IDENTIFICATION OF ISATIN, AN ENDOGENOUS MAO INHIBITOR, IN THE BRAIN OF STROKE-PRONE SHR

We previously reported that stroke-prone spontaneously hypertensive ra ts (SHRSP) showed a significant increase in plasma norepinephrine (NE) concentration and a significant decrease in MAO activity compared wit h those of normotensive Wistar Kyoto rats (WKY). The systolic blood pr essure of SHRSP also correlated inversely with kidney MAO activity. Ga s chromatography mass spectrometry (GC-MS) has identified isatin as on e of the purified extracts of SHRSP urine which contains tribulin. In this study, purified extracts of SHRSP brain have also been identified as isatin by GC-MS. In order to elucidate the role of this endogenous MAO inhibitor, a study of the acute effects of isatin on rat brain NE and serotonin (5-HT) concentration was undertaken. A single dose of i satin significantly increased NE concentrations in the medulla oblonga ta, hippocampas, cerebellum, striatum and cortex of WKY. It also signi ficantly increased 5-HT concentrations and decreased 5-hydroxy indole acetic acid (5-HIAA) concentrations in WKY brains. The ratio of 5-HIAA /5-HT decreased significantly in both WKY and SHRSP brains. NE and 5-H T levels in the SHRSP brain after isatin did not differ from the contr ol. A single dose of isatin (50 mg/kg or 200 mg/kg, i.p.) did not incr ease the systolic blood pressure of WKY or SHRSP. These data suggest t hat isatin, an endogenous MAO inhibitor present in the SHRSP brain, pr olongs the life-span of NE and 5-HT and maintains high levels of monoa mines.