Abstract:OBJECTIVE To investigate the characteristics of Chinese medicine syndromes and possible metabolic substance basis of spontaneously hypertensive rat (SHR), a common model animal for hypertensive research. METHODS The general state, temperament, peripheral vascular filling, tongue image, diet and water intake, urine and feces volume and characteristics, blood pressure, heart rate, respiratory rate, pain threshold and open field of SHR rats were observed and tested comprehensively to identify the possible syndrome types of Chinese medicine. At the same time, Liquid Chromatography Tandem mass Spectrometry (LC-MS/MS) was used to analyze non-targeted serum metabolites, so as to preliminarily reveal the material basis of blood pressure elevation and Chinese medicine syndrome manifestations. RESULTS Compared with WKY group, SHR was dark yellow, irritable state and peripheral capillary filling score were significantly increased (P≤0.05); Red tongue color, dry tongue, little body fluid; Quantity of feces, urine, diet and drinking water decreased significantly, and the water content of feces was low (P≤0.05); Systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), heart rate (HR) and respiratory rate (RR) were significantly increased(P≤0.05); Pain threshold decreased(P≤0.05); The open field experiment showed that the moving distance and residence time of the edge increased (P≤0.05). Serum non-targeted metabolomics results showed that compared with WKY group, there were 114 metabolites with significant differences in SHR (P≤0.05). These differential metabolites were mainly Lipids and lips-like molecules (40.35%), Organic acids and derivatives (22.8%), and Organoheterocyclic compounds (15.79%). A total of 25 metabolic pathways were obtained by KEGG enrichment analysis. Further differential abundance analysis showed that 16 pathways were activated, only 4 pathways were inhibited, and 5 pathways were not significantly changed. The Glutamatergic Synapse (Glutamatergic Synapse) and gamma-aminobutyric acid Synapse (GABAergic Synapse) were activated, while the 5-serotonergic synapse (Serotonergic synapse) was inhibited. CONCLUSION The symptoms of SHR include impatience and irritability, peripheral vascular dilation and collateral circulation formation, bulbar conjunctival congestive swelling, red tongue color, dry tongue, constipation, red yellow urine with little urine, rapid heart rate and respiratory rate, etc. All these suggest that SHR is a syndrome of hypertension with hyperactivity of liver-yang. The material basis of SHR is not only related to lipid and amino acid and carbohydrate metabolism disorders, but also may be related to the activation of excitatory neurometabolic pathway and inhibition of inhibitory neurometabolic pathway.