title: Lysophosphatidic acid alters cerebrovascular reactivity in piglets.
abstract: Effects of the lipid mediator lysophosphatidic acid (LPA) were studied on the cerebral circulation of newborn pigs using closed cranial windows. Topical application of synthetic LPA caused dose-dependent vasoconstriction and inhibited vasodilation to hypercapnia and isoproterenol. These vasodilators elicited a rise in the adenosine 3',5'-cyclic monophosphate (cAMP) content of the cerebrospinal fluid, which was inhibited dose dependently by LPA. Pertussis toxin (1 microgram/ml) completely abolished LPA-induced vasoconstriction and the altered vascular reactivity, and LPA no longer decreased cAMP. Electrophysiological recording of currents evoked by LPA-like lipids in Xenopus oocytes showed that cerebrospinal fluid is normally devoid of LPA-like factors. In contrast, the amount of LPA-like factors generated 4 days after intrathecal injection of autologous blood was in the range of 1-10 microM LPA equivalents. The data indicate that LPA-like bioactive mediators were generated in an intracranial hematoma model and that these phospholipids might play a role in the pathophysiology of altered vascular reactivity often found in posthemorrhagic conditions and could also contribute to the development of posthemorrhagic vasoconstriction.
authors.affiliation: Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
authors.forename: G
authors.initials: G
authors.lastname: Tigyi
authors.forename: L
authors.initials: L
authors.lastname: Hong
authors.forename: M
authors.initials: M
authors.lastname: Yakubu
authors.forename: H
authors.initials: H
authors.lastname: Parfenova
authors.forename: M
authors.initials: M
authors.lastname: Shibata
authors.forename: C W
authors.initials: CW
authors.lastname: Leffler
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D001160:Arterioles / Q000187:drug effects; D001790:Blood Physiological Phenomena; D001921:Brain / Q000378:metabolism; D002245:Carbon Dioxide / Q000494:pharmacology; D002560:Cerebrovascular Circulation / Q000187:drug effects*; D000242:Cyclic AMP / Q000134:cerebrospinal fluid; D007278:Injections, Spinal; D007545:Isoproterenol / Q000494:pharmacology; D008246:Lysophospholipids / Q000494:pharmacology*; D037342:Pertussis Toxin; D010841:Pia Mater / Q000098:blood supply; D013552:Swine; D014661:Vasoconstriction / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
chemical_list: D008246:Lysophospholipids; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D002245:Carbon Dioxide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007545:Isoproterenol