Modulatory effect of neuropeptide Y on acetylcholine-induced oedema and vasoconstriction in isolated perfused lungs of rabbit.
1. The modulatory role of neuropeptide Y (NPY) on pulmonary oedema induced by acetylcholine and capsaicin was investigated. The effects of NPY on the haemodynamic response to acetylcholine, phenylephrine and substance P were also investigated. 2. Isolated, ventilated, exsanguinated lungs of the rabbit were perfused with a constant flow of recirculating blood-free perfusate. The double/arterial/venous occlusion method was used to partition the total pressure gradient (delta Pt) into four components: the arterial gradient (delta Pa), the pre- and post-capillary gradients (respectively delta Pa' and delta Pv') and the venous pressure gradient (delta Pv). Endothelial permeability was evaluated by measuring the capillary filtration coefficient (Kf,c). 3. Acetylcholine (10(-8) M to 10(-4) M) and substance P (SP, 10(-10) M to 10(-6) M) induced a concentration-dependent increase in the Kf,c. Capsaicin (10(-4) M) and 5-hydroxytryptamine (5-HT) (10(-4) M) also increased this parameter. NPY (10(-8) M) completely inhibited the effects of acetylcholine and capsaicin on the Kf,c, without preventing the effects of substance P and 5-HT. 4. Acetylcholine induced concentration-dependent vasoconstriction in the precapillary segment. The effect was inhibited by NPY and aspirin, an inhibitor of cyclo-oxygenase, while ketanserin, a 5-HT2 receptor antagonist, and SR140333, a new NK1 antagonist, had no protective effect. Phenylephrine increased delta Pa at high concentration, an effect also inhibited by NPY and aspirin. Substance P had no significant haemodynamic effect. When injected together with NPY, substance P (10(-6) M) induced a significant increase in the total pressure gradient. 5. It was concluded that NPY can protect the lung against acetylcholine- and capsaicin-induced oedemavia a prejunctional modulatory effect on the C-fibres. NPY also inhibits acetylcholine-evoked precapillary and phenylephrine-induced arterial vasoconstriction, probably by interfering with cyclo-oxygenase products synthesis.
Delaunois
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A
Department of Pharmacology & Toxicology, Faculty of Veterinary Medicine, University of Liège, Belgium.
Gustin
P
P
Dessy-Doize
C
C
Ansay
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M
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010477:Perfusion; D010539:Permeability; D011654:Pulmonary Edema / Q000517:prevention & control*; D011817:Rabbits; D012701:Serotonin / Q000494:pharmacology; D013373:Substance P / Q000494:pharmacology; D014661:Vasoconstriction / Q000187:drug effects*
D009478:Neuropeptide Y; D012701:Serotonin; D013373:Substance P; D000109:Acetylcholine; D002211:Capsaicin