title: Endothelial-mediated dilations following severe controlled cortical impact injury in the rat middle cerebral artery.
abstract: The mechanisms associated with dysfunction of the cerebral vasculature following head trauma have not yet been fully elucidated. In an attempt to shed more light on the matter, we investigated the endothelial-mediated dilations in the rat middle cerebral artery (MCA) following severe traumatic brain injury (TBI). Rats were subjected to severe controlled cortical impact injury (CCI; 5 m/s, 130 ms duration, 3 mm deformation) over the right parietal cortex. At 24 h postinjury, ipsilateral segments of MCA and corresponding contralateral segments were isolated, mounted in a vessel chamber, and pressurized. The responses to 2 methylthio-ATP (2MeSATP), a selective agonist for the P2Y1 purinoceptors, N(omega)-nitro-L-arginine (L-NAME), an NO synthase inhibitor, and S-nitroso-N-acetylpenicillamine (SNAP), an exogenous NO donor, were determined. 2MeSATP elicited concentration dependent dilations in all MCAs studied. Ipsilateral MCAs harvested following TBI or sham-TBI, showed similar maximum dilations to 2MeSATP [70 +/- 4% (n = 17) and 72 +/- 6% (n = 13), respectively]. However, TBI reduced the concentration of 2MeSATP necessary to elicit one-half of the maximum dilation (EC50) from 15 to 9 nM (p < 0.05). Inhibition of NO synthase with 10(-5) M L-NAME abolished the dilation to 2MeSATP in both TBI and sham-TBI MCAs. The constriction to L-NAME was significantly reduced in TBI MCAs compared to sham vessels. Dilations to SNAP, an NO donor, were not altered by TBI indicating that the mechanisms of dilation involving NO in the vascular smooth muscle were not affected. Unlike other pathological conditions which often diminish endothelial-mediated responses, severe TBI enhanced the sensitivity to 2MeSATP without altering the maximum response.
authors.affiliation: Department of Neurosurgery, Baylor College of Medicine, Houston, Texas 77030, USA.
authors.forename: E M
authors.initials: EM
authors.lastname: Golding
authors.forename: M L
authors.initials: ML
authors.lastname: Steenberg
authors.forename: L
authors.initials: L
authors.lastname: Cherian
authors.forename: S P
authors.initials: SP
authors.lastname: Marrelli
authors.forename: C S
authors.initials: CS
authors.lastname: Robertson
authors.forename: R M
authors.initials: RM
authors.lastname: Bryan
mesh_terms: D000255:Adenosine Triphosphate / Q000031:analogs & derivatives; D000704:Analysis of Variance; D000818:Animals; D001930:Brain Injuries / Q000378:metabolism / Q000503:physiopathology*; D002536:Cerebral Arteries / Q000378:metabolism / Q000503:physiopathology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D004791:Enzyme Inhibitors; D016014:Linear Models; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000378:metabolism; D010396:Penicillamine / Q000031:analogs & derivatives; D051381:Rats; D020318:Rats, Long-Evans; D018048:Receptors, Purinergic P2 / Q000502:physiology; D013873:Thionucleotides; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D018048:Receptors, Purinergic P2; C110881:S-nitro-N-acetylpenicillamine; D013873:Thionucleotides; D009569:Nitric Oxide; D000255:Adenosine Triphosphate; D010396:Penicillamine; D019331:NG-Nitroarginine Methyl Ester; C008501:2-methylthio-ATP