Abstract

Abstract Background/Introduction Hypertension is a worldwide health problem and treatment options in low-income countries are still limited. This results in high mortality. Therefore, the availability of drugs that are affordable and accessible to patients in low-income countries is still an urgent need. Angiotensin II, one of the essential vasoconstrictive peptides in the human organism, is post-translationally modified to pyruvamide-angiotensin II by pyridoxal-5’-phosphate. Pyridoxal-5’-phosphate is a less expensive vitamin B6 derivative and therefore could be a novel, cost-effective drug for the treatment of hypertension. Purpose We analysed the impact of post-translational modification of angiotensin II to pyruvamide-angiotensin II by pyridoxal-5’-phosphate on blood pressure. Methods 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 analysed 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 lower compared to angiotensin II. Perfusion pressure of isolated perfused rat kidney increased less by pyruvamide-angiotensin II than by angiotensin II. Furthermore, the systolic and diastolic blood pressure of SHR treated with PLP decreased to physiological levels after three days of treatment (syst./diast.: 171 ± 1 / 139 ± 5 mmHg vs. 129 ± 1 / 98 ± 2 mmHg; p<0.0001). The blood pressure of WKY rats treated with Ang II increased to hypertensive values after three days of treatment, while the blood pressure of WKY rats treated with Ang II and PLP is within the physiological range (syst./diast.: 167 ± 1 / 133 ± 3 mmHg vs. 129 ± 1 / 99 ± 2 mmHg; p<0.0001). 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.