ENDOTHELIAL-MEDIATED DILATIONS FOLLOWING SEVERE CONTROLLED CORTICAL IMPACT INJURY IN THE RAT MIDDLE CEREBRAL-ARTERY

The mechanisms associated with dysfunction of the cerebral vasculature following head trauma have not yet been fully elucidated. In an attem pt to shed more light on the matter, we investigated the endothelial-m ediated dilations in the rat middle cerebral artery (MCA) following se vere traumatic brain injury (TBI). Rats were subjected to severe contr olled cortical impact injury (CCI; 5 m/s, 130 ms duration, 3 mm deform ation) over the right parietal cortex. At 24 h postinjury, ipsilateral segments of MCA and corresponding contralateral segments were isolate d, mounted in a vessel chamber, and pressurized. The responses to 2 me thylthio-ATP (2MeSATP), a selective agonist for the P2Y(1) purinocepto rs, NW-nitro-L-arginine (L-NAME), an NO synthase inhibitor, and S-nitr oso-N-acetylpenicillamine (SNAP), an exogenous NO donor,were determine d. 2MeSATP elicited concentration dependent dilations in all MCAs stud ied. Ipsilateral MCAs harvested following TBI or sham-TBI, showed simi lar maximum dilations to 2MeSATP [70 +/- 4% (n = 17) and 72 +/- 6% (n = 13), respectively]. However, TBI reduced the concentration of 2MeSAT P 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 abo lished the dilation to 2MeSATP in both TBI and sham-TBI MCAs. The cons triction to L-NAME was significantly reduced in TBI MCAs compared to s ham vessels. Dilations to SNAP, an NO donor, were not altered by TBI i ndicating 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 enhan ced the sensitivity to 2MeSATP without altering the maximum response.