Effect of Ovalbumin Challenge on Endothelial Reactivity of Pulmonary Arteries from Sensitized Guinea-pigs

Abstract

Summary: It has been generally demonstrated that sensitization process and/or specific antigen challenge causes an increase in the responsiveness of airway smooth muscle preparations to contractile agonists. However, there is no report elucidating such modifications in vascular preparations. In this study, we examined the influence of ovalbumin sensitization and challenge on the reactivity of guinea-pig pulmonary arteries to various vasoactive agents. Guinea-pigs were actively sensitized to ovalbumin (10 mg/kg) by i p injections on days 1, 3 and 5. Beginning 21 days after the last injection, animals were challenged with ovalbumin either in vitro or in vivo. The effects of sensitization process and challenge were studied on endothelium-dependent and -independent responses of guinea-pig pulmonary arteries.

Ovalbumin challenge but not sensitization process significantly reduced the endothelium-dependent relaxant responses to acetylcholine and histamine. Similar reductions were also observed in the responses of calcium ionophore, A 23187. However, no alteration was observed in the responses to glyceryl trinitrate and potassium chloride which excludes an abnormality in the relaxant and contractile capacities of pulmonary artery smooth muscle following sensitization and challenge. In addition, an enhancement was observed in the contractile effect of phenylephrine after ovalbumin sensitization and challenge different from U 46619, a thromboxane analogue, and potassium chloride induced contractions. Incubation of the sensitized arteries with the mast cell stabilizer, disodium cromoglycate but not with the free radical scavenger superoxide dismutase protected the reduced responsiveness to endothelium-dependent vasodilators following challenge.

We conclude that ovalbumin challenge causes an abnormality in endothelial cell reactivity of pulmonary vasculature possibly due to destructive enzymes released from mast cells.