Cyclic Nucleotide Metabolism in Experimental Bronchial Constriction in Rabbits

Abstract

In anesthetized, spontaneously breathing rabbits, intratracheally administered isotonic saline, acetylcholine (Ach) and histamine (His) induced an increase of airway resistance up to 183, 571, and 312%, respectively, compared with untreated controls. This was accompanied by a decrease of the arterial pO₂. Bilateral cervical vagotomy led to nearly complete inhibition of the saline- and Ach-induced bronchoconstriction, whereas the His effect was only reduced to 202%. Vagotomy did not improve the arterial pO₂. While the bronchoconstrictive effects of isotonic saline and Ach revealed a significant linear correlation with the increased cGMP/cAMP ratio, His did not cause an alteration of the cGMP/ cAMP ratio to a degree that corresponds to its bronchoconstrictive activity. These data indicate that (1) bronchoconstriction-inducing agents may act (a) by stimulation of the parasympathetic nerve or (b) by contracting smooth muscles directly; (2) alveolar ventilation is not regulated by the parasympathetic nerve, and (3) bronchoconstriction induced by parasympathetic stimulation is associated with or mediated by an increase of the cGMP/ cAMP ratio

Wirkung von Acetylcholin- und Histamininhalationen sowie Hypoxie auf die arterielle Plasma-Histaminkonzentration (Versuche an Hunden)

“…Acetylcholin wie Histamin 16sen bronchospastlsche Reaktionen aus; es wird von beiden Substanzen diskutiert, dab sie die Histaminfreisetzung aus Mastzellen f6rdern (Ffigner 1977;S6renby 1975;Morr 1979; Gold et al 1977; Richardson et al 1973;Beaven 1976;Kaukel et al 1978;Kaliner 1977;Nisam et al 1978). Die eigentliche Bronchokonstriktion wfirde dann immer fiber das aus Mastzellen freigesetzte Histamin und die Folgemediatoren zustande kommen.…”

Chronic Hypoxia: Evidence for Parasympathetic Stimulation and cGMP/cAMP-Mediated DNA Synthesis

“…/J-Adrenergic stimulation with orciprenaline or inhibition of phosphodiesterase with aminophylline leads to dilatation of the pulmonary resist ance vessels and to a concomitant increase of the lung cAMP levels [21]; on the other hand, an increase of the pulmonary vascular resistance during acute hypoxia is accompa nied by a parallel elevation of the cGMP/cAMP ratio [12]. With Ach coming into the play, the matter seems to be even more complicated.…”

“…Acute hypoxia stimulates the v. Euler-Liljestrand mechanism, resulting in pulmonary vascular constriction [5] and concomitant changes of the lung tissue cGMP/cAMP ratio that are closely related to the time course of the pulmo nary vascular resistance [12]. Chronic hypoxia in its initial stage leads to a strong increase of the lung tissue DNA synthesis reflecting marked cell proliferation [24], Acetylcholine (Ach) has been known to be a potent vasodilator of the pulmonary vasculature [6,14], and recent evidence has been accumulated that parasympathetic stimulation can turn on mitosis [18].…”