N. Weissmann et al., NO and reactive oxygen species are involved in biphasic hypoxic vasoconstriction of isolated rabbit lungs, AM J P-LUNG, 280(4), 2001, pp. L638-L645
Citations number
32
Categorie Soggetti
da verificare
Journal title
AMERICAN JOURNAL OF PHYSIOLOGY-LUNG CELLULAR AND MOLECULAR PHYSIOLOGY
Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventil
ation but may also result in chronic pulmonary hypertension. It has not bee
n clarified whether acute HPV and the response to prolonged alveolar hypoxi
a are triggered by identical mechanisms. We characterized the vascular resp
onse to sustained hypoxic ventilation (3% O-2 for 120-180 min) in isolated
rabbit lungs. Hypoxia provoked a biphasic increase in pulmonary arterial pr
essure (PAP). Persistent PAP elevation was observed after termination of hy
poxia. Total blockage of lung nitric oxide (NO) formation by N-G-monomethyl
-L-arginine caused a two- to threefold amplification of acute HPV, the sust
ained pressor response, and the loss of posthypoxic relaxation. This amplif
ication was only moderate when NO formation was partially blocked by the in
ducible NO synthase inhibitor S-methylisothiourea. The superoxide scavenger
nitro blue tetrazolium and the superoxide dismutase inhibitor triethylenet
etramine reduced the initial vasoconstrictor response, the prolonged PAP in
crease, and the loss of posthypoxic vasorelaxation to a similar extent. The
NAD(P)H oxidase inhibitor diphenyleneiodonium nearly fully blocked the lat
e vascular responses to hypoxia in a dose that effected a decrease to half
of the acute HPV. In conclusion, as similarly suggested for acute HPV, lung
NO synthesis and the superoxide-hydrogen peroxide axis appear to be implic
ated in the prolonged pressor response and the posthypoxic loss of vasorela
xation in perfused rabbit lungs undergoing 2-3 h of hypoxic ventilation.