In-vitro exposure of guinea pig main bronchi to 2.5 ppm of nitrogen dioxide does not alter airway smooth muscle response.

In order to investigate whether the oxidant airborne pollutant nitrogen dioxide (NO2) affects airway smooth muscle responsiveness, the contractile response of guinea pig main bronchi after in vitro exposure to 2.5 ppm of nitrogen dioxide was studied. Main bronchi were cannulated and exposed for 2 or 4 h to a constant flow of either NO2 or air. After exposure, bronchial rings were obtained and placed in a 37 degrees C jacketed organ bath filled with Krebs-Henseleit solution. Concentration-response curves were performed for acetylcholine (10(-9)-10(-3) M), substance P (10(-9)-10(-4) M), and neurokinin A (10(-10)-10(-5) M), and voltage-response curves (12-28 V) were performed for electrical field stimulation. There was no significant difference in either the smooth muscle maximal contractile response, or sensitivity between the bronchi exposed to NO2 and those exposed to air. We conclude that in vitro exposure to 2.5 ppm of NO2 does not alter airway smooth muscle responsiveness in guinea pigs.

In vitro exposure to nitrogen dioxide (NO2) does not alter bronchial smooth muscle responsiveness in ovalbumin-sensitized guinea-pigs.

The aim of this study was to investigate whether in vitro exposure to NO2 affects responsiveness in ovalbumin-sensitized guinea-pig bronchi. Twenty-three animals were sensitized by three weekly intraperitoneal injections of 1 mg ovalbumin in saline with Freund's adjuvant; twenty-one control guinea-pigs received the diluent alone. From each animal, the two main bronchi were obtained and cannulated, then exposed in vitro to a constant intraluminal flow of: (i) either air or 2.5 ppm NO2 with four spikes of 10 ppm NO2 for 2 h; (ii) either air or 10 ppm NO2 for 4 h. A bronchial ring obtained from each animal before exposure was kept in aerated Krebs-Henseleit solution. Rings from bronchi exposed to air, NO2, or kept in Krebs solution were studied isometrically. We performed overall and non-adrenergic non-cholinergic voltage-response curves to electrical field stimulation, concentration-response curves to acetylcholine and to neurokinin A, followed by administration of 10 mg/ml ovalbumin. We did not find any significant difference in bronchial smooth muscle responsiveness between nonexposed, air-exposed and NO2-exposed bronchi, as well as between bronchi from control and sensitized animals. We conclude that in vitro exposure to NO2 does not alter bronchial smooth muscle responsiveness to either specific or non-specific stimuli.

The effect of compound 48/80 on contractions induced by toluene diisocyanate in isolated guinea-pig bronchus.

We have investigated the ability of compound 48/80 and of histamine H1 and H2 receptor antagonists to inhibit toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. Compound 48/80 (100 micrograms/ml) significantly inhibited toluene diisocyanate-induced contractions. By contrast, the two histamine H1 and H2 receptor antagonists, chlorpheniramine (10 microM) and cimetidine, (10 microM) did not affect toluene diisocyanate-induced contractions, but significantly inhibited contractions induced by exogenously applied histamine (100 microM) and by 48/80. We investigated which mechanisms 48/80 used to inhibit toluene diisocyanate-induced contractions, paying particular attention to the possible involvement of capsaicin-sensitive primary afferents. In vitro capsaicin desensitization (10 microM for 30 min followed by washing) significantly reduced compound 48/80-induced contractions. A capsaicin-resistant component of contraction was also evident. Ruthenium red (3 microM), an inorganic dye which acts as a selective functional antagonist of capsaicin, did not affect 48/80-induced contraction. MEN 10,207 (Tyr5,D-Trp6,8,9,Arg10)-neurokinin A (4-10) (3 microM) a selective antagonist of NK2-tachykinin receptors significantly reduced 48/80-induced contractions. These results show that compound 48/80 inhibits toluene diisocyanate-induced contractions in isolated guinea-pig bronchi. It is likely that two mechanisms are involved in the inhibition: (1) the release of mediators other than histamine by mast cells, (2) an effect of 48/80 on sensory nerves.

Hereditary heparin cofactor II deficiency and thrombosis: report of six patients belonging to two separate kindreds.

We describe six patients belonging to two families with congenital heparin cofactor II deficiency (HC II). The affected members had low levels of HC II antigen and activity, and no abnormalities in HC II electrophoretic mobility were detected in the presence of heparin or dermatan sulphate during the first migration of crossed immunoelectrophoresis. These data suggested that patients had a type I (true) HC II deficiency. The association of thrombotic manifestations with congenital HC II deficiency has not been completely clarified. In these two families, thrombotic events occurred in two out of six affected members. In addition, there was a high incidence of spontaneous abortion in the affected females. Finally, the association of congenital HC II deficiency with angiomatosis was also observed in one patient.