Pyridoxal‐5′‐phosphate: A cost‐effective treatment candidate for hypertensive patients?
Copyright policy )Pyridoxal‐5′‐phosphate: A cost‐effective treatment candidate for hypertensive patients?
AbstractObjectivesBecause angiotensin (Ang) II is an essential vasoconstrictive peptide, we analyzed the impact of its post‐translational modification to pyruvamide–Ang II (Ang P) by pyridoxal‐5′‐phosphate (PLP) on blood pressure. PLP is a less expensive vitamin B6 derivative and, therefore, could be a cost‐effective drug against hypertension.MethodsEffect of Ang P on calcium ion entry into vascular smooth muscle cells (VSMCs) was analyzed. Binding affinity of Ang P to angiotensin II type 1 receptor (AT1R) was measured. Vasoconstrictive effect of Ang P was investigated using the bioassay of isolated perfused rat kidneys. Spontaneously hypertensive rats (SHR) were administered PLP. Additionally, Wistar Kyoto rats (WKY) received Ang II and PLP. Blood pressure was measured time‐dependently.ResultsAng II, incubated with PLP, was post‐translationally modified to Ang P. Calcium ion entry in VSMCs was significantly lower with Ang P compared to Ang II. Binding affinity of Ang P to AT1R was lower compared to Ang II. Perfusion pressure of isolated perfused rat kidneys increased less by Ang P than by Ang II. Blood pressure of SHR treated with PLP decreased significantly. Blood pressure of WKY rats treated with Ang II was increased to hypertensive values, whereas blood pressure of WKY rats cotreated with Ang II and PLP was not.ConclusionPLP induces a post‐translational modification of Ang II decreasing blood pressure in rats. Assuming that increased PLP intake in the form of vitamin B6 might reduce blood pressure in hypertensive patients, PLP might be a cost‐effective drug against hypertension.
- University of Córdoba Spain
- University of Southern Denmark Denmark
- RWTH Aachen University Germany
- Maastricht University Netherlands
- Andalusian Health Service Spain
Male, hypertension, Inbred SHR, Calcium/metabolism, Cost-Benefit Analysis, Myocytes, Smooth Muscle, 610, Blood Pressure, angiotensin II, Type 1/metabolism drug effects, In Vitro Techniques, vitamin B6, Rats, Inbred WKY, Blood Pressure/drug effects, Receptor, Angiotensin, Type 1, vitamin B, Angiotensin, renin–angiotensin–aldosterone system, Rats, Inbred SHR, Pyridoxal Phosphate/pharmacology analogs & derivatives therapeutic use, Humans, Animals, Inbred WKY, Pyruvates, Protein Processing, Cells, Cultured, Aorta, info:eu-repo/classification/ddc/610, Post-Translational/drug effects, Vascular/drug effects metabolism, Angiotensin II, Hypertension/drug therapy, Kidney/drug effects metabolism, pyridoxal-5′-phosphate, pyruvamide–angiotensin II, Rats, Perfusion, pyridoxal-5'-phosphate, Pyridoxal Phosphate, Vitamin B Complex, Hypertension, Angiotensin II/pharmacology, Muscle, Female, Smooth, Protein Processing, Post-Translational, Receptor
Male, hypertension, Inbred SHR, Calcium/metabolism, Cost-Benefit Analysis, Myocytes, Smooth Muscle, 610, Blood Pressure, angiotensin II, Type 1/metabolism drug effects, In Vitro Techniques, vitamin B6, Rats, Inbred WKY, Blood Pressure/drug effects, Receptor, Angiotensin, Type 1, vitamin B, Angiotensin, renin–angiotensin–aldosterone system, Rats, Inbred SHR, Pyridoxal Phosphate/pharmacology analogs & derivatives therapeutic use, Humans, Animals, Inbred WKY, Pyruvates, Protein Processing, Cells, Cultured, Aorta, info:eu-repo/classification/ddc/610, Post-Translational/drug effects, Vascular/drug effects metabolism, Angiotensin II, Hypertension/drug therapy, Kidney/drug effects metabolism, pyridoxal-5′-phosphate, pyruvamide–angiotensin II, Rats, Perfusion, pyridoxal-5'-phosphate, Pyridoxal Phosphate, Vitamin B Complex, Hypertension, Angiotensin II/pharmacology, Muscle, Female, Smooth, Protein Processing, Post-Translational, Receptor
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