Inhibición dual de la neprilisina y del receptor de la angiotensina (ARNI): una alternativa en los pacientes con falla cardiaca / Dual angiotensin receptor and neprilysin inhibition (ARNI): an alternative for patients with cardiac failure

La falla cardiaca (FC) es la causa más común de admisión hospitalaria en adultos en el mundo. Además, de su importante prevalencia la FC tiene un alta tasa de mortalidad, se estima que aproximadamente el 50% de los pacientes con FC mueren a los 5 años posterior al egreso hospitalario. Esto ha motivado el desarrollo de nuevas terapias seguras y efectivas para el manejo de esta entidad. El LCZ696 es un inhibidor dual de la neprilisina y del receptor de angiotensina II que demostró en estudios de fase III disminuir el desenlace primario de muerte cardiovascular y hospitalización por empeoramiento de la FC y muerte global. Probablemente el LCZ696 se convertirá en la piedra angular del manejo en pacientes con FC con fracción de eyección deprimida.

Cardiac failure (CF) is the most common cause of hospital admission in adults all over the world. In addition to its important prevalence, CF presents a high mortality rate. It is estimated that approximately 59% of patients with CF die within 5 years after the admission. This has been the motivation for the development of new, safe and effective therapies aimed at the management of this disease. LCZ696 is an angiotensin II receptor-neprilysin inhibitor; phase III studies have shown it decreases the primary outcome of cardiovascular death and admission due to worsening of the CF and global death. LCZ696 could probably become the cornerstone of the management of patients with CF with depressed ejection fraction.

Angiotensin II receptor and myocardial remodeling in hypertension / 中国药理学通报

Angiotensin II (Ang II ) is an effector of rein-angiotensin system. Ang II receptors mediate its biological effects. An analysis of radioactive ligand demostrated that mammalian exists AT1 receptor and AT2 receptor subtype. AT1 receptor exists three isoforms, AT1A, AT1B and AT1c receptor subtype in rat and mouse. The AT3 and the AT4 subtype receptors had been cloned, but their structure and function were unknown. The AT1 receptor belongs to the superfamily of seven trans-membrane domain, G-protein-coupled receptors and was 20%~ 30% homologous to other G-protein-coupled receptors. The AT1 receptor mainly exists in vessel, heart and adrenal glands in adult animals. The AT2 receptor only has 32% amino acid sequences homologous to AT1 receptor and mainly exists in embronic tissue and intersti-tium. Recent studies have shown that the AT1 receptor may mediate most of the biological functionof Ang I . The AT1 receptor mediates promoting the expression of growth-related inducible transcription factors such as c-fos, c-jun and c-myc, and inducing myocardial cell hypertrophy, cardiac fibroblasts proliferation and interstitial collagen deposition. The AT1 receptor antagonist can reverse myocardial hypertrophy and collagen accumulation induced by hypertension, but the AT2 receptor antagonist can't. The biological function of the AT2 receptor is little known. The AT2 receptor may mediate inhibit on of growth factor-induced cell proliferation, oposite AT1 receptor-induced mi-togenic effect and induce apoptosis. The AT1 receptor and AT2 receptor subtype in myocardial tissue may regulate the genesis and development of myocardial remodeling in hypertension togather.