Am. J. Respir. Crit. Care Med., Volume 157, Number 2, February 1998, 547-552

Endogenous Nitric Oxide Inhibits Bronchoconstriction Induced by Cold-Air Inhalation in Guinea Pigs
Role of Kinins

SHIGEMI YOSHIHARA, JAY A. NADEL, MICHELA FIGINI, COSTANZA EMANUELI, PHILIPPE PRADELLES, and PIERANGELO GEPPETTI

First Department of Pediatrics, Dokkyo University School of Medicine, Tochigi, Japan; Cardiovascular Research Institute and Departments of Medicine and Physiology, University of California, San Francisco, San Francisco, California; Department of Experimental and Clinical Medicine, Pharmacology Unit, University of Ferrara, Ferrara, Italy; and SPI, CEN-Saclay, Gif-sur-Yvette, France

Inhalation of cold air in guinea pigs increases total pulmonary resistance (RL), an effect that is mediated by kinins and tachykinins. Bronchoconstriction induced by bradykinin (BK) inhalation in guinea pigs is markedly inhibited by nitric oxide (NO) release from the airway epithelium. We investigated whether endogenous NO modulates the increase in RL induced by inhalation of cold air. In anesthetized and artificially ventilated guinea pigs pretreated with atropine, cold-air inhalation (13° C in the trachea) for 5 min did not increase RL. Pretreatment with intravenous N^G-nitro-L-arginine methyl ester (L-NAME) (but not with its inactive enantiomer, D-NAME) increased RL, an effect reversed by L-Arg. The increase in RL induced by cold air after L-NAME was abolished by the tachykinin NK₂-receptor antagonist SR 48968 or the kinin B₂ -receptor antagonist, HOE 140. After administration of SR 48968, inhalation of cold air reduced baseline airway tone. However, after HOE 140, cold-air inhalation did not affect baseline airway tone. L-NAME exaggerated the bronchoconstriction induced by BK. However, L-NAME did not affect capsaicin-induced bronchoconstriction. BK increased cyclic guanosine monophosphate (cGMP) levels in strips of guinea pig trachealis muscle in vitro, whereas the selective tachykinin NK₂-receptor agonist [Ala⁸]neurokinin A () was without effect. The present data suggest that bronchoconstriction induced by cold-air inhalation and mediated by kinin and tachykinin release is inhibited by endogenous NO, and that kinins, but not tachykinins or cold air alone, release bronchorelaxant NO.

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