Xenopsin, neurotensin, neurotensin(8-13) and N-acetyl-neurotensin(8-13) inhibit vascular leakage in rats after tissue injury.
Swelling, edema and leakage of proteins from the vascular compartment are immediate inflammatory responses of living tissues to local injury. Xenopsin, neurotensin (NT), NT(8-13) and NAcNT(8-13) administered to male rats anesthetized with sodium pentobarbital 60 mg/kg i.p. inhibited swelling and edema in the paw induced by immersion in 58 degrees water for 1 min. The ED50 values for xenopsin. NT, NAcNT(8-13) and NT(8-13) for reducing heat-induced edema were 0.9, 1.5, 1.9 and 2.1 nmol/kg i.v., respectively. NAcNT(8-13) was chosen as a prototype for further studies because, compared to NT, it had minimal hypotensive effects. NAcNT(8-13), 4 nmol/kg i.v., injected 10 min before mechanical injury to muscle, produced by a 4 cm midline surgical incision in the rectus abdominis, or before freeze injury to the cortex, produced by applying a cold probe (-50 degrees C) to the skull for 4 min, reduced vascular leakage, measured as area of Monastral blue staining of the injured tissues. NAcNT(8-13), 4 nmol/kg i.v., also attenuated pulmonary edema induced by epinephrine bitartrate 10 micrograms/kg i.v. The ability of NAcNT(8-13) to inhibit vascular leakage was not linked to its transient hypotensive effects and it was not blocked by alpha-helical-CRF(9-41), a putative CRF receptor antagonist, or by chlorpheniramine, a H1-histamine receptor antagonist.
School of Public Health, University of California, Berkeley.
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D000818:Animals; D001929:Brain Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D002199:Capillary Permeability / Q000187:drug effects*; D004487:Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D006358:Hot Temperature; D008297:Male; D009132:Muscles / Q000473:pathology; D009496:Neurotensin / Q000031:analogs & derivatives* / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D010455:Peptides; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control; D051381:Rats; D017207:Rats, Sprague-Dawley; D029867:Xenopus Proteins
D009842:Oligopeptides; D010446:Peptide Fragments; D010455:Peptides; D029867:Xenopus Proteins; D009496:Neurotensin; C016832:xenopsin; C054381:neurotensin (8-13); C034659:acetylneurotensin (8-13)