Allergic lung inflammation induces pulmonary vascular hyperresponsiveness

¹ Dept of Internal Medicine, Infectious Diseases and Respiratory Medicine, Charité, Universitätsmedizin Berlin, 13353 Berlin, Germany
² Dept of paediatric Pneumology and Immunology, Charité, Universitätsmedizin Berlin, 13353 Berlin, Germany

^* To whom correspondence should be addressed. E-mail: martin.witzenrath{at}charite.de.

	Abstract

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

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

Isolated perfused lungs of allergen-sensitized and -challenged mice showed 5-fold enhanced pulmonary arterial pressure responses to serotonin, which is reported to be a significant contributor to pulmonary hypertension in humans. This increase in pulmonary arterial pressure was abolished by the serotonin receptor 2A antagonist ketanserin, but not the serotonin receptor 1B antagonist GR127935. Intracellular signaling to serotonin involved phosphatidylcholine-specific phospholipase C and proteinkinase C, as well as Rho-kinase, as assessed by employing the specific inhibitors D609, bisindolylmaleimide and Y27632, respectively. In addition to serotonin, impressively enhanced pulmonary arterial pressure increases in allergic lungs were also evoked by the thromboxane receptor agonist U46619, 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 PH.

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