Role of neuropeptides in acetylcholine-induced edema in isolated and perfused rabbit lungs.
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.(ABSTRACT TRUNCATED AT 250 WORDS)
Delaunois
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Department of Pharmacology, Pharmacotherapy and Toxicology, Faculty of Veterinary Medicine, University of Liege, Belgium.
Gustin
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Ansay
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D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000378:metabolism; D002199:Capillary Permeability / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D008297:Male; D009479:Neuropeptides / Q000502:physiology*; D010208:Papaverine / Q000494:pharmacology; D010477:Perfusion; D011654:Pulmonary Edema / Q000139:chemically induced* / Q000378:metabolism / Q000503:physiopathology; D011817:Rabbits; D011985:Receptors, Serotonin / Q000502:physiology; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology
D009479:Neuropeptides; D011985:Receptors, Serotonin; D016718:Arachidonic Acid; D012701:Serotonin; D013373:Substance P; D010208:Papaverine; D000109:Acetylcholine; D002211:Capsaicin