KYNURENIC ACID, AN ENDOGENOUS GLUTAMATE ANTAGONIST, IN SHR AND WKY RATS - POSSIBLE ROLE IN CENTRAL BLOOD-PRESSURE REGULATION

1. Kynurenine aminotransferase catalyzes the conversion of kynurenine to kynurenic acid, an endogenous antagonist of excitatory amino acid receptors. The kynurenic acid content and kynurenine aminotransferase activity was measured in micro-dissected regions of spontaneously hypertensive rats (SHR) and their normotensive controls (Wistar-Kyoto rats: WKY). 2. Of the brain regions examined the highest kynurenine aminotransferase activity was found in the medulla followed by the olfactory bulb and the cerebellum, with the spinal cord showing the lowest activity. 3. All samples from SHR showed greatly reduced kynurenine aminotransferase activity compared to WKY. These reductions were most pronounced in the medulla and spinal cord, approximately 45-55%, and lowest in the cerebellum and olfactory bulbs, approximately 25-30%. 4. The kynurenic acid content of the rostral and caudal medulla as well as the spinal cord was also significantly lower in SHR. 5. These results suggest that there may be a deficiency in the kynurenic acid content and kynurenine aminotransferase activity in the SHR. 6. Given the accumulating evidence of the importance of medullary glutamatergic pathways in the control of blood pressure, as well as the higher sensitivity of cardiovascular neurons of SHR to applied glutamate, it seems possible that endogenous kynurenic acid in the brain may play a role in the control of blood pressure and the pathogenesis of experimental hypertension in the SHR.