The research looked at the effects of high arginine and high lysine on the expression of transcriptional cardiometabolic indicators and nephrological hypertension markers in Wistar rats. Hypertensive Wistar rats were administered diets supplemented with two dietary amino acids, arginine and lysine. Biochemical indicators, as well as molecular indicators of vasodilator, nephrotoxic, and lipid-lowering, were studied. After 6 weeks of supplementing with high arginine (HA), the group's systolic blood pressure dropped by 25.0 mmHg. The effects of high arginine and high lysine treatment were measured using mRNA of vasodilator markers nephrotoxic markers, and lipid-lowering markers in Wistar rats. Our findings show that dietary supplementation with high arginine reduces nephrotoxicity and influences the metabolic pathways of cardiometabolic markers, hypercholesterolemia markers, and high lysine markers. Hypertension is the multifactorial ailment that affects over one billion individuals, cardiovascular disease, roughly one-third of world population, and chronic kidney disease (CKD) is an ignored medical basis of resistant hypertension with roughly 490 million CKD patients. In our present investigation, we hypothesise a profound effect of the dietary amino acids, arginine, and lysine, on hypertension, nephrotoxicity, and hypercholesterolemia. Hypercholesterolemia would result from an increase in lysine in the hepatic indicators of cholesterol, fatty acids, and TAG homeostasis. The high arg: lys ratio has a prominent influence in the effective regulation of the hypertension molecular markers in combating systolic blood pressure and controlling the hypercholesterolemia, and biomarkers of renal impairment recovery.