Objective: Although hypertension is a worldwide health problem, treatment options in low-income countries are still limited, resulting in high mortality. Therefore, the availability of drugs that are affordable and accessible to patients in low-income countries is still an urgent need. Since angiotensin II is one of the essential vasoconstrictive peptides in the human organism, we analyzed the impact of its posttranslational modification to pyruvamide-Ang II by pyridoxal-5’-phosphate on blood pressure. Pyridoxal-5’-phosphate is a less expensive vitamin B6 derivative and therefore could be a novel, cost-effective drug for the treatment of hypertension. Design and method: The post-translational modification of angiotensin II to pyruvamide-angiotensin II by pyridoxal-5’-phosphate was investigated in vitro by mass spectrometry. Calcium ion influx into vascular smooth muscle cells treated with angiotensin II or pyruvamide-angiotensin II, respectively, was also investigated in vitro. In ex vivo experiments, the vasoconstrictive effect of angiotensin II and pyruvamide-angiotensin II, respectively, was analyzed by using the bioassay of the isolated perfused rat kidneys. Furthermore, angiotensin II and pyruvamide-angiotensin II were investigated in in vivo experiments. Both Wistar Kyoto rats and spontaneously hypertensive rats were treated with pyridoxal-5’-phosphate by using mini-osmotic pumps and the blood pressure was measured time-dependently. Results: Calcium ion influx in vascular smooth muscle cells after stimulation with pyruvamide-angiotensin II was significantly decreased compared to angiotensin II. Perfusion pressure of isolated perfused rat kidney increased less by pyruvamide-angiotensin II than by angiotensin II. The systolic and diastolic blood pressure of spontaneously hypertensive rats treated with pyridoxal-5’-phosphate decreased from 171/139 ± 5 mmHg to 129/98 ± 2 mmHg after three days. The blood pressure of Wistar Kyoto rats treated with angiotensin II increased to 167/133 ± 3 mmHg, while the blood pressure of Wistar Kyoto rats treated with angiotensin II and pyridoxal-5’-phosphate decreased to 129/99 ± 2 mmHg. Conclusions: Pyridoxal-5’-phosphate significantly decreased rat blood pressure and might be a cost-effective drug for hypertension treatment. Respectively, an increased pyridoxal-5’-phosphate intake recommendation in the form of vitamin B6 intake might have a decreasing effect on blood pressure in the hypertensive population.