Responses in extracellular and intracellular calcium and magnesium in aldosteronism.
ABSTRACT We hypothesized the hypercalciuria and hypermagnesuria that accompany aldosteronism could be pharmacologically attenuated to prevent shifts in extracellular and intracellular levels of these divalent cations and the adverse outcomes associated with them. Accordingly, rats administered aldosterone/salt treatment (ALDOST) were cotreated with either hydrochlorothiazide (Hctz), to selectively reabsorb urinary Ca2+, or with Hctz plus spironolactone (Hctz+Spi), where Spi retards the excretion of these cations in both urine and feces. We monitored urinary excretion and responses in extracellular and intracellular Ca2+ and Mg2+, together with indices of oxi/nitrosative stress in plasma and ventricular tissue. At 4 weeks ALDOST we found the following: (1) hypercalciuria was reduced by Hctz and normalized by Hctz+Spi, and this combination, unlike Hctz alone, also rescued hypermagnesuria; (2) the decrease in plasma-ionized [Ca2+]o was not seen with Hctz or Hctz+Spi, whereas Spi cotreatment protected against a decline in [Mg2+]o; (3) the Ca2+ loading of peripheral blood mononuclear cells and cardiac tissue was not seen with Hctz+Spi; and (4) the induction of oxi/nitrosative stress, expressed as reduced plasma alpha1-antiproteinase activity and activation of gp91(phox) subunit of NADPH oxidase in inflammatory cells invading intramural coronary arteries of the right and left ventricles, together with vascular fibrosis, was completely prevented by Spi cotreatment. In rats with aldosteronism, cotreatment with Hctz+Spi more effectively (vis-à-vis Hctz alone) protects against adverse iterations in extracellular and intracellular concentrations of Ca2+ and Mg2+, as well as the appearance of oxi/nitrosative stress to prevent the proinflammatory vascular phenotype.
- SourceAvailable from: tswj.com[Show abstract] [Hide abstract]
ABSTRACT: Aldosterone not only contributes to salt and water homeostasis, but also exerts direct cardiovascular and renal effects. Numerous experimental and clinical studies indicate that aldosterone participate in cardiac alterations associated with hypertension, heart failure, diabetes and other pathological entities. It is important to mention that dietary salt is a key factor in aldosterone-mediated cardiovascular damage, since damage was more evident in animals on a high-salt diet than animals on a low salt diet. A pathophysiological action of aldosterone involves development of extracellular matrix and fibrosis, inflammation, stimulation of reactive oxygen species production, endothelial dysfunction, cell growth and proliferation. Many studies showed local extra-adrenal production of aldosterone in brain blood vessel, and the heart, which contribute in an important manner to the pathological actions of this mineralocorticoid. Several studies such as RALES, EPHESUS, 4E and others, recently showed that mineralocorticoid-receptor (MR) antagonists, alone or in combination with ACE inhibitors or ARBs, reduced the risk of progressive target organ damage and hospitalization in patients with hypertension and heart failure. These clinical benefits support the therapeutic usefulness of MR antagonists.The Scientific World Journal 02/2006; 6:413-24. DOI:10.1100/tsw.2006.68 · 1.73 Impact Factor
Article: Role of magnesium in hypertension[Show abstract] [Hide abstract]
ABSTRACT: 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.Archives of Biochemistry and Biophysics 03/2007; 458(1):33-9. DOI:10.1016/j.abb.2006.05.005 · 3.04 Impact Factor
- [Show abstract] [Hide abstract]
ABSTRACT: Hyperaldosteronism is associated with hypertension, cardiovascular fibrosis, and electrolyte disturbances, including hypomagnesemia. Mechanisms underlying aldosterone-mediated Mg(2+) changes are unclear, but the novel Mg(2+) transporters TRPM6 and TRPM7 may be important. We examined whether aldosterone influences renal TRPM6/7 and the TRPM7 downstream target annexin-1 and tested the hypothesis that Mg(2+) administration ameliorates aldosterone-induced cardiovascular and renal injury and prevents aldosterone-associated hypertension. C57B6 mice were studied (12 weeks, n=8 to 9/group); (1) control group (0.2% dietary Mg(2+)), (2) Mg(2+) group (0.75% dietary Mg(2+)), (3) aldosterone group (Aldo, 400 microg/kg/min and 0.9% NaCl drinking water), and (4) Aldo+Mg(2+) group. Blood pressure was unaltered by aldosterone and was similar in all groups throughout the experiment. Serum Na(+) was increased and serum K(+) and Mg(2+) decreased in the Aldo group. Aldo mice had hypomagnesuria and proteinuria, and renal, cardiac, and aortic fibrosis, which were normalized by Mg(2+) supplementation. Renal and cardiovascular expression of interleukin-6, VCAM1 and COX2 was increased in the Aldo group. Magnesium attenuated renal and cardiac interleukin-6 content and decreased renal VCAM1 and cardiac COX2 expression (P<0.05). Aldosterone decreased expression of renal TRPM7 and the downstream target annexin-1 (P<0.05) without effect on TRPM6. Whereas Mg(2+) increased mRNA expression of TRPM6 and TRPM7, it had no effect on TRPM7 and annexin-1 protein content. Our data demonstrate that aldosterone mediates blood pressure-independent renal and cardiovascular fibrosis and inflammation through Mg(2+)-sensitive pathways. We suggest that altered Mg(2+) metabolism in hyperaldosteronism may relate to TRPM7 downregulation and that Mg(2+) protects against cardiovascular and renal damaging actions of aldosterone.Hypertension 04/2008; 51(4):915-21. DOI:10.1161/HYPERTENSIONAHA.107.100339 · 7.63 Impact Factor