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Vitamin D Receptor Deficiency Does Not Affect Blood Pressure and Heart Function.
Front Physiol 2019; 10:1118FP

Abstract

Vitamin D is thought to play a role in blood pressure regulation, which in turn can influence cardiovascular risk. Several meta-analyses of cohort studies found low serum levels of 25-hydroxyvitamin D to be associated with increased blood pressure or increased cardiovascular morbidity and mortality in the general population. Active vitamin D mediates its function via the vitamin D receptor (Vdr), which is a ligand-activated transcription factor. A suitable model to examine the causal role of vitamin D in blood pressure regulation and heart function is the Vdr knockout (Vdr-/-) mouse. To elucidate the role of vitamin D on blood pressure, heart function, and cardiac myocyte size, we conducted a long-term study using Vdr-/- mice and well-defined diets. Group 1 comprised Vdr-/- mice that received a high-calcium, high-phosphorus rescue diet to prevent hypocalcemia and a rickets phenotype. Groups 2 and 3 included Vdr+/+ mice that were fed either the rescue diet or a control diet containing normal amounts of these minerals. As Vdr is a nuclear factor that regulates transcription, we analyzed the renal mRNA expression and serum concentration of renin and found that the Vdr-/- group had an almost 50% higher renin mRNA expression in the kidney compared to both groups of Vdr+/+ mice. Additionally, serum concentration of renin in Vdr-/- mice was significantly higher than that of Vdr+/+ mice that received the rescue or control diet (+ 17%,+ 32%; P < 0.05). In contrast, renin activity was lower in Vdr-/- mice than in both groups of Vdr+/+ mice (P < 0.05). However, blood pressure, heart rate, cardiac myocyte sizes, and the expression of renal renin receptor, hepatic angiotensinogen and angiotensin II receptor, type 1, in kidney, liver and heart, did not differ between the three groups of mice. Additionally, data from transthoracic echocardiography did not indicate the role of Vdr on heart function, as the left ventricular ejection fraction, fractional shortening, and velocity of blood flow were comparable between the three groups. To conclude, the roles of Vdr and therefore most probably of vitamin D, in blood pressure regulation and heart function, were not confirmed by our findings.

Authors+Show Affiliations

Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Leipzig, Germany.Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Leipzig, Germany. Julius Bernstein Institute of Physiology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.Julius Bernstein Institute of Physiology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Leipzig, Germany.Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Leipzig, Germany. Julius Bernstein Institute of Physiology, Faculty of Medicine, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany.Institute of Agricultural and Nutritional Sciences, Martin Luther University Halle-Wittenberg, Halle (Saale), Germany. Competence Cluster for Nutrition and Cardiovascular Health (nutriCARD), Halle-Jena-Leipzig, Leipzig, Germany.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

31555149

Citation

Grundmann, Sarah M., et al. "Vitamin D Receptor Deficiency Does Not Affect Blood Pressure and Heart Function." Frontiers in Physiology, vol. 10, 2019, p. 1118.
Grundmann SM, Schutkowski A, Schreier B, et al. Vitamin D Receptor Deficiency Does Not Affect Blood Pressure and Heart Function. Front Physiol. 2019;10:1118.
Grundmann, S. M., Schutkowski, A., Schreier, B., Rabe, S., König, B., Gekle, M., & Stangl, G. I. (2019). Vitamin D Receptor Deficiency Does Not Affect Blood Pressure and Heart Function. Frontiers in Physiology, 10, p. 1118. doi:10.3389/fphys.2019.01118.
Grundmann SM, et al. Vitamin D Receptor Deficiency Does Not Affect Blood Pressure and Heart Function. Front Physiol. 2019;10:1118. PubMed PMID: 31555149.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Vitamin D Receptor Deficiency Does Not Affect Blood Pressure and Heart Function. AU - Grundmann,Sarah M, AU - Schutkowski,Alexandra, AU - Schreier,Barbara, AU - Rabe,Sindy, AU - König,Bettina, AU - Gekle,Michael, AU - Stangl,Gabriele I, Y1 - 2019/08/29/ PY - 2019/03/27/received PY - 2019/08/13/accepted PY - 2019/9/27/entrez PY - 2019/9/27/pubmed PY - 2019/9/27/medline KW - blood pressure KW - heart function KW - mice KW - vitamin D KW - vitamin D receptor SP - 1118 EP - 1118 JF - Frontiers in physiology JO - Front Physiol VL - 10 N2 - Vitamin D is thought to play a role in blood pressure regulation, which in turn can influence cardiovascular risk. Several meta-analyses of cohort studies found low serum levels of 25-hydroxyvitamin D to be associated with increased blood pressure or increased cardiovascular morbidity and mortality in the general population. Active vitamin D mediates its function via the vitamin D receptor (Vdr), which is a ligand-activated transcription factor. A suitable model to examine the causal role of vitamin D in blood pressure regulation and heart function is the Vdr knockout (Vdr-/-) mouse. To elucidate the role of vitamin D on blood pressure, heart function, and cardiac myocyte size, we conducted a long-term study using Vdr-/- mice and well-defined diets. Group 1 comprised Vdr-/- mice that received a high-calcium, high-phosphorus rescue diet to prevent hypocalcemia and a rickets phenotype. Groups 2 and 3 included Vdr+/+ mice that were fed either the rescue diet or a control diet containing normal amounts of these minerals. As Vdr is a nuclear factor that regulates transcription, we analyzed the renal mRNA expression and serum concentration of renin and found that the Vdr-/- group had an almost 50% higher renin mRNA expression in the kidney compared to both groups of Vdr+/+ mice. Additionally, serum concentration of renin in Vdr-/- mice was significantly higher than that of Vdr+/+ mice that received the rescue or control diet (+ 17%,+ 32%; P < 0.05). In contrast, renin activity was lower in Vdr-/- mice than in both groups of Vdr+/+ mice (P < 0.05). However, blood pressure, heart rate, cardiac myocyte sizes, and the expression of renal renin receptor, hepatic angiotensinogen and angiotensin II receptor, type 1, in kidney, liver and heart, did not differ between the three groups of mice. Additionally, data from transthoracic echocardiography did not indicate the role of Vdr on heart function, as the left ventricular ejection fraction, fractional shortening, and velocity of blood flow were comparable between the three groups. To conclude, the roles of Vdr and therefore most probably of vitamin D, in blood pressure regulation and heart function, were not confirmed by our findings. SN - 1664-042X UR - https://www.unboundmedicine.com/medline/citation/31555149/Vitamin_D_Receptor_Deficiency_Does_Not_Affect_Blood_Pressure_and_Heart_Function L2 - https://doi.org/10.3389/fphys.2019.01118 DB - PRIME DP - Unbound Medicine ER -