Effect of Cholecalciferol and Diuretics as Components of Combination Antihypertensive Therapy on Plasma Renin Activity and Endothelial Function in Patients With Arterial Hypertension

Aim. To evaluate the effect of cholecalciferol and diuretics as components of combination antihypertensive therapy (CAHT) on plasma renin activity (PRA) and endothelial function in patients with arterial hypertension (AH). Materials and methods. We included in this prospective study 153 patients with II-degree AH. Duration of follow-up was 15.8±1.8 months. Patients were divided into four groups: patients of group 0 received CAHT without cholecalciferol or diuretic; of group 1 - CAHT with cholecalciferol (2000 IU daily); of group 2 - CAHT with diuretic; of group 3 - CAHT with diuretic and cholecalciferol 2000 IU daily. Results. After treatment, the highest level of 25-hydroxy vitamin D (25(OH)D) (48.9 [34.3; 67.9] ng/ml) and its greatest dynamics (Δ) - (27.5 [6.2; 48.8] ng/mL) were observed in group 1. With diuretics blood level of 25(OH)D and its Δ were lower (p<0.05), than without diuretics. Reduction of plasma renin activity (PRA) compared to baseline occurred only in Group 1. It became lower (p=0.0005) than in group 2, in which we observed elevation of PRA. (Д PRA. 0.24 [0.42; 1.54] ng/ml/h). There were no significant changes of PRA in group 3. Lowering of systolic and diastolic BP (SBP and DBP) occurred in all groups. Greatest BP reduction was observed in group 3 (Д SBP -30.0 [-40.0, -10.0] mm Hg, Д DBP -10.0 [-20.0; 0.0] mm Hg). Combined intake of cholecalciferol and diuretic was associated with positive Д of serum nitrate/nitrite levels (p=1.38; p=0.02). Conclusions. Cholecalciferol and diuretics used as components of CAHT promoted greatest lowering of both SBP and DBP, elevated serum levels of nitrates/nitrites, and influenced PRA and serum level of 25(OH)D.

артериальная гипертензия, холекальциферол, диуретики, активность ренина плазмы, функция эндотелия, arterial hypertension, cholecalciferol, diuretics, plasma renin activity, endothelial function

1. Piepoli M. F., Hoes A. W., Agewall S. et al. 2016 European Guidelines on cardiovascular disease prevention in clinical practice. Eur Heart J. 2016;37 (29):2315-2381.

2. Forman J. Р. Plasma 25-hydroxy-vitamin D. levels and risk of incident hypertension. Hypertension 2007;49:1063-1069.

3. Vaidya A. Vitamin D. and hypertension: current evidence and future direction. Hypertension 2010;56 (5):774-779.

4. Плудовски П., Карчмаревич Э., Байер М. и др. Практические рекомендации по поступлению витамина D. и лечению его дефицита в центральной Европе -рекомендуемое потребление витамина D. среди населения в целом и в группах риска по дефициту витамина D. Журнал Гродненского государственного медицинского университета 2014;2:109-118

5. Li Y. C. Vitamin D: a negative endocrine regulator of the reninangiotensin system and blood pressure. J. Ster Biochem Molec Biol 2004;89-90:387-392.

6. Sechi L. A. Relationship of plasma renin with a prothrombotic state in hypertension: relevance for organ damage. Am J. Hypertens 2008;21 (12):1347-1353.

7. Tomaschitz A. Independent association between 1,25-dihydroxy-vitamin D., 25-hydroxyvitamin D. and the renin - angiotensin system The Ludwigshafen Risk and Cardiovascular Health (LURIC) study. Clinica Chimica Acta 2010;411:1354-1360.

8. Sugden J., Davies J., Witham M. et al. Vitamin D. improves endothelial function in patients with Type 2 diabetes mellitus and low vitamin D. levels. Diabet Med 2008;25:320-325.

9. Wong M. S., Delansome R., Man R. Y. et al. Vitamin D. derivatives acutely reduce endothelium-dependent contractions in the aorta of hypertensive. Am J. Physiol Heart Circ 2008;289: H289-96.

10. Li Y. C. Vitamin D. regulation of the rennin-angiotensin system. J. Cell Biochem 2003;88:327-331.

11. Kong J., Qiao G., Zhang Z. et al. Targeted vitamin D. receptor expression in juxtaglomerular cells suppresses rennin expression independent of parathyroid hormone and calcium. Kidney Int 2008;74 (12):1577-1581.

12. Molinari C., Uberti F., Grossini E. et al. 1a-25-dihydroxychole-calciferol induces nitric oxide production in cultured endothelial cells. Cell Physiol Biochem 2011;27 (6):661-8.

13. Vaidya A., Forman J. P., Hopkins P. N. et al. 25-hydroxyvitamin D. is associated with plasma rennin activity and the pressor response to dietary sodium intake in Caucasians. J. Renin-Angiotensin-Aldosterone System 2011;12 (3):311-319.

14. Imaoka M., Morimoto S., Kitano S. et al. Calcium metabolism in elderly hypertensive patients: possible participation of exaggerated sodium, calcium and phosphate excretion. Clin Exp Pharmacol Physiol 1991;18:631-641.

15. Ernst M., Moser M. Use of Diuretics in Patients with Hypertension. Hypertension 2009;361:2153-2164.

16. Dzau V. The cardiovascular continuum and renin-angiotensin-aldo-sterone system blockade. J. Hypertens Suppl 2005;23 (1):9-17.

17. Национальные рекомендации. Артериальная гипертензия: диагностика, лечение, профилактика. Мрочек А. Г., Сидоренко Г. И., Подпалов В. П. и др. Минск: 2010; 52

18. Mancia G. ESH/ESC Guidelines for the management of arterial hypertension 2013. J. Hypertension 2013;7 (31):1281-1357.

19. Воробьев А. П., Гелис Л. Г., Гуль Л. М. и др. Цифровой компьютерный интерпретирующий импедансный кардиограф: рук. оператора. РНПЦ Кардиология. Инженер-мед рук-во Интекард: Минск, 2012; 47

20. Moshage H., Kok B., Huizenga J. R. et al. Nitrite and nitrate determinations in plasma: a critical evaluation. Clin Chem 1995;41:892-896.

21. Янковская Л. В., Снежицкий В. А., Поворознюк В. В., Ляликов С. А. Влияние на уровень 25-гидроксивитамина D. и артериальное давление дополнительного приема холекальциферола при антигипертензивной терапии. Кардиология в Беларуси 2015;5 (42):140-150

22. Янковская Л. В., Кежун Л. В., Слободская Н. С. Влияние приема холекальциферола на активность ренина плазмы и функцию эндотелия у лиц с артериальной гипертензией. Рецепт 2016;5:542-553