Role of magnesium in hypertension

Magnesium affects blood pressure by modulating vascular tone and reactivity. It acts as a calcium channel antagonist, it stimulates production of vasodilator prostacyclins and nitric oxide and it alters vascular responses to vasoactive agonists. Magnesium deficiency has been implicated in the pathogenesis of hypertension with epidemiological and experimental studies demonstrating an inverse correlation between blood pressure and serum magnesium levels. Magnesium also influences glucose and insulin homeostasis, and hypomagnesemia is associated with metabolic syndrome. Although most epidemiological and experimental studies support a role for low magnesium in the pathophysiology of hypertension, data from clinical studies have been less convincing. Furthermore, the therapeutic value of magnesium in the management of hypertension is unclear. The present review addresses the role of magnesium in the regulation of vascular function and blood pressure and discusses the implications of magnesium deficiency in experimental and clinical hypertension, in metabolic syndrome and in pre-eclampsia.     

内源性一氧化碳在大鼠高血压发病中的作用

本实验研究内源性血红素氧化酶／一氧化碳系统在大鼠高血压发病听作用。２,４二甘油次卟啉锌是体内ＨＯ活必抑制剂 。     

Role of the adrenal cortex and sodium in the pathogenesis of human hypertension.

After 30 years of continuous research into the mechanisms of human hypertension, we summarize the results obtained by the members of the multidisciplinary research group on hypertension of the Clinical Research Institute of Montreal on the disturbances of minerlocorticoid activity in a rigorously selected group of patients with early, mild essential hypertension. We attempt to integrate these findings with those of many other groups working on other aspects of hypertensive cardiovascular diseases. On the assumption that the increased peripheral resistance responsible for hypertension results from an imbalance or a disturbance of the equilibrium between the sympathetic nervous system and norepinephrine on one hand, and the vascular tone, sensitivity and responsiveness of the arterial smooth muscle to norepinephrine and to angiotensin II on the other hand, three models that fit the experimental and clinical facts as known at present are described.     

Metabolic dysfunction in the pathogenesis of pulmonary hypertension

Pulmonary artery hypertension is characterized by proliferation in the resistance vessels. A recent study in Science Translational Medicine (Sutendra et al., 2010) found that increased fatty acid oxidation and a shift in the glycolysis/glucose oxidation ratio may be central to the pathogenesis of this process, suggesting that these abnormalities comprise novel treatment targets.     

Critical developmental periods in the pathogenesis of hypertension

Hypertension is one of the major risk factor of cardiovascular diseases, but after a century of clinical and basic research, the discrete etiology of this disease is still not fully understood. One reason is that blood pressure is a quantitative trait with multifactorial determination. Numerous genes, environmental factors as well as epigenetic factors should be considered. There is no doubt that although the full manifestation of hypertension and other cardiovascular diseases usually occurs predominantly in adulthood and/or senescence, the roots can be traced back to early ontogeny. The detailed knowledge of the ontogenetic changes occurring in the cardiovascular system of experimental animals during particular critical periods (developmental windows) could help to solve this problem in humans and might facilitate the age-specific prevention of human hypertension. We thus believe that this approach might contribute to the reduction of cardiovascular morbidity among susceptible individuals in the future.     

Role of endothelin and nitric oxide in the pathogenesis of arterial hypertension in autosomal dominant polycystic kidney disease

The pathogenesis of arterial hypertension in autosomal dominant polycystic kidney disease (ADPKD) is complex and likely dependent on interaction of hemodynamic, endocrine and neurogenic factors. We decided to evaluate the role of endothelin (ET1) and nitric oxide (NO) in the regulation of arterial blood pressure (BP) and to determine plasma levels of ET1 and NO in the group of patients with ADPKD. The ADPKD group (18 patients, 6 men + 12 women, mean age 44.6+/-11.7 years, with creatinine clearancecorrig > 1.1 ml/s) was compared with a control group of 27 healthy volunteers of comparable age. Plasma levels of ET1 assessed by direct RIA determination in the group of ADPKD patients (11.03+/-1.8 fmol/ml) were significantly increased (p<0.001) in comparison with the control group (2.66+/-0.58 fmol/ml), while no significant differences were observed between normotensive and hypertensive patients in the ADPKD group. Serum levels of NO were evaluated according to the determination of serum levels of their metabolites - nitrites/nitrates. Serum levels of NO in the group of ADPKD patients (39.85+/-.38 micro mol/l) were significantly higher (p<0.05) in comparison with the control group (22.7+/-1.20 micro mol/l), whereas in the ADPKD group no significant differences were observed between normotensive and hypertensive patients. Thus, our study supports the concept of complex alteration of both vasoconstrictor and vasodilator systems in the pathogenesis of arterial hypertension in ADPKD.     

Role of thrombin in the pathogenesis of atherosclerosis

Atherosclerosis is an arterial disease associated with inflammation. Thrombin is a procoagulant and proinflammatory serine protease that contributes to the pathology of atherosclerosis by enhancing the expression of cell adhesion molecules, inducing the secretion of proinflammatory cytokines, activating inflammatory responses in atherosclerotic plaques, stimulating proliferation of aortic smooth muscle cells, and exacerbating vascular lesions at sites of injury. Hence, thrombin appears to be an important target for treatment of atherosclerosis and thrombin pharmacological inhibitors have significant therapeutic potency for suppressing inflammatory responses in cardiovascular diseases. This review summarizes the proinflammatory signaling functions of thrombin as well as the therapeutic potency of thrombin inhibitors in the pathogenesis of atherosclerosis and hence their potential therapeutic value in this condition.     

Role of magnesium in genomic stability

In cellular systems, magnesium is the second most abundant element and is involved in basically all metabolic pathways. At physiologically relevant concentrations, magnesium itself is not genotoxic, but is highly required to maintain genomic stability. Besides its stabilizing effect on DNA and chromatin structure, magnesium is an essential cofactor in almost all enzymatic systems involved in DNA processing. Most obvious in studies on DNA replication, its function is not only charge-related, but very specific with respect to the high fidelity of DNA synthesis. Furthermore, as essential cofactor in nucleotide excision repair, base excision repair and mismatch repair magnesium is required for the removal of DNA damage generated by environmental mutagens, endogenous processes, and DNA replication. Intracellular magnesium concentrations are highly regulated and magnesium acts as an intracellular regulator of cell cycle control and apoptosis. As evident from animal experiments and epidemiological studies, magnesium deficiency may decrease membrane integrity and membrane function and increase the susceptibility to oxidative stress, cardiovascular heart diseases as well as accelerated aging. The relationship to tumor formation is more complex; magnesium appears to be protective at early stages but promotes the growth of existing tumors. With respect to the magnesium status in humans, the daily intake in most industrialized countries does not reach the current recommended daily dietary allowances (RDA) values, and thus marginal magnesium deficiencies are very common.     

Role of chemokines in the pathogenesis of asthma

The prevalence of asthma has risen drastically in the last two decades, with a worldwide impact on health care systems. Although several factors contribute to the development of asthma, inflammation seems to be a common factor that leads to the most severe asthmatic responses. In the past decade, researchers have characterized a large group of chemotactic cytokines, also known as chemokines, which are implicated in asthmatic inflammation. These chemokines control and direct the migration and activation of various leukocyte populations. Targeting chemokines should lead to new ways of controlling the inflammatory asthmatic response.     

The renal afferent nerves in the pathogenesis of hypertension

The renal nerves play a role in the pathogenesis of hypertension in a number of experimental models. In the deoxycorticosterone acetate - salt (DOCA-NaCl) hypertensive rat and the spontaneously hypertensive rat (SHR) of the Okamoto strain, total peripheral renal denervation delays the development and blunts the severity of hypertension and causes an increase in urinary sodium excretion, suggesting a renal efferent mechanism. Further, selective lesioning of the renal afferent nerves by dorsal rhizotomy reduces hypothalamic norepinephrine stores without altering the development of hypertension in the SHR, indicating that the renal afferent nerves do not play a major role in the development of hypertension in this genetic model. In contrast, the renal afferent nerves appear to be important in one-kidney, one-clip and two-kidney, one-clip Goldblatt hypertensive rats (1K, 1C and 2K, 1C, respectively) and in dogs with chronic coarctation hypertension. Total peripheral renal denervation attenuates the severity of hypertension in these models, mainly by interrupting renal afferent nerve activity, which by a direct feedback mechanism attenuates systemic sympathetic tone, thereby lowering blood pressure. Peripheral renal denervation has a peripheral sympatholytic effect and alters the level of activation of central noradrenergic pathways but does not alter sodium or water intake or excretion, plasma renin activity or creatinine clearance, suggesting that efferent renal nerve function does not play an important role in the maintenance of this form of hypertension. Selective lesioning of the renal afferent nerves attenuates the development of hypertension, thus giving direct evidence that the renal afferent nerves participate in the pathogenesis of renovascular hypertension.     

Aldosterone and magnesium in essential arterial hypertension

Thirty mildly hypertensive patients and 27 patients with severe essential hypertension and high levels of aldosterone were selected for a study of the relationship between plasma aldosterone and magnesium in essential arterial hypertension; levels of calcium and potassium were also studied. Thirty-six individuals were used as a control group. Our findings indicate that as plasma aldosterone levels increase, serum magnesium levels decrease correspondingly: in mild hypertensives with low levels of plasma aldosterone p less than 0.05 and in the most severely hypertensive patients with high levels of plasma aldosterone p less than 0.001. In this latter group we also found an inverse correlation between serum magnesium and systolic arterial pressure (p less than 0.001) and diastolic pressure (p less than 0.01). In these patients a significant increase in urinary excretion of magnesium was found, with levels 3 times higher than in the control group. These findings suggest a close relationship between changes in plasma aldosterone and magnesium. Possibly the aldosterone contributes through this mechanism to maintaining the hypertensive state in essential arterial hypertension. This action is exercised directly through the kidney, leading to a small but constant urinary loss of magnesium. This in turn leads to a chronic depletion of magnesium in hypertensives who have high levels of plasma renin activity and highly elevated plasma aldosterone.