[en] 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
Disciplines :
Veterinary medicine & animal health
Author, co-author :
Delaunois, Annie ; Université de Liège - ULiège > Relations académiques et scientifiques (Méd. vétérinaire)
Gustin, Pascal ; Université de Liège - ULiège > Département de sciences fonctionnelles > Pharmacologie, pharmacothérapie et toxicologie
Ansay, Michel ; Université de Liège - ULiège > Faculté de médecine vétérinaire
Language :
English
Title :
Effects of Capsaicin on the Endothelial Permeability in Isolated and Perfused Rabbit Lungs
Alving K. (1991) Airways vasodilatation in the immediate allergic reaction: involvement of inflammatory mediators and sensory nerves. Acta Physiol Scand 141:64.
Barnes PJ (1987) Neuropeptides in human airways: function and clinical implications. Am Rev Respir Dis 136:S77.
Birch PJ, Harrisson SM, Hayes AG, Rogers H., Tyers MB (1992) The non‐peptide NK1 receptor antagonist, (±)CP 96345, produces antinociceptive and anti‐oedema effects in the rat. Br J Pharmacol 105:508-510.
Black J., Diment L., Armour C., Alouan L., Johnson P. (1990) Distribution of substance P receptors in rabbit airways, functional and autoradiographic studies. J Pharmacol Exp Ther 253:381-386.
Black J., Diment L., Alouan L., Johnson P., Armour C., Badgery‐Parker T., Burcher E. (1992) Tachykinin receptors in rabbit airways‐characterization by functional, autoradiographic and binding studies. Br J Pharmacol 107:429-436.
Brown DR (1987) Intracellular mediators of peptide action in the intestine and airways: focus on ion transport function. Am Rev Respir Dis 130:S43.
Dawson CA, Linehan JH, Rickaby DA (1982) Pulmonary microcirculatory hemodynamics. Ann NY Acad Sci 384:90-106.
Delaunois A., Gustin P., Ansay M. (1992) Altered capillary filtration coefficient in parathion‐ and paraoxon‐ induced pulmonary edema in isolated and perfused rabbit lungs. Toxicol Appl Pharmacol 116:161-169.
Delaunois A., Gustin P., Ansay M. (1992) Role of neuropeptides in acetylcholine‐induced edema in isolated and perfused rabbit lungs. J Pharmacol Exp Ther.
Drake RE, Gabel JC (1981) Comparison of techniques to measure pulmonary capillary filtration coefficient in dogs. Microv Res 21:133-141.
Ennis M., Lorenz W., Gerland W., Heise J. (1987) Isolation of mast cells from rabbit lung and liver: comparison of histamine release induced by the hypnotics althesin and propanidid. Agents Actions 20:219-222.
Gibbins IL, Furness JB, Costa M., MacEntyre I., Hillyard CJ, Girgis S. (1985) Co‐localization of calcitonin gene‐related peptide‐like immunoreactivity with substance P in cutaneous, vascular and visceral sensory neurons in guinea pigs. Neurosci Lett 57:125-130.
Gitter BD, Waters DC, Bruns RF, Mason NR, Nixon JA, Howbert JJ (1991) Species differences in affinities of non‐peptide antagonists for substance P receptors. Eur J Pharmacol 197:237-238.
Gustin P., Urbain B., Delaunois A., Zeimes K., Ansay M. (1992) Permeability of the endothelium and partitioning of the pulmonary blood flow resistance in isolated and perfused pig lungs: effects of breed and age. Vet Res Commun 16:69-82.
Hägermark Ö, Hökfelt T., Pernow B. (1978) Flare and itch induced by substance P in human skin. Journal of Investigative Dermatology 71:233-235.
Hakim TS (1988) Identification of constriction in large versus small vessels using the arterial‐venous and double‐occlusion techniques in isolated canine lungs. Respiration 54:61-69.
Hakim TS, Michel RP, Chang HK (1982) Partitioning of pulmonary vascular resistance in dogs by arterial and venous occlusion. J Appl Physiol 52:710-715.
Hua XY, Lundberg JM, Theodorsson‐Norheim E., Brodin E. (1985) Comparison of cardiovascular and bronchoconstrictor effects of substance P, substance K and tachykinins. Naunyn Schmiedebergs Arch Pharmacol 328:196-201.
Jancso N., Jancso‐Gabor A., Szolcsanyi J. (1967) Direct evidence for neurogenic inflammation and its prevention by denervation and pretreatment with capsaicin. Br J Pharmacol 31:138-151.
Johnson AR, Erdös EG (1973) Release of histamine from mast cells by vasoactive peptides. Proc Soc Exp Biol Med 142:1252-1256.
Joos GFP, Rar, Van Der Srtaeten (1988) The role of neuropeptides as neurotransmitters of non‐adrenergic, non‐cholinergic nerves in bronchial asthma. Bull Eur Physiopathol Res 23:619-637.
Kern DF, Kivlen C., Malik AG (1984) Pulmonary capillary filtration coefficient (Kf,c): blood vs Albumin‐Ringer's. Microv Res 27:248.
Laitinen LA, Laitinen A., Panula PA, Partanen M., Tervo K., Tervo T. (1983) Immunohistochemical demonstration of substance P in the lower respiratory tract of the rabbit and not of man. Thorax 38:531-536.
Laitinen LA, Laitinen A., Salonen RO, Widdicombe JG (1987) Vascular actions of airway neuropeptides. Am Rev Respir Dis 136:S59.
Lundberg JM, Saria A. (1982) Capsaicin sensitive vagal neurons involved in control of vascular permeability in rat trachea. Acta Physiol Scand 115:521-523.
Lundberg JM, Saria A. (1983) Capsaicin induced desensitization of the airway mucosa to cigarette smoke, mechanical and chemical irritants. Nature 302:251-253.
Lundberg JM, Martling CR, Saria A., Folkers K., Rosell S. (1983) Cigarette smoke induced oedema due to activation of capsaicin‐sensitive vagal afferents and substance P release. Neurosci 10:1361-1368.
Lundberg JM, Saria A., Abrodin E., Rosell S., Fokers K. (1983) A substance P antagonist inhibits vagally induced increase in vascular permeability and bronchial smooth muscle contraction in the guinea pig. Proc Natl Acad Sci USA 80:1120-1124.
Lundberg JM, Fahrenkrug J., Hokfelt T., Martling CR, Larsson O., Tatemoto K., Anggard A. (1984) Coexistence of peptide HI (PHI) and VIP in nerves regulating blood flow and bronchial smooth muscle tone in various mammals including man. Peptides 235:593-606.
Lundberg JM (1990) Peptide and classical transmitter mechanisms in the autonomic nervous system. Arch Int Pharmacodyn 303:9-19.
Menconi M., Hahn G., Polgar P. (1984) Prostanoids synthesis by cells comprising the calf pulmonary artery. J Cell Physiol 120:163-168.
Mizoguchi H., Bergeron ML (1991) Effect of capsaicin on nasal secretion in anesthetized ferrets. J Appl Physiol 70:282-286.
Mizrahi J., D'Orléans‐Juste P., Caranikas S., Regoli D. (1982) Pharmacological effects of peptides in the tracheal smooth muscle. Pharmacology 25:39-50.
Naline E., Devillier P., Drapeau G., Toty L., Bakdach H., Regoli D., Advenier C. (1989) Characterization of neurokinin effects and receptor selectivity in human isolated bronchi. Am Rev Respir Dis 140:679-686.
Ollerenshaw S., Jarvis D., Woolcock A., Sullivan C., Scheibner T. (1989) Absence of immunoreactive intestinal polypeptide in tissue from the lungs of patients with asthma. N Engl J Med 320:1244-1248.
Regoli D., Escher R., Mizrahi J. (1984) Substance P: structure‐activity studies and the development of antagonists. Pharmacologist 28:301-320.
Regoli D., Drapeau G., Dion S., D'Orléans‐Juste P. (1987) Pharmacological receptors for substance P and neurokinins. Life Sci 40:109-117.
Regoli D., Dion S., Rhaleb NE, Drapeau G., D'Orléans‐Juste P. (1990) Vasoactive peptides and their receptors. Blood Vessels 27:137-145.
Saria A., Theodorsson‐Norheim E., Gamse R., Lundberg JM (1984) Release of substance P and substance K‐like immunoreactivities from the isolated perfused guinea‐pig lung. Eur J Pharmacol 106:207-208.
Seeger W., Menger M., Walmrath D., Becker G., Grimmenger F., Neuhof M. (1987) Arachidonic acid lipoxygenase pathways and increased vascular permeability in isolated rabbit lungs. Am Rev Respir Dis 136:964-972.
Snider RM, Constantine JW, Lowe JA, Longo KP, Lebel WS, Woody HA, Drozda SE, Desai MC, Vinick FJ, Spencer RW, Hess HJ (1991) A potent nonpeptide antagonist of the substance P (NK1) receptor. Science 251:435-437.
Sumita T., Ishikawa N., Nashiba Y., Takagi K., Satake T. (1989) 5‐Hydroxytryptamine receptor subtypes participating in pulmonary edema in dogs. Eur J Pharmacol 164:69-75.
Wangensteen OD, Lysaker E., Davaryn P. (1977) Pulmonary capillary filtration and flexion coefficients in the adult rabbit. Microvascular Research , 81, 37; 14.
Wharton J., Polak JM, Bloom SR, Will JA, Brown MR, Pearse (1979) Substance P‐like immunoreactive nerves in mammalian lung. Invest Cell Pathol 2:3-10.
Whorten GS, Gumbay RS, Tanaka DT, Grunstein MM (1985) Opposing hemodynamic effects of substance P on pulmonary vasculature in rabbits. J Appl Physiol 59:1098-1103.