Guinea histamine-induced bronchoconstriction

Inhibition of PDE IV contributed to relaxation of airway smooth muscle and the prevention of proinflammatory cell activation. However, important side effects limited their therapeutic effects. In order to obtain new data on lignans as PDE inhibitors, Iwasaki et al. [204] synthesised a series of 1-aryl-2,3-bis(hydroxymethyl)naphthalene lignans and evaluated their ability to selectively inhibit PDE IV isolated from guinea pig and the histamine-induced and antigen-induced bronchoconstriction in the guinea pig. The more potent and selective compounds were the N-alkylpyridone derivatives (ring at C-l), and the most potent of these was 6,7-diethoxy-2,3-bis... 

PGF2g caused bronchodilatation in the cat and guinea plg. ° PGF2oi produced bronchoconstriction in man. Human asthmatics were 8000 times more sensitive to the bronchoconstrictor effects of PGF2 than were normals and only 10 times more sensitive to histamine-induced broncho-spasm. It has been suggested that the endogenous PGF/PGE ratio may be critical in asthmatics, but this awaits definition. 

It was hypothesized that airway tone may be affected by inhalation of NO. Dupuy et al. (1992) reported a reduction in bronchoconstriction with NO, studying open chest guinea pigs in a body plethysmograph during provocation with intravenous methacholine. A dose-dependent relaxation between 5 and 300 ppm NO was noted, with normalization of the reduced compliance at inhaled doses above 100 ppm NO. In the same model provocation with histamine, leukotriene D4, and neurokinin A was studied. Inhaled NO reverses bronchoconstriction induced by all of these inflammatory mediators (Dupuy et al., 1993a). Work with methylene blue and NO inhalation... 

Aerosol-administered PGEj prevents bronchoconstriction which has been induced by histamine aerosol. The bronchodilator properties of this prostaglandin were shown to be greater in the guinea-pig and monkey compared with the dog [271, 272],... 

The generation of thromboxanes caused by histamine or SRS-A can be inhibited in the guinea pig by non-steroidal anti-inflammatory drugs [285], however without significantly reducing the bronchoconstriction [286]. On the other hand, these drugs prevented both the increased airway resistance and the thromboxane formation induced by bradykinin [286]. 

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