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 r eceptors. The kynurenic acid content and kynurenine aminotransferase a ctivity was measured in micro-dissected regions of spontaneously hyper tensive rats (SHR) and their normotensive controls (Wistar-Kyoto rats: WKY). 2. Of the brain regions examined the highest kynurenine aminotr ansferase activity was found in the medulla followed by the olfactory bulb and the cerebellum, with the spinal cord showing the lowest activ ity. 3. All samples from SHR showed greatly reduced kynurenine aminotr ansferase activity compared to WKY. These reductions were most pronoun ced in the medulla and spinal cord, approximately 45-55%, and lowest i n the cerebellum and olfactory bulbs, approximately 25-30%. 4. The kyn urenic acid content of the rostral and caudal medulla as well as the s pinal cord was also significantly lower in SHR. 5. These results sugge st that there may be a deficiency in the kynurenic acid content and ky nurenine aminotransferase activity in the SHR. 6. Given the accumulati ng evidence of the importance of medullary glutamatergic pathways in t he control of blood pressure, as well as the higher sensitivity of car diovascular neurons of SHR to applied glutamate, it seems possible tha t endogenous kynurenic acid in the brain may play a role in the contro l of blood pressure and the pathogenesis of experimental hypertension in the SHR.