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Allergic lung inflammation induces pulmonary vascular hyperresponsiveness

¹ Dept of Internal Medicine, Infectious Diseases and Respiratory Medicine, and ² Dept of Paediatric Pneumology and Immunology, Charité, Universitätsmedizin Berlin, Berlin, Germany.

CORRESPONDENCE: M. Witzenrath, Dept of Internal Medicine, Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, Schumannstr 20/21, 10117 Berlin, Germany. Fax: 49 30450553979. E-mail: martin.witzenrath{at}charite.de

Keywords: Allergic inflammation, 5-hydroxytryptamine, isolated mouse lung, ovalbumin, pulmonary hypertension, serotonin

Received: July 8, 2005
Accepted March 19, 2006

Pulmonary arterial vasoconstriction is an important early component of pulmonary hypertension. Inflammatory mechanisms play a prominent role in the pathogenesis of pulmonary hypertension. The present authors investigated the potential role of acute allergic lung inflammation for alterations in pulmonary haemodynamics.

BALB/c mice were intraperitoneally sensitised to ovalbumin and challenged by ovalbumin inhalation. Subsequently, lungs were ventilated and perfused ex vivo, and pulmonary arterial pressure (P_pa) was continuously monitored.

Isolated perfused lungs of allergen-sensitised and -challenged mice showed five-fold enhanced P_pa responses to serotonin, which is reported to be a significant contributor to pulmonary hypertension in humans. This increase in P_pa was abolished by the serotonin receptor-2A antagonist ketanserin, but not the serotonin receptor-1B antagonist GR127935. Intracellular signalling to serotonin involved phosphatidylcholine-specific phospholipase C and protein kinase C, as well as Rho-kinase, as assessed by employing the specific inhibitors D609, bisindolylmaleimide and Y27632, respectively. In addition to serotonin, impressively enhanced P_pa increases in allergic lungs were also evoked by the thromboxane receptor agonist U46619 [GenBank] , angiotensin II and endothelin-1.

In conclusion, allergic lung inflammation was accompanied by impressive pulmonary vascular hyperresponsiveness. These results suggest a possible role for allergic inflammation in the development of pulmonary arterial hypertension.

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