Effects of bradykinin receptor antagonists on antigen‐induced respiratory distress, airway hyperresponsiveness and eosinophilia in guinea‐pigs

Abstract

1 We examined effects of bradykinin (BK) receptor antagonists on airway hyperresponsiveness and eosinophilia in sensitized guinea-pigs that had been administered single, as well as repeated (chronic) challenges with inhaled ovalbumin. In addition, the effects of BK antagonists on antigen-induced respiratory distress during the chronic study were noted. 2 At 24 h following single antigen challenge, guinea-pigs exhibited airway hyperresponsiveness to the bronchoconstrictor effect of i.v. histamine, characterized by a left shift in the dose-response curve. In addition, responses to the maximum dose of histamine that could be used were significantly increased in hyperresponsive guinea-pigs. (NPC 16731). NPC 16731 also abolished antigen-induced cyanosis, and delayed the onset of dyspnoea, doubling the time taken for animals to exhibit respiratory distress. 6 The ability of BK receptor antagonists to inhibit antigen-induced airway hyperresponsiveness, in addition to eosinophilia, indicates an important role for endogenous kinins. Moreover, the abrogation of eosinophil infiltration suggests that BK has a significant function in maintaining allergic inflammation of the airways.

Bradykinin Stimulates Type II Alveolar Cells to Release Neutrophil and Monocyte Chemotactic Activity and Inflammatory Cytokines

“…37 Although the BK receptor on A549 cells is not identified, the present study suggests that both BKB1 and BKB2 receptors are concerned with the release of NCA and MCA. Thus, the receptor responsible for the release of IL-8, G-CSF, and MCP-1 may involve both BKB1 and BKB2 receptors.…”

Bradykinin B2 Receptor Mediates NF-κB Activation and Cyclooxygenase-2 Expression via the Ras/Raf-1/ERK Pathway in Human Airway Epithelial Cells

“…Allergen challenge studies have also established that BK plays a pivotal role in the initiation of chronic airway inflammation (37). B2 BK receptor antagonists effectively block the development of the late-phase airway response as well as the development of bronchial hyperresponsiveness following allergen challenge in a number of different experimental animal models (3,4). To explore the mechanism by which BK promotes airway inflammation, we examined the ability of BK to regulate COX-2 expression in airway epithelial cells.…”

“…The release of BK is known to mediate multiple proinflammatory effects including smooth muscle contraction, vasodilation, increased vascular permeability, eicosanoid synthesis, and neuropeptide release (1,2). Furthermore, BK has been shown to play a critical role in the development of airway hyperresponsiveness in experimental models of airway inflammation (3)(4)(5). To elucidate the role of BK in this process, we assessed the effect of BK on cyclooxygenase-2 (COX-2) expression in human airway epithelial cells.…”

“…B radykinin (BK) 3 is rapidly generated following inflammation or injury (1). The release of BK is known to mediate multiple proinflammatory effects including smooth muscle contraction, vasodilation, increased vascular permeability, eicosanoid synthesis, and neuropeptide release (1,2).…”

The role of bradykinin in lung ischemia-reperfusion injury in a rat lung transplantation model

“…antagonists play a protective role against ischemia/reperfusion (I/R) injury, particularly in transplantation [2][3][4][5] , but the significance of bradykinin in IR and the relationship between bradykinin and CD26/DPP-4 are not completely understood. It is accepted that the kallikrein-kinin system expresses potent biological activities through its final product, bradykinin 6 , and that bradykinin acts via two receptor subtypes.…”