A DIFFERENTIAL RESPONSE OF DIFFUSE BRAIN INJURY ON THE CONCENTRATIONSOF ENDOTHELIN AND NITRIC-OXIDE IN THE PLASMA AND BRAIN-REGIONS IN RATS

In the present study, we hypothesized that acute diffuse brain injury (DBI) in rats would produce an increase in endothelin-1 (ET-1), a pote nt vasoconstrictor, and/or nitric oxide (NO), a potent vasodilator, in plasma and brain areas in rats. DBI was induced in anesthetized male Sprague-Dawley rats (350-400 g) using a 350 g weight dropped from 1 me ter height impact through a device designed by Marmarou et at., 1994. Blood plasma and brain tissue (cerebral cortex, diencephalon and brain stem) samples were collected for estimation of ET-1 and NO at zero or 6 h from rats (n = 6) subjected to DBI as well as control rats (n = 6 ), i.e., not subjected to DBI. In a separate group of animals, cerebra l blood flow (CBF) was recorded at 0, 5, 10, 15, 30, 60, 120, 240 and 360 min after induction of DBI or sham-DBI. Acute DBI produced a signi ficant decrease in CBF at 120 min after induction of DBI. Plasma level s of ET-1 was found to be significantly increased (from 0.89 +/- 0.09 to 2.09 +/- 0.29 pg ml(-1)), at 6 h following DBI. DBI produced a sign ificant decrease in the levels of ET-1 in diencephalon (from 70.97 +/- 9.47 to 51.64 +/- 2.65 pg g(-1)). In contrast to ET-1, DBI produced a significant increase in the concentrations of NO in the diencephalon, cerebral cortex and brain stem at 6 h Post DBI. II appears that DBI-i nduced increase in the levels of NO in brain regions Which might De do wn regulating the synthesis of ET-1 in diencephalon. It is concluded t hat ET and NO homeostatic mechanisms may play a role in the regional a nd vascular responses associated with acute DBI.