Effects of capsaicin on the endothelial permeability in isolated and perfused rabbit lungs.
Changes in pulmonary endothelial permeability and in microvascular hemodynamics in response to capsaicin (10(-4) M) were investigated in isolated, perfused rabbit lungs. Blood-free perfusate was recirculated through ventilated lungs in an isogravimetric state, under zone III conditions with a constant flow. Using the occlusions method, the total pressure gradient between the arterial and the venous levels (delta Pt) was partitioned into four components: arterial (delta Pa), pre-(delta Pa') and post-(delta Pv') capillary, and venous (delta Pv). The capillary filtration coefficient (Kf,c) was evaluated by measuring the amount of fluid filtering through the endothelium when arterial and venous pressures were suddenly increased. Capsaicin caused no changes in the vascular pressures at any level of the pulmonary circulation but induced a significant 3-fold increase in the Kf,c (P < 0.05). This reaction was accompanied by pulmonary oedema. The mechanisms involved in the permeability changes were investigated by testing the capacity of different drugs to block the response to capsaicin. Clonidine (10(-7) M to 10(-5) M), morphine (10(-6) M), aspirin (10(-3) M), ketanserin (10(-8) M) and (+/)- CP 96,345 (10(-6) M), an antagonist of neurokinin NK1 receptor, completely prevented the effects of capsaicin on the Kf,c. In contrast, terfenadine (10(-7)) together with cimetidine (10(-5) M) had no protective effect against capsaicin. It was concluded that capsaicin-induced pulmonary oedema was due to an increase in the capillary filtration coefficient and not to hemodynamic changes. This alteration in the endothelium permeability is mediated by the release of endogenous peptides from C-fibers upon the action of capsaicin and subsequent activation of NK1 receptors, probably by substance P. Moreover, 5-hydroxytryptamine receptors and arachidonic acid derivates are also involved in this reaction.
Delaunois
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A
Chaire de Pharmacologie-Pharmacothérapie-Toxicologie, Faculté de Médecine Vétérinaire, Université de Liège, Belgium.
Gustin
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P
Ansay
M
M
D000818:Animals; D002211:Capsaicin / Q000494:pharmacology*; D002463:Cell Membrane Permeability / Q000187:drug effects; D004730:Endothelium, Vascular / Q000187:drug effects*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D008168:Lung / Q000187:drug effects*; D008297:Male; D011652:Pulmonary Circulation / Q000187:drug effects*; D011817:Rabbits
D002211:Capsaicin