Basic features of hypoxic pulmonary vasoconstriction in mice.
Hypoxic pulmonary vasoconstriction (HPV) matches lung perfusion with ventilation which tends to optimize pulmonary gas exchange. Investigations using genetically engineered mice represent a promising approach to understand the underlying mechanisms. Our goal was to characterize basic features of HPV in the isolated buffer-perfused and ventilated mouse lung system. HPV was reproducible for several hours when ventilating the lungs with 1% O2 (10 min) alternated with normoxic ventilation periods (21% O2, 15 min). HPV was well elicitable and most constant using Krebs-Henseleit buffer with the addition of hydroxyethylamylopectin as an oncotic agent. Inhibition of both lung NO and prostanoid formation amplified HPV in an over-additive fashion. HPV was higher in BALB/c mive as compared to C57BL/6 mice, and was approximately threefold enhanced under positive pressure ventilation as compared to negative pressure ventilation. A three hour hypoxic ventilation period resulted in a biphasic vasoconstrictor response with loss of posthypoxic vasodilatation. In summary, we have characterised HPV and established an experimental set-up optimized for investigation of the basic mechanisms of HPV in mice.
Weissmann
Norbert
N
Department of Internal Medicine, Justus-Liebig-University Giessen, Klinikstrasse 36, 35392 Giessen, Germany. norbert.weissmann@innere.med.uni-giessen.de
Akkayagil
Ercan
E
Quanz
Karin
K
Schermuly
Ralph Theo
RT
Ghofrani
Hossein Ardeschir
HA
Fink
Ludger
L
Hänze
Jörg
J
Rose
Frank
F
Seeger
Werner
W
Grimminger
Friedrich
F
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000687:Amylopectin / Q000031:analogs & derivatives* / Q000378:metabolism; D000818:Animals; D001241:Aspirin / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology*; D004347:Drug Interactions; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000860:Hypoxia / Q000503:physiopathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D010100:Oxygen / Q000378:metabolism*; D011651:Pulmonary Artery / Q000187:drug effects / Q000503:physiopathology*; D011652:Pulmonary Circulation / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000502:physiology; D013045:Species Specificity; D013990:Tidal Volume / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D019323:omega-N-Methylarginine / Q000494:pharmacology
D004791:Enzyme Inhibitors; D014662:Vasoconstrictor Agents; D019323:omega-N-Methylarginine; C018317:hydroxyethylamylopectin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000687:Amylopectin; D001241:Aspirin; D010100:Oxygen