Division of Medical Drugs, College Hospital Pedro Ernesto, State College of Rio de Janeiro, Avenida 28 de Setembro, 77 Sala 329, 20551-030, Rio de Janeiro, RJ, Brazil
Division of Medical Drugs, College Hospital Pedro Ernesto, State College of Rio de Janeiro, Avenida 28 de Setembro, 77 Sala 329, 20551-030, Rio de Janeiro, RJ, Brazil
Division of Medical Drugs, College Hospital Pedro Ernesto, State College of Rio de Janeiro, Avenida 28 de Setembro, 77 Sala 329, 20551-030, Rio de Janeiro, RJ, Brazil
Division of Medical Drugs, College Hospital Pedro Ernesto, State College of Rio de Janeiro, Avenida 28 de Setembro, 77 Sala 329, 20551-030, Rio de Janeiro, RJ, Brazil
Summary
1. Introduction
Major hypertension is the commonest type of blood strain elevation whose trigger stays unknown. Nonetheless, many elements have been implicated in its pathogenesis, such because the renin-angiotensin-aldosterone system and the sympathetic nervous system hyperactivation. As well as, adjustments in intracellular ions similar to calcium, sodium, potassium, and magnesium have additionally been associated to hypertension.
Within the final years, the prevalence of hypertension is round 25–30% in developed international locations [1], and several other remedies have been proposed for the BP management and prevention of its onset. Among the many varied research regarding non-pharmacological remedies, there may be want for life-style change with the inclusion of standard bodily exercise and wholesome consuming habits.
Observational research have proven {that a} food plan wealthy in potassium, magnesium, and calcium, current primarily in vegetables and fruit, is related to decrease incidence and mortality from heart problems [2]. Particularly, magnesium has been the goal of many research [3], contemplating that there’s a vital inverse correlation between serum magnesium ranges and incidence of cardiovascular ailments [4]. As well as, hypertensive sufferers usually exhibit decreased intracellular concentrations of magnesium, whereas the contents of sodium and calcium are sometimes elevated in comparison with normotensive topics [5, 6].
The dietary advice (Really helpful Dietary Allowances/RDA) for magnesium is 400 to 420 mg every day for grownup males and 310 to 320 mg every day for grownup ladies. Nonetheless, consumption is much under this advice, and the excessive prevalence of this deficiency has been related to a number of persistent ailments. Magnesium is present in most meals, however in various concentrations. Leafy greens, nuts, complete grains, fruits, and legumes are thought of as meals with high-magnesium concentrations [7].
With a purpose to collect extra details about the affiliation of magnesium with cardiovascular ailments, we carried out a story evaluation of the literature by way of the PubMed database with the next descriptor: magnesium, intracellular magnesium, hypertension, arterial stiffness, and endothelial perform. We included narrative opinions, experimental protocols, and managed research within the final 15 years (1996–2011), and case stories had been excluded.
2. Physiological Features and Pathophysiological Actions of Magnesium
The mineral magnesium is the second most plentiful intracellular cation and is concerned in a number of necessary biochemical reactions [8]. It’s recognized that magnesium has antiarrhythmic impact and may affect blood strain ranges by modulating vascular tone. Adjustments in extracellular magnesium content material are in a position to modify the manufacturing and launch of nitric oxide (NO), ensuing within the alteration of arterial easy muscle tone by affecting calcium concentrations. Magnesium additionally participates in glucose metabolism and insulin homeostasis. For these causes, it has been instructed that magnesium deficiency or adjustments in its metabolism are associated to the pathophysiology of hypertension, atherosclerosis, insulin resistance, and diabetes (Determine 1) [9].
Elevated ranges of extracellular magnesium inhibit calcium inflow. Conversely, decreased extracellular magnesium prompts calcium inflow by way of calcium channels. Low intracellular magnesium concentrations stimulate inositol-trisphosphate-(IP3-) mediated mobilization of intracellular calcium and scale back Ca2+-ATPase exercise. Thus, calcium efflux and sarcoplasmic reticular calcium reuptake are decreased, resulting in cytosolic accumulation of calcium and elevated intracellular calcium focus, which is a vital issue for vasoconstriction. Elevated intracellular ranges of magnesium lead to decreased intracellular free calcium focus selling vasodilation [10]. The motion of magnesium as a calcium channel blocker might also assist to cut back the discharge of calcium and thus lowering vascular resistance. As well as, magnesium additionally prompts the Na-Okay ATPase pump that controls the stability of those minerals contributing to the homeostasis of electrolytes in cells [11].
Smaller concentrations of magnesium appear to be related to decreased serum HDL-cholesterol together with elevated LDL-cholesterol and triglycerides ranges [9]. Moreover, deficiency of this mineral has been beforehand associated to oxidative stress, proinflammatory state, endothelial dysfunction, platelet aggregation, insulin resistance, and hyperglycemia [12].
Excessive ranges of magnesium might enhance manufacturing of adenosine triphosphate (ATP) and intracellular glucose utilization, since magnesium acts as a cofactor of all reactions involving ATP switch [13]. Insulin appears to be one of the necessary elements that regulate plasma and intracellular magnesium concentrations. It has been instructed that an ATPase-dependent pump is concerned within the mechanism by which insulin regulates the erythrocyte magnesium content material [14]. Then again, intracellular magnesium might play a task in modulating insulin-mediated glucose uptake and vascular tone. Decreased urinary magnesium losses have been implicated in higher metabolic management [15]. Low plasma and intracellular magnesium ranges might contribute to lowering insulin sensitivity. In reality, suppression of intracellular free magnesium concentrations is understood to lower mobile glucose utilization and thus to advertise peripheral insulin resistance as a postreceptor defect [16].
Regarding insulin homeostasis, there’s a speculation that there’s elevated secretion of insulin and adrenaline in hypomagnesemia with the intention to keep magnesium and mobile cAMP (3′,5′-cyclic adenosine monophosphate) focus [17]. Moreover, the intracellular focus of magnesium seems to be depending on the extracellular stage, and its inflow by way of calcium channel is voltage dependent. Extracellular magnesium can competitively inhibit calcium channels and decide decreased secretion of insulin. This inhibition doesn’t happen when there isn’t a magnesium within the extracellular house, leading to increased insulin secretion [18].
Some research counsel the attainable position of intracellular magnesium on the exercise as a regulator of the primary communication channels of the cell membrane, suggesting that there could also be an affiliation between adjustments in intracellular content material of ions induced by supplementation of magnesium and its antihypertensive results [19].
3. Magnesium and Blood Strain
Experimental fashions of hypertension have been related to decreased serum and tissue ranges of magnesium. In spontaneously hypertensive rats (SHRs), enhance of blood strain arises from the age of younger adults, round 12 to 16 weeks of life, being attributed to a genetic element much like human important hypertension [20]. In SHR, and in addition in DOCA-salt mannequin, decreased ranges of intracellular magnesium have been famous in easy muscle cells and cardiomyocytes.
Magnesium supplementation had little antihypertensive impact in grownup SHR with well-established hypertension. In reality, the impact of supplementation was solely optimistic in youthful animals, when began within the prehypertensive section, stopping or at the least attenuating the event of hypertension [21]. This discovering is very suggestive of a extra protecting impact of supplemental magnesium, which can forestall or gradual the rise in blood strain at an early stage of hypertension.
In different experimental research, dietary magnesium deficiency was related to elevated blood strain in earlier normotensive animals, and magnesium supplementation was in a position to reverse this situation. Nonetheless, scientific trials of magnesium supplementation in hypertensive sufferers present divergent outcomes. Some research exhibit low serum magnesium ranges in hypertensive sufferers when put next with normotensive topics, and blood strain ranges discount after magnesium supplementation [3], though different research haven’t confirmed this discovering. For that reason, whereas satisfactory consumption of magnesium by way of food plan is advisable, supplementation of this mineral isn’t indicated as a part of antihypertensive remedy [22, 23].
Experimental, scientific, and epidemiological research have noticed an in depth inverse relationship between dietary consumption or supplementation of magnesium and blood strain stage, indicating the potential position of magnesium deficiency within the pathogenesis of important hypertension [24], however the mechanism is unclear. The consequences of magnesium on the sleek muscle cells progress and irritation could also be necessary.
A relationship has additionally been reported between the rennin-angiotensin system, magnesium, and blood strain. Hypertensive sufferers with excessive renin exercise have considerably decrease serum magnesium ranges than normotensive topics, and plasma renin exercise is inversely related to serum magnesium [25]. Hypertensive sufferers with out blood strain management might have hypomagnesemia. Hatzistavri and colleagues have proven that magnesium supplementation was related to slight discount of 24 h blood strain ranges in sufferers with delicate hypertension [3], which may be evaluated by ambulatory blood strain monitoring [26]. Then again, a examine evaluating the connection between serum magnesium, vascular dysfunction, hypertension, and atherosclerosis has not proven sufficient outcomes to assist this affiliation, indicating that low serum magnesium can’t be thought of a danger issue for growth of those situations [27].
4. Magnesium and Vascular Construction – “magnesium glycinate blood pressure”
Hypertension can be related to unfavorable adjustments in elastic properties of huge arteries. Some research have proven the unbiased prognostic position of arterial stiffness in cardiovascular occasions in hypertensive sufferers, which may be assessed by measurements of the heartbeat wave velocity (PWV) [33–35]. Nonetheless, there are a number of research exhibiting the affect of magnesium on this situation up to now. Van Laecke and colleagues have reported that serum hypomagnesemia related to hypertension, endothelial dysfunction, dyslipidemia, and irritation might have an effect on vascular stiffness in sufferers who underwent kidney transplantation for the reason that low serum magnesium was independently related to PWV assessed by SphygmoCor [36]. In an experimental examine evaluating the construction of the carotid artery in rats, magnesium deficiency was related to hypertrophic vascular transforming, which was attenuated by supplementation of this ion. These findings counsel that magnesium deficiency alters the vascular mechanical properties in younger animals and could also be a mechanism concerned within the pathogenesis of hypertension, atherosclerosis, and different cardiovascular ailments [37].
Different attainable mechanisms of magnesium motion are anti-inflammation, antioxidion, and modulation of cell progress properties. In reality, the manufacturing of reactive oxygen species is often elevated within the vasculature of hypertensive sufferers, and the involvement of magnesium may happen by way of the discount of irritation and oxidative stress [38]. Magnesium has antioxidant properties that would attenuate detrimental results of oxidative stress on the vasculature, thereby stopping elevated vascular tone and contractility [39].
5. Magnesium and Vascular Perform
Endothelial dysfunction refers to an imbalance within the endothelial manufacturing of mediators that regulate vascular tone, platelet aggregation, coagulation, and fibrinolysis. There’s a worsening within the endothelium-dependent leisure, which may be attributable to each lack of NO bioavailability as adjustments within the manufacturing of different endothelium-derived vasoactive substances primarily endothelin-1 and angiotensin II.
The position of magnesium within the endothelial dysfunction has been mentioned elsewhere. Certainly, it has been reported that magnesium modifies the vascular tone by regulating endothelium and easy muscle cell capabilities together with an necessary position within the classical pathway of NO launch. Experiments in animals have additionally confirmed elevated manufacturing of prostacyclin and NO by magnesium, selling endothelium-independent and endothelium-dependent vasodilation [40].
The peripheral vascular resistance could also be modified by magnesium, additionally by way of the regulation of responses to vasoactive brokers, significantly angiotensin II, endothelin, and prostacyclin. Animals poor in magnesium have introduced excessive ranges of endothelin-1, whose values have been decreased after supplementation of this mineral [41].
A examine that adopted greater than 90,000 postmenopausal ladies confirmed that dietary magnesium consumption was inversely related to plasma concentrations of inflammatory markers similar to interleukin-6, C-reactive protein (CRP), and tumor necrosis factor-α [7]. This identical examine emphasised that magnesium consumption may enhance endothelial dysfunction and irritation and may play a task in stopping metabolic syndrome.
There are a number of research demonstrating the connection between magnesium supplementation, endothelial perform, arterial stiffness, and carotid intima-media thickness. Some stories level out useful results of magnesium supplementation in enhancing endothelial perform within the brachial artery in sufferers with coronary artery illness [42], coronary heart failure [43], and diabetes mellitus [44], whereas others present favorable final result of magnesium supplementation by way of enchancment of insulin sensitivity [45, 46].
6. Magnesium Supplementation
Magnesium may be supplemented in numerous methods, similar to oxide, hydroxide, chelate, sulfate, and citrate. Magnesium sulfate, for instance, can be utilized as anticonvulsant remedy in preeclampsia because of its neuroprotective motion and a attainable position in regulating vascular tone [47].
Some research have proven blood strain decreasing after magnesium supplementation. The administration of magnesium oxide (400 mg every day) for eight weeks in sufferers with hypertension can scale back blood strain ranges, and this discount has already been detected in workplace measurements and by ambulatory blood strain monitoring [29]. A examine of 48 topics has demonstrated that 600 mg of magnesium pidolate per day was in a position to scale back blood strain ranges within the supplemented sufferers when in comparison with the group with no supplementation [3]. This identical dosage of complement was additionally related to discount of serum whole ldl cholesterol, LDL-cholesterol, and triglycerides and enchancment of insulin resistance.
Haenni and colleagues reported optimistic results of magnesium supplementation with the intention to affirm the connection between the metabolism of this mineral and alteration of endothelial perform by exhibiting elevated endothelium-dependent vasodilatation after magnesium infusion [48]. Moreover, one other examine confirmed that persistent magnesium supplementation was in a position to enhance endothelial perform in sufferers with coronary artery illness [42]. Some optimistic and unfavorable outcomes after magnesium supplementation are proven in Desk 1. A meta-analysis evidenced a weak causal correlation between magnesium supplementation and blood strain discount, and double-blind placebo managed trials are wanted to find out the impact of magnesium supplementation on cardiovascular outcomes [49].