IBUPROFEN AUGMENTS BRADYKININ-INDUCED GLYCOCONJUGATE SECRETION BY HUMAN NASAL-MUCOSA INVIVO

Bradykinin (BK) stimulates vascular permeability and glycoconjugate secretion in human nasal mucosa. Since some of the effects of BK may be mediated by autocrine generation of arachidonic acid metabolites, the influence of ibuprofen, a cyclooxygenase inhibitor, on BK-induced nasal secretion was studied. Six normal male subjects had nasal provocations with 0, 10, 100, and 1000 nmol of BK before and after treatment with 400 mg of ibuprofen. Secretions were collected by nasal lavage. Total protein (marker of protein secretion), glycoconjugate (mucous cell marker), lysozyme (serous cell marker), and albumin (marker of vascular permeability) were measured. Basal glycoconjugate secretion was higher after ibuprofen (219 +/- 32-mu-g/ml) than before (81 +/- 56 -mu-g/ml; p < 0.05 by analysis of variance). BK stimulated significant, dose-dependent albumin, total protein, and glycoconjugate secretion. Lysozyme secretion was not stimulated. BK (1000 nmol) significantly increased total protein secretion, tenfold to twentyfold, and albumin secretion by 40-fold to 60-fold. Ibuprofen did not alter BK-induced total protein or albumin secretion. Glycoconjugate secretion after ibuprofen treatment was significantly higher than normal at 10 nmol (p < 0.05), 100 nmol (p < 0.02), and 1000 nmol of BK (519-mu-g/ml +/- 74 versus 213 +/- 15-mu-g/ml; p < 0.05). Therefore, BK induces vascular permeability and exocytosis from glycoconjugate-containing cells but does not stimulate serous cells. Ibuprofen increases baseline secretion of glycoconjugate and enhances BK-induced glycoconjugate secretion. Ibuprofen does not alter BK-induced vascular permeability.