Hypoxia Impairs Endothelial Function in HAPEs
Raktažodžiai
Santrauka
apibūdinimas
Rationale: High-altitude pulmonary edema (HAPE) is characterized by excessive pulmonary vasoconstriction and is associated with decreased concentrations of nitric oxide (NO) in the lung. Objectives: We hypothesized that individuals susceptible to HAPE (HAPE-S) would also have dysfunction of the vascular NO vasodilator pathway during hypoxia in the systemic vasculature. Methods: During normoxia (FI(O(2)) = 0.21) and 4 hours of normobaric hypoxia (FI(O(2)) = 0.12, corresponding to an altitude of 4,500 m above sea level) endothelium-dependent and endothelium-independent vasodilator responses to intraarterial infusion of acetylcholine (ACh) and sodium nitroprusside, respectively, were measured by forearm venous occlusion plethysmography in nine HAPE-S subjects and in nine HAPE-resistant control subjects. Main Results: Pulmonary artery systolic pressure increased from 22 +/- 3 to 33 +/- 6 mm Hg (p < 0.001) during hypoxia in control subjects, and from 25 +/- 4 to 50 +/- 9 mm Hg in HAPE-S subjects (p < 0.001). Despite similar responses during normoxia in both groups, ACh-induced changes in forearm blood flow markedly decreased during hypoxia in HAPE-S subjects (p = 0.01) but not in control subjects. The attenuated vascular response to ACh infusion during hypoxia inversely correlated with increased pulmonary artery systolic pressure (p = 0.04) and decreased plasma nitrite correlated with attenuated ACh-induced vasodilation in HAPE-S subjects (p = 0.02). Conclusions: Hypoxia markedly impairs vascular endothelial function in the systemic circulation in HAPE-S subjects due to a decreased bioavailability of NO. Impairment of the NO pathway could contribute to the enhanced hypoxic pulmonary vasoconstriction that is central to the pathogenesis of HAPE.
Datos
Paskutinį kartą patikrinta: | 05/31/2005 |
Pirmasis pateikimas: | 09/09/2005 |
Numatytas registravimas pateiktas: | 09/09/2005 |
Pirmas paskelbtas: | 09/14/2005 |
Paskutinis atnaujinimas pateiktas: | 09/09/2005 |
Paskutinis atnaujinimas paskelbtas: | 09/14/2005 |
Būklė ar liga
Intervencija / gydymas
Procedure: Hypoxia
Fazė
Tinkamumo kriterijai
Amžius, tinkami studijuoti | 18 Years Į 18 Years |
Tinkamos studijoms lytys | All |
Priima sveikus savanorius | Taip |
Kriterijai | Inclusion Criteria: Healthy, male volunteers, age: 18-55 - Able and willing to give written informed consent Exclusion Criteria: - Known condition causing endothelial dysfunction (e.g. diabetes, hyperlipidaemia, arterial hypertension, smoking, hyperhomocysteinaemia) - Regular medication and/or treatment with drugs within the last 4 weeks (exclusion has to be decided in each case) - Acute or chronic illness - Participation in clinical trial/blood donation within 2 month before the study - Nicotine, drug and/or alcohol abuse. |