Sistema renina-angiotensina, deterioro cognitivo y demencia. Implicancias terapéuticas de su inhibición / Renin-angiotensin system, cognitive deterioration and dementia. therapeutic implications of their Inhibition

La acumulación de amiloide, la edad y la enfermedad vascular son los principales factores de riesgo para desarrollar una demencia. Existe un interjuego entre los factores genéticos y vasculares para desarrollar la enfermedad de Alzheimer de inicio tardío. La activación sostenida del sistema renina Angiotensina parece ocupar un papel destacado en la fisiopatología de las demencias incluyendo la enfermedad de Alzheimer. El tratamiento antihipertensivo con inhibidores de la enzima de conversión de Angiotensina tanto como el bloqueo de los receptores de la Angiotensina II, parecen superiores sobre otros fármacos en la prevención de las demencias

The age, aggregation of amyloid, and vascular disease are major risk factors for developing dementia. There is interplay between genetic and vascular factors to develop late-onset Alzheimer's disease. Sustained the renin angiotensin system activation seems to occupy an important role in the pathophysiology of dementia including Alzheimer's disease. Antihypertensive treatment with angiotensin-converting enzyme inhibitors and angiotensin II receptor blockade, seem superior over other drugs in the prevention of dementia

Effect of angiotensin-(1-7) on reperfusion arrhythmias in isolated rat hearts

There is increasing evidence that angiotensin-(1-7) (Ang-(1-7) is an endogenous biologically active component of the renin-angiotensin system (RAS). In the present study, we investigated the effects of Ang-(1-7) on reperfusion arrhythmias in isolated rat hearts. Isolated rat hearts were perfused with two different media, i.e., Krebs-Ringer (2.52 mM CaCl2) and low-Ca2+ Krebs-Ringer (1.12 mM Cacl2) and low-Ca2+ Krebs-Ringer (1.12 mM CaCl2). In hearts perfused with Krebs-Ringer, Ang-(1-7) produced a concentration-dependent (27-210 nM) reduction in coronary flow (25 percent reduction at highest concentration), while only slight and variable changes in contaction force and heart rate were observed. Under the same conditions, angiotensin II (Ang II; 27 and 70 nM) produced a significant reduction in coronary flow (39 percent and 48 percent, respectively) associated with a significant increase in force. A decrease in heart rate was also observed. In low-Ca2+ Krebs-Ringer solution, perfusion with Ang-(1-7) or Ang II at 27 nM concentration produced similar changes in coronary flow, contraction force and heart rate. In isolated hearts perfused with normal Krebs- Ringer, Ang-(1-7) produced a significant enhancement of reperfusion arrhythmias revealed by an increase in the incidence and duration of ventricular tachycardia and ventricular fibrillation (more than 30-min duration). The faciliation of reperfusion arrhythmias by Ang-(1-7) was associated with an increase in the magnitude of the decreased force usually observed during the postischemic period. The effects of Ang-(1-7) were abolished in isolated rat hearts perfused with low-Ca2+ Krebs-Ringer. The effect of Ang II (27 nM) was similar but less pronounced than that of Ang-(1-7) at the same concentration. These results indicate that the heart is a site of action for Ang-(1-7) and suggest that this heptapeptide may be involved in the mediation of the cardiac effects of the RAS.