Therapeutic effects of L‐lysine in Dahl SS rats, a Model of Salt‐Induced Hypertension

Our previous studies have suggested that dual treatment of glomerular filtration and albumin reabsorption might be an effective approach to treating salt-sensitive (SS) hypertension. L-lysine, an essential amino acid for humans, has been shown to inhibit tubular protein reabsorption with rapidly increasing urinary albumin excretion in healthy male participants. Our recent metabolomics study revealed that intrarenal levels of L-Lysine are reduced in Dahl SS rats when animals are fed a high salt diet. In our initial experiments, we tested the effects of L-lysine during the development of hypertension. We found that L-lysine administration (17 mg/ml drinking water supplement) in SS rats restores albumin balance, triggers diuresis, and diminishes the development of SS hypertension. In our following experiments, we utilized a therapeutic approach to testing the hypothesis that L-lysine could decrease the blood pressure of subjects with developed hypertension. The SS rats were initially kept on a 0.4% NaCl diet. When they reached 8-weeks in age, rats were challenged with an 8% NaCl high salt diet (HS) for 10 days until they exceeded an average mean arterial pressure (MAP) of 140 mmHg (N=13; MAP was measured by implanted telemetry). Then, rats were randomly assigned to treatment and control groups. After another 11 days, all rats were euthanized and tissue was collected for further analyses. At the endpoint, the hypertensive L-lysine treated rats had significantly lower MAP than hypertensive vehicle-treated rats (145±5 mmHg vs. 176±8 mmHg). Interestingly, therapy with L-lysine treatment did not result in a significant difference in diuresis or albuminuria. Excretion for all major electrolytes was comparable between the two groups except for Cl- (Cl- /Creatinine for vehicle vs treated: 142±8 & 209±19). Increased excretion in Cl- is most likely due to the administration of L-lysine as a chloride salt. Preliminary analysis using immunohistochemistry suggests less kidney damage in the treatment group compared to the vehicle group. Therefore, our data propose that L-lysine, when used as a therapeutic, can effectively treat SS hypertension.