Experimental studies clearly support the anti-inflammatory and anti-fibrotic effects of ACE2/ Ang-(1-7)/Mas axis. Clinical studies, especially phase III and IV trials, will be necessary to establish the therapeutic role of ACE2/Ang-(1-7)/Mas axis in controlling inflammation in different human diseases.
Pre-clinical evidence supports a relevant role for ACE2/Ang-(1-7)/Mas receptor axis in several neuropsychiatric conditions, including stress-related and mood disorders, cerebrovascular ischemic and hemorrhagic lesions and neurodegenerative diseases. However, very few data are available regarding the ACE2/Ang-(1-7)/Mas receptor axis in human CNS.
Novel compounds that activate and/or stimulate ACE2-Angiontensin-(1-7)-Mas receptor axis may also play a role in the treatment of CKD, mainly by controlling inflammatory response and pathways of fibrosis at kidney tissue. Clinical trials with these new pharmacological compounds will, in due course, determine whether this promise will become a helpful treatment.
Increased urinary levels of angiotensin-converting enzyme 2 and of Ang-(1-7) in fetuses with posterior urethral valve could represent a regulatory response to the intense inflammatory process triggered by posterior urethral valve.
Background:
Angiotensin Converting Enzyme (ACE) 2 is an important modulator of the
Renin Angiotensin System (RAS) and the RAS plays a central role in renovascular hypertension.
Very few studies investigated the role of components of the counterregulatory RAS axis (ACE2,
Ang-(1-7) and Mas receptor) in renovascular hypertension and the results are controversial.
Objective:
The aim of this study was to investigate the effects of Diminazene Aceturate (DIZE)
administration on renal function and renal inflammation parameters in 2K1C hypertensive rats.
Methods:
Male Wistar rats were divided into three experimental groups: sham-operated animals,
2K1C+saline and 2K1C+DIZE orally (1 mg/kg/day). At the end of the 30 days of treatment, renal
function was analyzed and kidneys from all the groups were collected and processed separately for
measurement of N-acetyl-beta-D-glucosaminidase (NAG) and Myeloperoxidase (MPO) activities,
cytokines, chemokines and nitric oxide levels.
Results:
Oral DIZE administration for 4 weeks in hypertensive rats attenuated renal dysfunction
and reduced the levels of MPO and NAG, cytokines and chemokines (IL1β, IL-6, TNF-α and
MCP-1) and increased urinary nitrate/nitrite levels in 2K1C hypertensive rats.
Conclusion:
Our findings showed that ACE2 activation may effectively improve renal alterations
and inflammation induced by renovascular hypertension.
. Conception and design of the study, interpretation of data, statistical analysis, histopathological examinations, manuscript preparation and writing, critical revision, final approval.
ABSTRACT PURPOSE:To characterize an experimental model of progressive renal disease induced by different degrees of nephrectomy in rats.
METHODS:Eighty male Wistar rats were divided into four experimental groups (n=20/group): sham surgery (control group), progressive degrees of nephrectomy leading to mild uremia (group 1), moderate uremia (group 2) and severe uremia (group 3). Ten animals of each group were followed for two or four weeks. At the end, blood and 24-hour urine samples were collected to determine renal function parameters. Urine output and water and food intake were daily monitored.
RESULTS:In rats of group 1, serum levels of creatinine and urea and microalbuminuria were increased, while reduced creatinine clearance (p<0.05, compared with control group), without changing blood pressure. Animals of group 2 had more accentuated alterations: increases in urinary output, blood pressure, serum concentrations of urea, creatinine, sodium, potassium, and in microalbuminuria, and reduction of creatinine clearance (p<0.05). Group 3 exhibited even more increased serum concentrations of urea, creatinine, sodium and potassium, blood pressure and microalbuminuria, and decreased creatinine clearance (p<0.05) in comparison with control group and unilateral nephrectomy.
CONCLUSION:Progressive nephrectomy in rats seems to be useful to study the physiopathology of chronic kidney disease and its mechanisms of progression.
Hypertensive rats subjected to chronic intracerebroventricular (ICV) infusion of Angiotensin‐(1‐7) presented attenuation of arterial hypertension, improvement the sensitivity of the baroreflex, restoration the cardiac autonomic tone and alteration the expression of cardiac RAS components. In this study we evaluated whether the acute increase in the brain levels of Ang‐(1‐7) modulates the gene expression of angiotensinergic receptors in the left ventricle of normotensive and hypertensive rats. Sprague‐Dawley (SD) and hypertensive rats that overexpress renin (TGR) were used. The animals were divided into four experimental groups: SD, ICV infusion of saline (3 mL/hour), n=5; SD, ICV infusion of Ang‐(1‐7) (2,5 mg/hour), n=5; TGR, ICV infusion of saline (3 mL/hour), n=4 and TGR, ICV infusion of Ang‐(1‐7) (2,5 mg/hour), n=4. Immediately after the ICV infusion, the animals were euthanized by decapitation and the left ventricle was removed and frozen on dry ice. The mRNA expression of AT1, AT2 and Mas receptor were evaluated by semi quantitative real time‐PCR using the delta delta CT method. The acute infusion of saline or Ang‐(1‐7) for 3 hours did not alter the gene expression of AT1 and Mas receptors in the left ventricle of the normotensive or hypertensive rats. In contrast, the acute infusion of Ang‐(1‐7) was capable of increasing the gene expression of AT2 receptors in SD (2.78±0.55 a.u. vs.1.17±0.35 a.u. in ICV saline group) and TGR(mRen2)27 (3.37±0.92 a.u. vs. 1.05±0.15 a.u. in ICV saline group). Short‐term ICV infusion of Ang‐(1‐7) in the brain alters gene expression of the AT2 receptor in the left ventricle of normotensive and hypertensive rats.
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