ENDOGENOUS NITRIC OXIDE AND CARBON MONOXIDE
SYSTEMS IN THE DEVELOPMENT OF HYPOXIC PULMONARY HYPERTENSION
Du Junbao, Qi JG, Shi Y, Tian
H, Guo ZL, Zhao B, Cui YN, Zhou B, Li WZ, Tang CS
First Hospital, Peking
University, Beijing, China
Objective: To study the role of endogenous gaseous
molecules, nitric oxide (NO) and carbon monoxide (CO) in the development of
hypoxic pulmonary hypertension.
Methods: Hypoxic pulmonary hypertension was created by 2 wk-hypoxic
challenge using a hypoxic chamber. Pulmonary hemodynamics was monitored by
right cardiac catheterization and micro- and ultra pulmonary arterial
structure was examined with light and electric microscope. Plasma and
tissue NO and CO levels were measured by spectrophotometry.
Immunohistochemistry and in situ hybridyzation were used for protein and
mRNA expressions of eNOS, HO-1, ET-1, PDGF-1, collagen-1, Fas, PCNA.
Apoptosis of pulmonary artery SMC and EC were examined by TUNEL methods.
Results: After 2-wk hypoxic challenge, pulmonary artery
pressure was obviously elevated and micro- and ultra-structural analysis
showed an obvious pulmonary structural remodeling with up-regulated
expression of PCNA and collagen-1 expressions by pulmonary arteries
inhibited apoptosis of pulmonary arteries. In pulmonary hypertensive rats
plasma and lung tissue concentrations of NO were significantly decreased
and the protein and gene expressions of eNOS were reduced by pulmonary
arteries. However, plasma and lung tissue concentrations of CO were
significantly increased and the protein and gene expressions of HO-1 were
augmented by pulmonary arteries. L-Arginine significantly attenuated
pulmonary hypertension and pulmonary structural remodeling. But NOS
inhibitor, L-NAME, augmented pulmonary hypertension as well as pulmonary
structural remodeling. ZnPP, a HO inhibitor, augmented pulmonary artery
pressure and pulmonary structural remodeling. Conclusion: Endogenous NO and CO systems might play an
important role in the development of hypoxic pulmonary hypertension.