Altered NO function contributes to impairment of uPA and tPA cerebrovasodilation after brain injury.


:Urokinase (uPA) and tissue plasminogen activator (tPA) are serine proteases implicated in fibrinolysis, but their role in the regulation of the cerebrovascular response to brain trauma has not been investigated. This study was designed to (1) characterize the cerebrovascular activity of uPA and tPA, (2) investigate the role of nitric oxide (NO) in uPA and tPA vascular activity, and (3) characterize the effect of fluid percussion brain injury (FPI) on vascular responses to uPA and tPA. The closed cranial window technique in chloralose anesthetized newborn pigs was used to measure pial artery diameter and collect CSF for radioimmunoassay (RIA) of cGMP concentration. Topical uPA (10(-9), 10(-7) M) elicited pial artery dilation that was blunted by the NO synthase inhibitor, L-NNA (10(-6) M) (8 +/- 1% and 13 +/- 1 vs. 3 +/- 1% and 7 +/- 2%, respectively). Vasodilation in response to uPA was associated with an increase in CSF cGMP concentration (645 +/- 20, 865 +/- 39 and 1088 +/- 33 fmol/mL cGMP for control, uPA 10(-9), 10(-7) M, respectively). Similar data were obtained for tPA. Pial artery dilation to uPA was blunted following FPI (7 +/- 1% and 12 +/- 1% vs. 3 +/- 1% and 6 +/- 1%, respectively), while uPA-associated release of cGMP was blocked (677 +/- 45, 909 +/- 53, and 1110 +/- 55 vs. 283 +/- 10, 316 +/- 18, and 333 +/- 26 fmol/mL for control, uPA 10(-9), 10(-7) M before and after FPI, respectively). Similar data were obtained for tPA. These data show that uPA and tPA produce pial artery dilation in an NO-dependent manner. FPI blunted uPA and tPA induced pial artery dilation as well as the associated release of cGMP. These data suggest therefore that altered NO function contributes to the impairment of uPA and tPA cerebrovasodilation after brain injury.


J Neurotrauma


Journal of neurotrauma


Armstead WM,Cines DB,Al-Roof Higazi A




Has Abstract


2004-09-01 00:00:00












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