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Strielkov, Ievgen; Krause, Nicole Catherine; Sommer, Natascha; Schermuly, Ralph Theo; Ghofrani, Hossein Ardeschir; Grimminger, Friedrich; Gudermann, Thomas; Dietrich, Alexander und Weissmann, Norbert (2018): Hypoxic pulmonary vasoconstriction in isolated mouse pulmonary arterial vessels. In: Experimental Physiology, Bd. 103, Nr. 9: S. 1185-1191

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Abstract

Hypoxic pulmonary vasoconstriction (HPV) is a physiological response of pulmonary arteries, which adapts lung perfusion to regional ventilation. The properties of HPV vary significantly between animal species. Despite extensive use of mouse models in studies of HPV, this physiological response has never been characterized in isolated mouse pulmonary arteries in detail. Using wire myography, we investigated the effect of 80min exposure to hypoxia on the tone in mouse pulmonary arteries of different generations in the presence and absence of preconstriction. Hypoxia induced a sustained relaxation in non-preconstricted extrapulmonary arteries (500-700m in diameter), but not in the presence of KCl-induced preconstriction. Large intrapulmonary arteries (450-650m in diameter) did not exhibit a significant response to the hypoxic challenge. In contrast, in small intrapulmonary arteries (80-200m in diameter), hypoxia elicited a slowly developing sustained constriction, which was independent of the endothelium. The response was significantly potentiated in arteries preconstricted with KCl, but not with U46619. Hypoxic pulmonary vasoconstriction was not altered in pulmonary arteries of TRPC6-deficient mice, which suggests that this response corresponds to the sustained phase of biphasic HPV observed earlier in isolated, buffer-perfused and ventilated mouse lungs. In conclusion, we have established a protocol that allows the study of sustained HPV in isolated mouse pulmonary arteries. The data obtained might be useful for future studies of the mechanisms of HPV in mice.

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