Trakia Journal of Sciences, No 3, pp 277-282, 2019 Copyright © 2019 Trakia University Available online at: http://www.uni-sz.bg ISSN 1313-7050 (print) ISSN 1313-3551 (online) doi:10.15547/tjs.2019.03.017 Review EFFECTS OF VITAMIN D ON THE RENIN-ANGIOTENSIN SYSTEM L. Pashova-Stoyanova*, A. Tolekova Department of Physiology, Pathophysiology and Pharmacology, Medical Faculty, Trakia University, Stara Zagora, Bulgaria ABSTRACT The renin-angiotensin-aldosterone system (RAAS) is a complex endocrine system of enzymes, proteins and peptides that occupies a key position in the regulation of a number of important physiological processes, such as arterial pressure, water and electrolyte homeostasis. Its activity, flow and regulation are affected by a large number of mediators, substances and diseases one of which is vitamin D. Vitamin D is involved in the regulation of many physiological processes with great importance. Vitamin D deficiency is associated with an increased risk of impaired renal function, cardiovascular disease, diabetes mellitus, metabolic disorders, affecting RAAS and other pathways. Key words: vitamin D, renin-angiotensin system INTRODUCTION blood pressure and intravascular volume, the The renin-angiotensin system is a unique system is the subject of detailed and thorough regulatory system by its nature and research. Following the discovery of renin by characteristics. It has numerous effects on the Robert Tigerstedt in 1897, a new era in the regulation of a number of systems and development of physiology, biochemistry of mediators, and at the same time is influenced peptide hormones, the pathophysiology of the by the impact of a number of substances and hypertonic disease, endocrinology, factors. pharmacology and a number of scientific research inquiries and angiotensins were Vitamin D is beneficial for the regulation of launched (1-7). bone metabolism, calcium homeostasis and affects different aspects of people`s health. The renin-angiotensin-aldosterone system There is evidence that vitamin D is important (RAAS) is a complex endocrine system of for normal blood pressure, sugar levels, insulin enzymes, proteins and peptides that occupies a resistance, immune system, reproductive key position in the regulation of a number of system and many more. important physiological processes, such as arterial pressure, water and electrolyte Vitamin D affects the main effector of the homeostasis (8-11). renin-angiotensin system on different levels and leads to changes in the regulation of The activity of RAAS is determined by the different mediators. velocity of renin secretion by the juxtaglomerular apparatus of the kidney (12, Renin-angiotensin system 13). The renin-angiotensin system has a key role in salt balance and cardiovascular homeostasis. Touyz (2002) points out that Its activity, flow Validated as a major humoral regulator of and regulation are affected by a large number ___________________________ of diseases in connection with the onset of *Correspondence to: Lilia Pashova-Stoyanova, humoral, metabolic and other changes. Bulgaria, Stara Zagora, Trakia University, Medical Knowledge of the pathophysiological features, Faculty, Armeiska 11 str, Department of pathogenesis and mechanisms for the Physiology, Pathophysiology and Pharmacology development of these disabilities helps to corresponding author:, e-mail: [email protected], Tel: understand the disease thoroughly and to create 0897 427 123 Trakia Journal of Sciences, Vol. 17, № 3, 2019 277 PASHOVA-STOYANOVA L., et al. specific, targeted and effective ways to providing calcium and phosphate ion counteract (14). deposition. According to Yilmaz (2012) it also participates actively in the processes of bone Rahimi et al (2014) suggest that there is a close and dentin, and this property is the opposite of relationship between the major RAAS effector, parathyroid hormone action (parathyroid namely angiotensin II, insulin resistance, the hormone regulates the processes and activity of progression of diabetic nephropathy, osteoclasts, which in turn are responsible for retinopathy, neuropathy, and cardiovascular the degradation of bone tissue) (22, 23). lesions in patients with type 2 diabetes. There is also a close association between RAAS and Studies by Sipahi (2017) show that vitamin D the development of metabolic disorders, is involved in the absorption of calcium and metabolic syndrome and its components and phosphorus in the small intestine, and under its complications. action a specific protein is formed on the surface of the small intestinal mucosa, known Studies by Agarwal (2003) and Arendshorts as calcium binding protein, responsible for (1999) report that inclusion of drugs from the calcium binding and transport via active angiotensin-converting enzyme (ACE) transport through the walls of the small inhibitors and angiotensin receptor blockers intestine (24). (sartans) in the treatment of patients with metabolic syndrome, pre-diabetic conditions There is evidence from studies by Sipahi and type 2 diabetes significantly reduces the (2017) and Atalay (2017) that in the kidneys risk of new diabetes, reduces proteinuria and vitamin D affects the phosphate ion reduces the progression of nephropathy to reabsorption, increasing it and increasing its terminal renal disease, which supports the blood concentration (hyperphosphatemia) in thesis of a link between RAAS and metabolic the course of phosphorous exchange, and this parameters (15-17). effect is also opposed to the parathormone effect (24, 25). Vitamin D: role, effect, physiological importance Mostafa et al (2016) report that regardless of Vitamin D belongs to the family of the fat- the source of supply to the body with vitamin soluble vitamins and can be found under D (food, sun exposure, additives), it is different names, including anti-rheumatic necessary to double pass the process of vitamin, calciferol and others. Vitamin D hydroxylation to obtain the active form of discovery and isolation initiate in-depth studies vitamin D, namely 1,25- of its role in the body, biological functions and dihydroxycholecalciferol. reactions in the cases of deficiency (18, 19). The author states that the first hydroxylation According to Heaney (2008) and Holick process takes place in the liver, forming 25- (2007) vitamin D is available in several hydroxycholecalciferol (25-OH-D3) or 25- different forms, from D1 to D5, each hydroxyvitamin D3. The second hydroxylation exhibiting different biological activity and process takes place in the kidney to form the functions. Only two of the forms are found in final active metabolite, namely 1.25 nature, namely vitamin D2, also known as dihydroxycholecalciferol (1,25- (OH) 2-D3). ergocalciferol and vitamin D3, also called Their distinctive and characteristic feature is cholecalciferol. Ergocalciferol is essentially faster and stronger effect than even vitamin D derived from ergosterin contained in wheat, itself. In renal structures, the parathyroid irradiated with ultraviolet rays and is inactive hormone plays the role of a stimulator of vitamin D. Ergocalciferol is taken by food, and particular importance in the conversion of 25 after subcutaneous deposition under the (OH) D to 1,25- (OH) 2-D3. influence of ultraviolet rays, it is transformed into active vitamin D2 which rapidly is The reactions of conversion of the starting absorbed into the blood and can be stored for vitamin D into its active metabolite are several months in the adipose tissue. The real accomplished with the enzymes 25- anti-rheumatic vitamin is cholecalciferol or hydroxylase in the liver and 1-alpha- vitamin D3 (20, 21). hydroxylase in the kidney, both of which belong to the family of cytochrome P450- Autier (2007) points out that vitamin D exerts dependent steroidal hydroxylase. a significant influence on the cells responsible for bone tissue synthesis (osteoblasts), 278 Trakia Journal of Sciences, Vol. 17, № 3, 2019 PASHOVA-STOYANOVA L., et al. According to Zittermann (2003) there is a • It improves insulin secretion from pancreatic close interdependence and interrelation Beta cells and improves insulin sensitivity (18, between parathyroid hormone and vitamin D. 20). The synthesis of its active form requires the presence of parathormone and the action of Numerous studies and experimental studies parathyroid hormone on bone tissue requires have shown the unambiguous and extremely the active principle of vitamin D3 (26, 27). important role of vitamin D in protecting against the development of metabolic Holick (2004) explains that 1,25- (OH) 2-D3 disorders. Since metabolic damage has been performs its calcium function by binding to the associated with numerous factors and vitamin D receptor (VDR), which in turn binds metabolic disorders have developed at to DNA sequences (VDREs) and regulates a different levels, it has been shown that the fat- large number of genes. Activation of VDR in soluble vitamin significantly improves lipid intestines, bones, kidneys and parathyroid profile and blood sugar disorders, which are glands maintains a normal concentration of some of the initial and leading to the calcium and phosphorus and hence bone manifestation of the entire spectrum of a mineralization (28). component of the metabolic syndrome. Evidence from Basit (2013) indicates that all Sibuh (2018) points out that in experiments cells of acquired immunity (monocytes, with rats subjected to high fructose diet, a dendritic cells, B cells, T cells, NK cells) significant improvement in serum glucose and express VDR continuously or