Lysophosphatidic acid alters cerebrovascular reactivity in piglets.
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.
Tigyi
G
G
Department of Physiology and Biophysics, University of Tennessee, Memphis 38163, USA.
Hong
L
L
Yakubu
M
M
Parfenova
H
H
Shibata
M
M
Leffler
C W
CW
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
D008246:Lysophospholipids; D014665:Vasodilator Agents; D010566:Virulence Factors, Bordetella; D002245:Carbon Dioxide; D000242:Cyclic AMP; D037342:Pertussis Toxin; D007545:Isoproterenol