):877-885
- CountryRepublic of Korea
- Language:Korean
-
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.
