Abstract 978 Post-translational modification of angiotensin II by vitamin B6 for hypertension treatment in low-income countries

Clin Res Cardiol (2023). https://doi.org/10.1007/s00392-023-02180-w
Post-translational modification of angiotensin II by vitamin B6 for hypertension treatment in low-income countries
M. Lellig¹, J. Muñoz-Castañeda², J. Hermann¹, H. Noels¹, M. Rodríguez², J. Jankowski¹, V. Jankowski¹
¹Institut für Molekulare Herz-Kreislaufforschung (IMCAR), Uniklinik RWTH Aachen, Aachen; ²Instituto Maimonides para la Investigacion Biomedica (IMIBIC), Cordoba, ES;
Introduction: Hypertension is a worldwide health problem, but in low-income countries the treatment options are limited. Therefore, finding a drug that is affordable and accessible to patients in these low-income countries is an urgent need. Angiotensin II (Ang II), the main component of the renin-angiotensin-aldosterone-system (RAAS), is one of the best-known vasoconstrictive peptides in the human organism. Recent data demonstrate that Ang II is post-translationally modified to pyruvamide-angiotensin II (Ang P) by pyridoxal-5’-phosphate, a less expensive vitamin B₆ derivative. In this study, the effect of pyridoxal-5’-phosphate and modified Ang II on blood pressure was analyzed in-vivo, ex-vivo and in-vivo. Methods: The influx of calcium ions into vascular smooth muscle cells (VSMC) in the presence and absence of Ang II and Ang P, respectively, was investigated in-vitro. In ex vivo experiments, the vasoconstrictive effect of Ang II and Ang P, respectively, was analyzed by using a bioassay of an isolated perfused rat kidney. Furthermore, Ang II and Ang P were investigated in in vivo experiments to validate the impact of Ang P. Both Wistar Kyoto rats (WKY) and spontaneously hypertensive rats (SHR) were treated with Ang II in the absence and presence of pyridoxal-5’-phosphate. Blood pressure was measured time-dependently. Results: Calcium influx in VSMC after stimulation with Ang P was significantly decreased compared with the effect of Ang II. Perfusion pressure of the isolated perfused rat kidney increased by 50.11 ± 4.57 mmHg by Ang II, while perfusion pressure increased by only 8.40 ± 4.31 mmHg by Ang P. The systolic and diastolic blood pressure of SHR treated with pyridoxal-5’-phosphate decreased from 171/139 ± 5 mmHg to 129/98 ± 2 mmHg after three days. The blood pressure of WKY treated with Ang II increased to 167/133 ± 3 mmHg, while the blood pressure of WKY treated with Ang II and pyridoxal-5’-phosphate decreased to 129/99 ± 2 mmHg. Conclusions: Pyridoxal-5’-phosphate significantly decreased blood pressure in SHR and WKY and might be a less expensive drug alternative and cost-effective drug against hypertension. Respectively, a recommendation for an increased nutritional vitamin B₆ intake might have a decreasing effect on blood pressure in the hypertensive population.
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