title: The involvement of sympathetic nerves in plasma extravasation induced by prostaglandin E2 and substance P.
abstract: The effects of intravenous injection of prostaglandin E2 (PGE2), substance P (SP) and a metabolically stable SP analogue, [pGlu5,Me-Phe8,Sar9]-SP (5-11) on plasma extravasation of albumin in the rat after blockade of prostaglandin synthesis with indomethacin or chemical sympathectomy with guanethidine were studied. Blood pressure was decreased by all agonists, but only the hypotensive effects of SP were enhanced by pretreatment with indomethacin and guanethidine. The increase in plasma extravasation induced by PGE2 in the tongue, skin and lungs was blocked by both guanethidine and indomethacin. Pretreatment of the rats with guanethidine or indomethacin increased extravasation induced by SP in the tongue-tip, dorsal skin and foot, but decreased the enhanced permeability in the pinna, and did not alter the actions of the peptide in other tissues. In contrast, both guanethidine and indomethacin pretreatment increased vascular permeability responses to [pGlu5,Me-Phe8,Sar9]-SP (5-11) administration in 9 and 14 of 16 tissues examined, respectively. Thus, intact sympathetic nerves and functional cycloxygenase activity exert inhibitory constraints on the vascular permeability effects of intravenously administered SP or its analogue. On the other hand the integrity of the sympathetic nerves and prostaglandin synthesis are required for PGE2-induced increases in vascular leak.
authors.affiliation: Department of Medical Physiology, Faculty of Medicine, University of Calgary, Alberta, Canada.
authors.forename: R
authors.initials: R
authors.lastname: Mathison
authors.forename: J S
authors.initials: JS
authors.lastname: Davison
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002199:Capillary Permeability / Q000187:drug effects*; D015232:Dinoprostone / Q000494:pharmacology*; D006145:Guanethidine / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D008297:Male; D008969:Molecular Sequence Data; D009638:Norepinephrine / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000031:analogs & derivatives; D051381:Rats; D017207:Rats, Sprague-Dawley; D013373:Substance P / Q000031:analogs & derivatives / Q000494:pharmacology*; D013564:Sympathetic Nervous System / Q000502:physiology*
chemical_list: D010446:Peptide Fragments; D013373:Substance P; C032720:substance P (5-11), pGlu(5)-MePhe(8)-MeGly(9)-; D015232:Dinoprostone; D011761:Pyrrolidonecarboxylic Acid; D009638:Norepinephrine; D007213:Indomethacin; D006145:Guanethidine