Effects of disodium cromoglycate on hypoxic pulmonary hypertension in dogs
Rengo, F.; Trimarco, B.; Ricciardelli, B.; Volpe, M.; Violini, R.; Saccá, L.; Chiariello, M.
Journal of Pharmacology and Experimental Therapeutics 211(3): 686-689
1979
ISSN/ISBN: 0022-3565 PMID: 117097 Document Number: 148729
Recent reports furnished contrasting data concerning the ability of disodium cromoglycate (DSCG) to prevent hypoxic pulmonary hypertension. This study was designed to ascertain whether or not this drug possesses such an effect and also to clarify the mechanism of action of DSCG. In dogs, hypoxia was induced and hemodynamic measurements performed. Histamine blood concentration was also assessed. Hypoxia significantly increased mean pulmonary artery pressure (from 15 .+-. 1 mm Hg at rest to 25 .+-. 2 mm Hg after hypoxia, P < .01). Blood histamine content in the pulmonary artery and in the inferior vena cava also rose significantly. Pretreatment with 8 mg/kg of DSCG, a drug which inhibits mast cell degranulation and histamine release, abolished both hypoxia-induced responses. To assess whether or not the pulmonary hypertension and the increase in blood histamine levels were linked by a cause-effect relationship, the effects of hypoxia after i.v. administration of 1, 2.5, 5 and 8 mg/kg of DSCG were investigated. The administration of DSCG was able to abolish completely the hypoxia-induced increase in blood histamine levels at a dose as low as 1 mg/kg. To achieve the complete inhibition of hypoxic pulmonary hypertension, 8 mg/kg of DSCG were needed. In dogs pretreated with atropine, DSCG (8 mg/kg) was unable to block hypoxia-induced pulmonary hypertension (15 .+-. 1 mm Hg at rest and 23 .+-. 2 mm Hg after hypoxia, P < .01), although atropine did not exert any effect on histamine concentration; actually, the hypoxia-induced increase in histamine content was inhibited similarly when DSCG was given alone and after atropine. DSCG is apparently able in dogs to prevent pulmonary hypertension induced by hypoxia and this effect is related to a sharp increase in vagal tone due to pulmonary chemoreflexes.