The effects, mechanisms and actions of kinins in rhinitis and asthma

Rajakulasingam, Karalasingam (1996) The effects, mechanisms and actions of kinins in rhinitis and asthma. University of Southampton, Doctoral Thesis.

Abstract

Within the nose, nasal challenge with bradykinin and kallidin induce rhinorrhoea and nasal blockage. This response was shown to be mediated via B2 receptors as the selective B1 receptor agonist [des-arg⁹]-bradykinin had no effect. Both B2 agonists, bradykinin and kallidin were found to be equally potent in inducing these changes. These nasal effects were not mediated individually by histaminergic or cholinergic mechanisms as the oral H₁-receptor antagonist, terfenadine, and the anti-muscarinic agent, ipratropium bromide, had no effect on the response. Comparative studies with capsaicin also suggested that the action of bradykinin was not mediated via "C" sensory fibres. Qualitatively the effect of bradykinin in rhinitic and non-rhinitic subjects was similar although quantitatively there was an exaggerated nasal obstructive response in patients with rhinitis consistent with nasal hyperreactivity in active disease.

Within the lower airways, inhalation of bradykinin induced dose-dependent bronchospasm in patients with asthma consistent with lower airway hyperresponsiveness in this disease. The observed bronchial reactivity (PC₂₀) to bradykinin did not correlate to that of histamine, suggesting an alternative mechanism of action. The bronchoconstrictor effects of bradykinin were shown to be inhibited by inhaled frusemide which is known to interfere with neural mechanisms, but to be uninfluenced by BAY u 3405, a thromboxane receptor antagonist, which inhibited PGD₂-induced bronchoconstriction. The lower airway but not upper airway responses to bradykinin were associated with refractoriness and, cross refractoriness was demonstrated between the constrictor responses to hypertonic saline and bradykinin challenge in asthma. No interactive effect was, however, evident between bradykinin and either histamine or PGD₂.

These studies suggest the potential role of kinins in both rhinitis and asthma. By studying both the upper and lower airways it has been possible to address both the vascular and bronchoconstrictor (smooth muscle) effects of kinins. These studies indicate both direct (vascular) and indirect (constrictor) mechanism of actions for kinins.

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