NO and reactive oxygen species are involved in biphasic hypoxic vasoconstriction of isolated rabbit lungs.
Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventilation but may also result in chronic pulmonary hypertension. It has not been clarified whether acute HPV and the response to prolonged alveolar hypoxia are triggered by identical mechanisms. We characterized the vascular response to sustained hypoxic ventilation (3% O(2) for 120-180 min) in isolated rabbit lungs. Hypoxia provoked a biphasic increase in pulmonary arterial pressure (PAP). Persistent PAP elevation was observed after termination of hypoxia. Total blockage of lung nitric oxide (NO) formation by N(G)-monomethyl-L-arginine caused a two- to threefold amplification of acute HPV, the sustained pressor response, and the loss of posthypoxic relaxation. This amplification was only moderate when NO formation was partially blocked by the inducible NO synthase inhibitor S-methylisothiourea. The superoxide scavenger nitro blue tetrazolium and the superoxide dismutase inhibitor triethylenetetramine reduced the initial vasoconstrictor response, the prolonged PAP increase, and the loss of posthypoxic vasorelaxation to a similar extent. The NAD(P)H oxidase inhibitor diphenyleneiodonium nearly fully blocked the late 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 implicated in the prolonged pressor response and the posthypoxic loss of vasorelaxation in perfused rabbit lungs undergoing 2-3 h of hypoxic ventilation.
Weissmann
N
N
Department of Internal Medicine, Justus-Liebig-University Giessen, Klinikstrasse 36, 35392 Giessen, Germany. Norbert.Weissmann@innere.med.uni-giessen.de
Winterhalder
S
S
Nollen
M
M
Voswinckel
R
R
Quanz
K
K
Ghofrani
H A
HA
Schermuly
R T
RT
Seeger
W
W
Grimminger
F
F
D000818:Animals; D001794:Blood Pressure; D000860:Hypoxia / Q000503:physiopathology*; D066298:In Vitro Techniques; D009569:Nitric Oxide / Q000502:physiology*; D011651:Pulmonary Artery / Q000503:physiopathology; D011652:Pulmonary Circulation; D011817:Rabbits; D017382:Reactive Oxygen Species / Q000502:physiology*; D014661:Vasoconstriction / Q000502:physiology*
D017382:Reactive Oxygen Species; D009569:Nitric Oxide