A. Delaunois et al., MODULATORY EFFECT OF NEUROPEPTIDE-Y ON ACETYLCHOLINE-INDUCED EDEMA AND VASOCONSTRICTION IN ISOLATED-PERFUSED LUNGS OF RABBIT, British Journal of Pharmacology, 113(3), 1994, pp. 973-981
1 The modulatory role of neuropeptide Y (NPY) on pulmonary oedema indu
ced by acetylcholine and capsaicin was investigated. The effects of NP
Y on the haemodynamic response to acetylcholine, phenylephrine and sub
stance P were also investigated. 2 Isolated, ventilated, exsanguinated
lungs of the rabbit were perfused with a constant flow of recirculati
ng blood-free perfusate. The double/arterial/venous occlusion method w
as used to partition the total pressure gradient (Delta Pt) into four
components: the arterial gradient (Delta Pa), the pre- and post-capill
ary gradients (respectively Delta Pa' and Delta Pv') and the venous pr
essure 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) in
duced a concentration-dependent increase in the Kf,c. Capsaicin (10(-4
) M) and 5-hydroxytryptamine (5-HT) (10(-4) M) also increased this par
ameter. NPY (10(-8) M) completely inhibited the effects of acetylcholi
ne and capsaicin on the Kf,c, without preventing the effects of substa
nce P and 5-HT. 4 Acetylcholine induced concentration-dependent vasoco
nstriction in the precapillary segment. The effect was inhibited by NP
Y and aspirin, an inhibitor of cyclo-oxygenase, while ketanserin, a 5-
HT2 receptor antagonist, and SR140333, a new NK1 antagonist, had no pr
otective effect. Phenylephrine increased Delta Pa at high concentratio
n, an effect also inhibited by NPY and aspirin. Substance P had no sig
nificant haemodynamic effect. When injected together with NPY, substan
ce P (10(-6) M) induced a significant increase in the total pressure g
radient. 5 It was concluded that NPY can protect the lung against acet
ylcholine- and capsaicin-induced oedema via a prejunctional modulatory
effect on the C-fibres. NPY also inhibits acetylcholine-evoked precap
illary and phenylephrine-induced arterial vasoconstriction, probably b
y interfering with cyclo-oxygenase products synthesis.