Allergic lung inflammation induces pulmonary vascular hyperresponsiveness

Abstract

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 (Ppa) was continuously monitored.Isolated perfused lungs of allergen-sensitised and -challenged mice showed five-fold enhanced Ppa responses to serotonin, which is reported to be a significant contributor to pulmonary hypertension in humans. This increase in Ppa 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 Ppa 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 pulmonary arterial hypertension.

Synergistic effects of apelin and leptin on isolated rat pulmonary arteries

“…Increased pulmonary arterial vascular tone is an important early component of pulmonary vascular disease [14]. It has been demonstrated that a specific antigen challenge causes an increase in responsiveness to contractile agonists [14] and a decrease of endothelium-dependent relaxant responses to acetylcholine [15,16]. Published data confirm that damage to the endothelium may play an important role in the development of pulmonary vascular diseases in both humans and experimental models [17,18].…”

“…We compared its effects in normal rats and in two experimental model rats that combine the inflammation and endothelial dysfunction of pulmonary vessels: the ovalbumin (OVA)-induced allergic airway disease and monocrotaline (MCT)-induced pulmonary hypertension. Increased pulmonary arterial vascular tone is an important early component of pulmonary vascular disease [14]. It has been demonstrated that a specific antigen challenge causes an increase in responsiveness to contractile agonists [14] and a decrease of endothelium-dependent relaxant responses to acetylcholine [15,16].…”

Pulmonary Vascular Disease in the Developing World

“…29 Some cytokines also alter the amounts of various surface components of the blood vessel wall and significantly decrease the functional cell surface thrombin receptor (thrombomodulin), thus promoting coagulation in the pulmonary vessels. 30 Other changes in the inflammatory process may cause endothelial dysregulation of cell-cell adhesion and transendothelial migration, which contribute to the pulmonary vasculopathy.…”

Effect of Both Ultraviolet B Irradiation and Histamine Receptor Function on Allergic Responses to an Inhaled Antigen

“…In contrast to other animal models of allergic respiratory disease that used the i.p. route for sensitization (8,34), this model was completely intranasal for sensitization, boost, and challenge, and as such better mimics the route through which human respiratory sensitization to allergens occurs. Furthermore, this model was adjuvant-free and thus the immune responses observed were due entirely to Ag exposure and were not skewed by the use of adjuvants such as aluminum hydroxide.…”