Role of neuropeptides in acetylcholine-induced edema in isolated and perfused rabbit lungs

• Published in: The Journal of pharmacology and experimental therapeutics Vol. 266; no. 2; p. 483
• Main Authors: Delaunois, A, Gustin, P, Ansay, M
• Format: Journal Article
• Language: English
• Published: United States 01-08-1993
• Subjects: Acetylcholine - pharmacology; Animals; Arachidonic Acid - metabolism; Capillary Permeability - drug effects; Capsaicin - pharmacology; Female; Male; Neuropeptides - physiology; Papaverine - pharmacology; Perfusion; Pulmonary Edema - chemically induced; Pulmonary Edema - metabolism; Pulmonary Edema - physiopathology; Rabbits; Receptors, Serotonin - physiology; Serotonin - pharmacology; Substance P - pharmacology
• ISSN: 0022-3565

Changes in pulmonary endothelial permeability and in microvascular hemodynamics in response to cumulative concentrations of acetylcholine (ACh) (10(-8) M to 10(-5) M) were investigated in isolated, perfused rabbit lungs. The total pressure gradient was partitioned into four components: arterial, pre- and postcapillary and venous. The capillary filtration coefficient (Kf, c) also was evaluated. ACh caused a significant increase in arterial and precapillary pressures at concentrations higher than 3 x 10(-6) M. The total pressure gradient and precapillary were significantly increased whereas arterial, postcapillary and venous pressure gradient remained unchanged. In papaverine (3 x 10(-4) M)-pretreated lungs, the vasoconstriction was abolished and a concentration-dependent increase in Kf,c was recorded from 10(-8) to 10(-5) M ACh. This reaction was accompanied by pulmonary edema. Atropine, indomethacin, aspirin, ketanserin, clonidine, morphine and (+/-)-CP 96-345, an antagonist of neurokinin NK1 receptors, completely prevented the effects of ACh on Kf,c. In contrast, cromolyn sodium and SR48968, a neurokinin NK2 antagonist, did not inhibit the response to ACh. Terfenadine together with cimetidine had a partially inhibitory effect. Changes in the Kf, c similar to those observed with ACh were induced by capsaicin (10(-4) M) by exogenous substance P (10(-7) M) and by 5-hydroxytryptamine (5-HT) (10(-4) M). The effects of SP were inhibited by aspirin, (+/-)-CP 96,345 and ketanserin, but not by atropine and antihistaminics. 5-HT effects were prevented by aspirin and not by (+/-)-CP 96,345. It was concluded that ACh-induced pulmonary edema was due to an increase in the capillary filtration coefficient.