Aplicaciones y proyecciones de los antagonistas del receptor de mineralocorticoides en el tratamiento de patologías cardiovasculares / Mineralocorticoid receptor antagonists and therapeutic strategies of cardiovascular damage

In recent years, much attention has focused on the role of aldosterone and mineralocorticoid receptors (MRs) in the pathophysiology of hypertension and cardiovascular disease. Patients with primary aldosteronism, in whom angiotensin II levels are low, have a higher incidence of cardiovascular complications than patients with essential hypertension. The Randomized Aldactone Evaluation Study (RALES) demonstrated that adding a non-specific MR antagonist, spironolactone, to a standard therapy that included angiotensin-converting enzyme (ACE) inhibitors, loop diuretics, and digoxin, significantly reduced morbidity and mortality in patients with moderate to severe heart failure. Similarly, the Eplerenone Post-Acute Myocardial Infarction Heart Failure Efficacy and Survival Study (EPHESUS) showed that the addition of a selective MR antagonist (ARM), eplerenone, to an optimal medical therapy reduces morbidity and mortality among patients with acute myocardial infarction complicated by left ventricular dysfunction and heart failure. These data suggest that aldosterone induces cardiac injury through activation of MRs and support the notion that MR blockade has beneficial effects on aldosterone-dependent cardiac injury, through mechanisms that cannot be simply explained by hemodynamic changes. Although, MRA are highly effective in patients with heart failure, the risk of hyperkalemia should not be overlooked. Serious hyperkalemia events were reported in some MRA clinical trials; however these risks can be mitigated through appropriate patient selection, dose selection, patient education, monitoring, and follow-up.

Daño arterial asociado a la enfermedad renal crónica: evaluación mediante técnicas de laboratorio no invasivo en pacientes hemodializados / Assesment of arterial damage by noninvasive peripheral arterial tonometry in non-diabetic hemodialysis patients

Background: Hemodialysis patients (HD) display high rates of cardiac disease and mortality. The cardiovascular morbidity and mortality of HD patients is attributable in a significant proportion to endothelial dysfunction, arterial stiffness, and vascular calcifications. Aim: To measure vascular reactivity in HD subjects and compare them with healthy volunteers. Material and Methods: Forty eight non diabetic patients aged 58 ± 4.6 years (29 males) on hemodialysis for a mean lapse of 4.8 years were studied. Arterial stiffness was measured in the radial artery. Pulse wave velocity was measured by noninvasive peripheral arterial tonometry in carotid and femoral arteries. Endothelial function was assessed, measuring reactive hyperemia response after a 5 min period of ischemia. As a control, all values were also measured in age and gender-matched healthy volunteers. Results: Arterial stiffness was significantly higher in HD patients than controls (23.9 ± 3.3 and 18.4 ± 3.4% respectively, p < 0.05). HD subjects had an increased pulse wave velocity (10.0 ± 0.8 and 7.6 ± 0.9 m/s respectively, p < 0.05). A reduction in the change in pulse amplitude pressure, as a measure of arterial dysfunction, was only observed in male patients (1.7± 0.4 and2.7 ± 0.4 respectively p < 0.01). Conclusions: Noninvasive assessment of peripheral vascular function may be useful for the identification of patients at risk for late cardiac events.

Evolución del compromiso cardiovascular de pacientes insuficientes renales, en hemodiálisis, sin bloqueo del eje renina-angiotensina / Cardiovascular assessment of non diabetic patients on hemodialysis

Background: Diabetes mellitus is an important risk factor for cardiovascular complications among patients on hemodialysis. However, the incidence of these complications among non diabetic patients on hemodialysis is not well known. Aim: To assess the incidence of cardiovascular complications in non diabetic patients on hemodialysis. Patients and methods: Seventy five non diabetic patients aged 55.6 ± 17 years (48 males), receiving hemodialysis three times a week were evaluated with laboratory tests, echocardiogram anda carotid ultrasound. In 26 patients, interleukin 6, tumor necrosis factor alpha, and intercellular adhesión molecule (ICAM-1) were also measured. Patients were followed during two years. Results: The mean lapse of dialysis therapy was 6.5 ±5 years. The main cause of renal failure was hypertension. Sixty two percent had systolic hypertension, 86 percent had concentric left ventricular hypertrophy, 43 percent had atrial dilatation and 60 percent had calcifications in the thoracic aorta. Compared with normal controls, patients had higher levels of interleukin 6, tumor necrosis factor alpha and ICAM-1. Carotid media thickness was also higher and increased in the two years of follow up. No correlations were found between ventricular hypertrophy and dialysis lapse, packed red cell volume, calcium phosphorus product, parathormone levels or median arterial pressure. No cardiovascular events were recorded during the follow up period. Conclusions: Non diabetic patients on chronic hemodialysis have a high frequency of ventricular hypertrophy, carotid media thickening, aortic calcifications and an increase in proinflammatory cytokines.

Effect of corticosteroids on electrolyte transport in the descending colon of the rat

El efecto de corticosteroides sobre el movimiento de electrolitos fue estudiado en un modelo de saco evertido del colón distal de rata. La corticosterona tiene un significativo efecto estimulador, dependiente de la dosis, sobre la transferencia de sodio y líquido. Con la baja dosis de 10-9M la corticosterona aumentó la absorción de sodio en 29.4 micronEq g-1 h-1, valor que fue estadisticamente mayor que el efecto de dexametasona 10-9M. Con la alta concentración de 10-7M el efecto de corticosterona sobre el movimiento de sodio fue dos veces el de aldosterona o dexametasona en concentraciones equimolares. En cambio, el efecto de corticosterona sobre el movimiento de potasio fue bifásico: a baja concentración (10-9M) se encontró una significativa secreción neta, mientras que con corticosterona 10-7M se observó absorción de potasio. La dexametasona aumentó significativamente la secreción neta de potasio, mientras que el efecto de aldosterona sobre el movimiento de potasio no fue significativamente diferente de los controles. Estos datos sugieron que el glucocorticoide nativo, corticosterona, ejerce un control regulatorio de la función de los electrolitos y líquidos del colon