ABSTRACT
La adrenomedulina (ADM), péptido vasodilatador de 52 aminoácidos, ubícuo, posee múltiples efectos fisiológicos que contribuyen a respuestas homeostáticas. Se encuentra en concentraciones importantes en la glándula suprarrenal, el pulmón, el sistema cardiovascular y el renal. Ejerce acciones biológicas a través de sus receptores AM1 y AM2, heterodímeros constituidos por el receptor semejante al receptor de calcitonina (CLR) y proteínas modificadoras de la actividad del receptor (RAMPs), CLR/RAMP2 y CLR/RAMP3, respectivamente. La principal vía de señalización es la adenilato ciclasa/AMPc en patologías cardiovasculares y renales, así como en la sepsis. Los niveles plasmáticos de ADM se elevan proporcionalmente con el incremento de la presión sanguínea y con el grado de daño renal, en pacientes con hipertensión arterial; así mismo, dichos niveles se correlacionan con el grado de hipertrofia cardíaca y arterial. La ADM tiene efectos renales, tubulares, ya que tiene acción diurética y natriurética; posee efectos vasodilatadores que producen aumento de la tasa de filtración glomerular y del flujo sanguíneo renal. Este péptido inhibe la proliferación y la generación de radicales libres en células mesangiales; actúa inhibiendo la secreción de aldosterona en la zona glomerulosa y de endotelina-1 en células musculares lisas vasculares. Se ha propuesto como marcador de riesgo en diversas patologías, especialmente en la insuficiencia renal crónica; en esta patología, que cursa con hipertrofia compensadora de los glomérulos y proliferación del mesangio, la administración de ADM disminuye los niveles de proteinuria, lo que sugiere que además de un importante rol modulador en la presión arterial, pudiera ser una opción terapéutica para la insuficiencia renal crónica.
Adrenomedullin (AM) is a potent vasodilatory 52-aminoacid peptide hormone, ubiquitous with multiple physiological effects which contribute to homeostatic responses. Significantly, it is distributed in the adrenal gland, lung, cardiovascular and renal system. The biological effects of AM are directly mediated by specific receptors as heterodimers composed of the calcitonin-receptor-like receptor (CLR) and one of two receptor activity modifying proteins (RAMP2 or RAMP3). The CLR/RAMP2 (AM1 receptor) is more highly AM-specific than The CLR/RAMP3 (AM2 receptor). Plasma levels of AM are elevated proportionately to the increase in blood pressure and degree of renal damage in patients with hypertension; likewise, these levels are correlated with the degree of heart and arterial hypertrophy. AM has renal vasodilatory, natriuretic and diuretic actions; increased glomerular filtration rate and renal blood flow. AM inhibits proliferation and reactive oxygen species generation in mesangial cells; also inhibits aldosterone secretion in the zona glomerulosa and endothelin-1 in vascular smooth muscle cells. Therefore, it is proposed as a new marker in various diseases, especially chronic renal failure. This disease presents compensatory hypertrophy of the glomeruli and mesangial proliferation, administration of AM reduces the levels of proteinuria, suggesting that AM has an important modulator role in blood pressure and could be a therapeutic option for chronic renal failure.
Subject(s)
Humans , Adrenomedullin/physiology , Kidney/physiology , Adrenomedullin/therapeutic use , Kidney/physiopathology , Kidney Failure, Chronic/drug therapyABSTRACT
BACKGROUND: Leakage from colonic anastomosis is a major complication causing increased mortality and morbidity. Ischemia is a well-known cause of this event. This study was designed to investigate the effects of adrenomedullin on the healing of ischemic colon anastomosis in a rat model. METHODS: Standardized left colon resection 3 cm above the peritoneal reflection and colonic anastomosis were performed in 40 Wistar rats that were divided into four groups. To mimic ischemia, the mesocolon was ligated 2 cm from either side of the anastomosis in all of the groups. The control groups (1 and 2) received no further treatment. The experimental groups (3 and 4) received adrenomedullin treatment. Adrenomedullin therapy was started in the perioperative period in group 3 and 4 rats (the therapeutic groups). Group 1 and group 3 rats were sacrificed on postoperative day 3. Group 2 and group 4 rats were sacrificed on postoperative day 7. After careful relaparotomy, bursting pressure, hydroxyproline, malondialdehyde, interleukin 6, nitric oxide, vascular endothelial growth factor, and tumor necrosis factor alpha levels were measured. Histopathological characteristics of the anastomosis were analyzed. RESULTS: The group 3 animals had a significantly higher bursting pressure than group 1 (p<0.05). Hydroxyproline levels in group 1 were significantly lower than in group 3 (p<0.05). The mean bursting pressure was significantly different between group 2 and group 4 (p<0.05). Hydroxyproline levels in groups 3 and 4 were significantly increased by adrenomedullin therapy relative to the control groups (p<0.05). When all groups were compared, malondialdehyde and nitric oxide were significantly lower in the control groups (p<0.05). When vascular endothelial growth factor levels were compared, no statistically significant difference between groups was observed. Interleukin 6 and tumor necrosis factor alpha were significantly decreased by adrenomedullin therapy (p<0.05). The healing parameters and inflammatory changes (e.g., granulocytic cell infiltration, necrosis, and exudate) were significantly different among all groups (p<0.05). CONCLUSION: Adrenomedullin had positive effects on histopathologic anastomotic healing in this experimental model of ischemic colon anastomosis.