substance-p--arg(1)-pro(2)-trp(7)-(9)-leunh(2)(11)- and Edema

Topics: Animals; Cimetidine; Edema; Electric Stimulation; Hot Temperature; Male; Nerve Fibers; Peptide Fragments; Pyrilamine; Rats; Skin; Substance P

Immersion of the hind paws of anesthetized rats in hot water for 5 min induced massive plasma protein leakage as indicated by extravasation of Evans blue dye in the skin. The threshold temperature which caused noticeable plasma extravasation was 45 degrees C, a maximal response was obtained between 55 degrees C and 60 degrees C. Pretreatment of rats 2 days after birth with 50 mg kg-1 capsaicin significantly reduced the Evans blue extravasation induced by hot water at 50 degrees C and 60 degrees C, whereas guanethidine pretreatment 24 h before the experiment caused a significantly increased response at 40 degrees C, 45 degrees C and 50 degrees C. When Evans blue was injected between 10 and 120 min after immersion of the paw in hot water, a significant extravasation of the dye was no longer detectable. However, the weight of the paw as well as the weight of the piece of skin taken for Evans blue quantification increased during this period indicating the progressive development of oedema in the skin and underlying tissues. In rats treated with capsaicin as neonates, the increase in paw weight after immersion in water of 50 degrees C for 5 min was significantly delayed during the first hour, but there was no difference after two hours. In rats pretreated with D-Arg1,D-Pro2-,D- Trp7 ,9, Leu11 -substance P, a substance P (SP) antagonist, the Evans blue extravasation was significantly reduced. However, the response, which remained in rats treated with capsaicin as neonates was not blocked by the SP-antagonist. 6 It is concluded that activation of peripheral branches of sensory SP neurones contributes to the initial massive protein extravasation and to the subsequent rate of development of oedema following heat injury. Release of histamine did not significantly contribute to this response at the lower temperatures, although the response was reduced by histamine receptor blocking drugs at 55 degrees and 60 degrees C. Decreasing the sympathetic vasoconstrictor tone by guanethidine resulted in an increased response.

Topics: Animals; Blood Proteins; Burns; Capsaicin; Edema; Evans Blue; Female; Hindlimb; Male; Nerve Tissue Proteins; Neurons, Afferent; Rats; Rats, Inbred Strains; Substance P; Temperature; Time Factors

The effect of cigarette smoke on vascular permeability in the rat nasal mucosa was studied using the Evans blue extravasation method. Exposure to smoke from cigarettes induced a significant extravasation of Evans blue in the nasal mucosa of normal rats, suggesting an increased vascular permeability to plasma proteins. The oedema response was correlated to tar, nicotine and vapour phase components in the smoke. The smoke-induced permeability effect was abolished in rats pretreated neonatally with capsaicin. Also, systemic or local pretreatment with [D-Arg, D-Pro, D-Trp, Leu]Substance P, a substance P antagonist, inhibited the permeability response to cigarette smoke. Insertion of a glass-fibre filter, which removes the particulate phase of the smoke (including nicotine), did not significantly reduce the permeability response. The present findings suggest that the smoke-induced oedema in the rat nasal mucosa is not caused by nicotine but by vapour-phase irritants, which activate capsaicin-sensitive C-fibre afferents. These neurons then release agents such as substance P or a related tachykinin which increase permeability to plasma proteins.

Topics: Animals; Blood Pressure; Capillary Permeability; Capsaicin; Carbon Monoxide; Edema; Histamine Antagonists; Male; Nasal Mucosa; Nicotine; Rats; Rats, Inbred Strains; Smoking; Substance P

Exposure of rats to smoke from one cigarette caused local oedema due to a marked increased in vascular permeability from the epiglottis down to bronchioli, as indicated by extravasation of Evans blue in the airway mucosa. The cigarette smoke-induced extravasation of Evans blue was still present after removal of the tar and nicotine content of the smoke, suggesting that chemical irritants in the vapour phase were the main mediators of the vascular permeability response. Local or systemic pretreatment with capsaicin or [D-Arg1, D-Pro2, D-Trp7,9, Leu11] SP, a substance P antagonist, abolished or significantly reduced the airway oedema induced by cigarette smoke or vagal nerve stimulation. No reduction of the cigarette smoke or vagally induced tracheal oedema was seen upon pretreatment with mepyramine plus cimetidine, fentanyl, disodiumchromoglycate, methylprednisolone or terbutaline. The results thus indicate that the cigarette smoke or vagally induced tracheal oedema is most likely to be due to substance P release from local capsaicin-sensitive afferent neurons in the airway mucosa. Local administration of substance P antagonists may be considered as a pharmacological means of inhibiting local mucosal oedema in the airways caused by airway irritants such as cigarette smoke.

Topics: Afferent Pathways; Animals; Capillary Permeability; Capsaicin; Edema; Male; Microscopy, Fluorescence; Rats; Rats, Inbred Strains; Respiratory System; Respiratory Tract Diseases; Smoking; Substance P; Synaptic Transmission; Vagus Nerve