Respiratory Physiology & Neurobiology 139 (2004) 191–202 Basic features of hypoxic pulmonary vasoconstriction in mice  Norbert Weissmann ∗ , Ercan Akkayagil, Karin Quanz, Ralph Theo Schermuly, Hossein Ardeschir Ghofrani, Ludger Fink, Jörg Hänze, Frank Rose, Werner Seeger, Friedrich Grimminger Department of Internal Medicine, Justus-Liebig-University Giessen, Klinikstrasse 36, 35392 Giessen, Germany Accepted 9 October 2003 Abstract 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% O 2 (10 min) alternated with normoxic ventilation periods (21% O 2 , 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. © 2003 Elsevier B.V. All rights reserved. Keywords: Hypoxic, pulmonary vasoconstriction; Mammals, mouse; Mediators, NO; Perfusion, lung 1. Introduction Hypoxic pulmonary vasoconstriction (HPV) is a physiological mechanism which tends to match lung perfusion with ventilation and improves pulmonary gas exchange. Great effort has been made since the description of von Euler and Liljestrand in 1946 to  Portions of the doctoral thesis of Ercan Akkayagil are incor- porated into this report. ∗ Corresponding author. Tel.: +49-641-99-42351; fax: +49-641-99-42419. E-mail address: norbert.weissmann@innere.med.uni-giessen.de (N. Weissmann). identify the cell(s) responsible for O 2 -sensing, the sensor mechanism(s), and the pathway(s) of signal transduction leading to contraction of the vascular smooth muscle cells in the precapillary resistance vessels, thought to be the predominant site of HPV (Fishman, 1976; Staub, 1985). Isolated, perfused, and ventilated lungs of different species have been investi- gated frequently to identify the underlying regulatory process. Compared to experiments in isolated cells or pulmonary artery rings, investigations using iso- lated lungs have the advantage of maintaining natural cell–cell contacts and physiological microenviron- ments. In spite of these efforts, the basic mechanisms of HPV are far from being thoroughly described, 1569-9048/$ – see front matter © 2003 Elsevier B.V. All rights reserved. doi:10.1016/j.resp.2003.10.003