scholarly journals Effects of aliskiren on hemodynamic parametersin daunorubicin -induced acute cardiomyopathy in rats

2019 ◽  
Vol 9 (1) ◽  
pp. 103-107
Author(s):  
Md. Salahuddin Ansari ◽  
Rohit Saraswat ◽  
Pankaj Sharma ◽  
Md. Sarfaraz Alam

Daunorubicin ((DNR)) used in oncological practice against a wide variety of solid organ tumors and hematologic malignancies, including leukemia, lymphoma, breast cancer, lung cancer, multiple myeloma and sarcoma. however clinical use of this agent is limited due to cardiomyopathy and cardiac heart failure. one of the important player in the development of cardic hypertrophy and reperfusion injury is renin-angiotensin system. Aliskiren (ALK) a recent drug of a direct inhibitor of the renin enzyme. It Protect cardiomyopathy by the inhibition of the renin activity. Present study is towards the evaluation of protective effcets of ALK 50 and 100 mg/kg/day in rats. The systolic, diastolic, mean BP and heart rate were significantly (P< 0.01) increased in DNR control group as compared to normal control group. Thus the results provide clear evidence that the ALK pretreatment offered significant protection against DNR-induced Hemodynamic parameters changes.  Keywords: Daunorubicin, Cardiomyopathy, Aliskiren, Telmisartan and Hemodynamic parameters

2001 ◽  
Vol 281 (6) ◽  
pp. R1854-R1861 ◽  
Author(s):  
Raynald Bergeron ◽  
Michael Kjær ◽  
Lene Simonsen ◽  
Jens Bülow ◽  
Dorthe Skovgaard ◽  
...  

The study examined the implication of the renin-angiotensin system (RAS) in regulation of splanchnic blood flow and glucose production in exercising humans. Subjects cycled for 40 min at 50% maximal O2 consumption (V˙o 2 max) followed by 30 min at 70% V˙o 2 maxeither with [angiotensin-converting enzyme (ACE) blockade] or without (control) administration of the ACE inhibitor enalapril (10 mg iv). Splanchnic blood flow was estimated by indocyanine green, and splanchnic substrate exchange was determined by the arteriohepatic venous difference. Exercise led to an ∼20-fold increase ( P < 0.001) in ANG II levels in the control group (5.4 ± 1.0 to 102.0 ± 25.1 pg/ml), whereas this response was blunted during ACE blockade (8.1 ± 1.2 to 13.2 ± 2.4 pg/ml) and in response to an orthostatic challenge performed postexercise. Apart from lactate and cortisol, which were higher in the ACE-blockade group vs. the control group, hormones, metabolites, V˙o 2, and RER followed the same pattern of changes in ACE-blockade and control groups during exercise. Splanchnic blood flow (at rest: 1.67 ± 0.12, ACE blockade; 1.59 ± 0.18 l/min, control) decreased during moderate exercise (0.78 ± 0.07, ACE blockade; 0.74 ± 0.14 l/min, control), whereas splanchnic glucose production (at rest: 0.50 ± 0.06, ACE blockade; 0.68 ± 0.10 mmol/min, control) increased during moderate exercise (1.97 ± 0.29, ACE blockade; 1.91 ± 0.41 mmol/min, control). Refuting a major role of the RAS for these responses, no differences in the pattern of change of splanchnic blood flow and splanchnic glucose production were observed during ACE blockade compared with controls. This study demonstrates that the normal increase in ANG II levels observed during prolonged exercise in humans does not play a major role in the regulation of splanchnic blood flow and glucose production.


Author(s):  
Isabella Viana Gomes Schettini ◽  
Débora Vargas Faria ◽  
Leilismara Sousa Nogueira ◽  
Alba Otoni ◽  
Ana Cristina Simões e Silva ◽  
...  

Abstract Introduction: Studies have shown that the renin angiotensin aldosterone system (RAAS) and inflammation are related to kidney injury progression. The aim of this study was to evaluate RAAS molecules and chemokine (C-C motif) ligand 2 (CCL2) in 82 patients with chronic kidney disease (CKD). Methods: Patients were divided into two groups: patients diagnosed with CKD and patients without a CKD diagnosis. Glomerular filtration rate (GFR) and albumin/creatinine ratio (ACR) were determined, as well as plasma levels of angiotensin-(1-7) [Ang-(1-7)], angiotensin-converting enzyme (ACE)1, ACE2, and plasma and urinary levels of CCL2. Results: CCL2 plasma levels were significantly higher in patients with CKD compared to the control group. Patients with lower GFR had higher plasma levels of ACE2 and CCL2 and lower ratio ACE1/ACE2. Patients with higher ACR values had higher ACE1 plasma levels. Conclusion: Patients with CKD showed greater activity of both RAAS axes, the classic and alternative, and higher plasma levels of CCL2. Therefore, plasma levels of RAAS molecules and CCL2 seem to be promising prognostic markers and even therapeutic targets for CKD.


2021 ◽  
Vol In Press (In Press) ◽  
Author(s):  
Seyedeh Mahsa Poormoosavi ◽  
Behnam Ghorbanzadeh ◽  
Mohammad Amin Behmanesh ◽  
Kooshan Ghobadi ◽  
Reza Amirgholami

Background: Tacrolimus is an immunosuppressive drug broadly used to avoid rejection of tissue transplantation. Some studies suggest that tacrolimus has destructive effects on the male reproductive system due to activation of the renin-angiotensin system (RAS) and inflammation. Objectives: The present study aimed at determining the toxic effects of tacrolimus on testis and evaluating the blocking effects of captopril and losartan on angiotensin-converting enzyme (ACE) and angiotensin receptors, respectively, in rats. Methods: The present experimental study was conducted on 36 adult male Wistar rats (weighing 200 ± 20 g) randomly divided into six groups and treated based on the experimental design for 30 days. At the end of the intervention, the rats were anesthetized and their blood samples were obtained to measure the serum levels of testosterone and ACE2 enzyme. Also, both testes were removed for histopathological examinations after scarifying. Results: Tacrolimus decreased testosterone and ACE2 levels significantly. The ACE2 levels were lower in the groups treated with a combination of tacrolimus and losartan or captopril compared to the control group while testosterone level significantly increased in the groups receiving a combination of tacrolimus and captopril. The epithelial thickness of seminiferous tubules and the number of primary spermatocytes significantly decreased in the rats only receiving tacrolimus compared to the groups that received captopril and losartan, along with tacrolimus. Conclusions: According to the findings, the administration of captopril or losartan, along with tacrolimus, can decrease its testicular toxicity. Captopril and losartan act through blocking RAS but cannot improve ACE2 level; therefore, the recovery of testicle tissue might not be attributed to the ACE2 approach but to the anti-inflammatory effect.


1981 ◽  
Vol 240 (6) ◽  
pp. F545-F550
Author(s):  
P. C. Wong ◽  
B. G. Zimmerman ◽  
P. Friedman

The mechanism of enhanced renal prostaglandin (PG) release in the in situ pump-perfused kidney was studied in anesthetized dogs. Pump perfusion caused a gradual decrease in mean arterial blood pressure (BP) from 163 to 128 mmHg over an 80-min period. The renal arteriovenous level of PGE and plasma renin activity (PRA) were increased by a mean of 1.36 ng/ml and 22 ng AI.ml-1.h-1, respectively. In a second group of dogs treated with captopril, pump perfusion did not alter PGE or BP, but increased PRA. When the animals were treated with indomethacin, the renal arteriovenous levels of PGE and 6-keto-PGF1 alpha were not changed but PRA increased during the 80 min of pump perfusion. In a fourth group of dogs that had undergone renal denervation and phentolamine treatment, changes in PGE and BP occurred during pump perfusion similar to the changes in the control group, and 6-keto-PGF1 alpha release by the kidney also increased. The results indicate that renal PG release during group perfusion is mainly due to the activation of the renin-angiotensin system and that the hypotension due to pump perfusion is PG mediated.


Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Kenjiro Muta ◽  
Donald A Morgan ◽  
Justin L Grobe ◽  
Curt D Sigmund ◽  
Kamal Rahmouni

Mechanistic target of rapamycin complex 1 (mTORC1) is a molecular hub for signaling pathways mediating a wide range of cellular events involved in the regulation of various physiological and pathophysiological processes. We previously demonstrated that Angiotensin II (Ang II) activates mTORC1 and its downstream effector ribosomal protein S6 kinase in neurons in vitro . Here, we investigated the role of brain mTORC1 in hypertension and polydipsia induced by Ang II. In wild-type mice, acute stimulation of angiotensin type 1 receptor signaling by intracerebroventricular (ICV) injection of Ang II (1 μg, 30 min) activated mTORC1 signaling in the subfornical organ (SFO), a critical brain region in cardiovascular control and fluid balance, as indicated by the significant increase in the number of phosphorylated S6-positive cells (32±2 vs 13±3 in vehicle group). Similar upregulation of the mTORC1 pathway in the SFO was also found in the mice treated subcutaneously with Ang II (1000 ng/kg/min) using an osmotic minipump for 1 week (27±3 vs 11±2 in vehicle group). To verify functional roles of the Ang II activation of mTORC1 in the SFO, we utilized hypertensive and polydipsic transgenic mice (sRA) that have a hyperactive brain renin-angiotensin system, resulting in SFO-overproduction of Ang II. Interestingly, sRA mice exhibited substantially elevated phospho-S6 immunoreactivity only in the SFO (64±6 vs 36±8 in controls) but not in other cardiovascular regulatory regions including the paraventricular nucleus. ICV delivery of mTORC1 blocker, rapamycin (10 ng/day for 7 days) significantly (p<0.05) reduced daily water intake (-4.5±0.7 mL) compared to vehicle-treated sRA mice (-0.7±0.6 mL). In contrast, systolic blood pressure remained unchanged with rapamycin treatment (123±1 vs 125±4 mmHg in pre-treatment) and was consistently higher than the control group (110±4 mmHg). These results suggest that mTORC1 activity in the SFO is a critical determinant of the polydipsia evoked by Ang II.


Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 4502-4502
Author(s):  
Anita J. Kumar ◽  
Joseph R Carver ◽  
Noelle V. Frey

Abstract Abstract 4502 Background: The renin angiotensin system modulates hematopoiesis via local effects in the bone marrow. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may adversely impact hematopoiesis and time to engraftment in patients undergoing stem cell transplant (SCT). Our study assesses whether the use of ACEi or ARBs delays time to engraftment in patients with multiple myeloma undergoing a melphalan based autologous SCT. Methods: A retrospective review of 58 patients who underwent autologous SCT with a melphalan 200 mg/m2 conditioning regimen for multiple myeloma between January 1 and December 31, 2010 was performed. Neutrophil engraftment was defined as an absolute neutrophil count greater than or equal to 500 cells/uL that persisted for at least three days. Platelet engraftment was defined as achieving platelets of at least 20,000 cells/uL that persisted for at least three days. Time to engraftment was defined as number of days from Day 0 of SCT to the first day of platelet or neutrophil engraftment. Results: Of 58 evaluable patients, 47 underwent autologous SCT without an ACEi or ARB (control group), and 11 patients were given an ACEi or ARB (treatment group). Mean time to neutrophil engraftment was 11.5 days in the control group, and 11.3 days in treatment group (p=0.6). Mean time to platelet engraftment in control group was 13.5 days and 15.1 days in treatment group (p=0.2). There was no statistically significant difference between groups in time to neutropenic fever and length of hospital stay. Conclusion: Our study demonstrates no significant difference in time to engraftment, incidence of neutropenic fever, or length of hospital stay between patients receiving ACEi or ARBS compared to control subjects. We demonstrate that use of low to moderate dose ACEi or ARB is not associated with prolonged time to engraftment and is safe to use in patients undergoing autologous SCT for multiple myeloma. Disclosures: No relevant conflicts of interest to declare.


2008 ◽  
Vol 295 (5) ◽  
pp. F1512-F1518 ◽  
Author(s):  
Naro Ohashi ◽  
Tatsuo Yamamoto ◽  
Yanjie Huang ◽  
Taro Misaki ◽  
Hirotaka Fukasawa ◽  
...  

The differential roles of circulating and intrarenal renin-angiotensin system (RAS) in glomerulonephritis have not been elucidated. In this study, we investigated the levels of circulating and intrarenal RAS activity and urinary angiotensinogen (AGT) excretion in anti-thymocyte serum (ATS) nephritis induced by an ATS injection (ATS group). The effect of olmesartan, an angiotensin II (ANG II) type 1 receptor blocker (ARB), on the development of nephritis was also examined (ATS+ARB group). In addition, the rats received a saline injection instead of ATS (control group). Mesangial proliferation with transient proteinuria, which peaked at day 7, was significantly increased in the ATS group compared with the control group. The levels of glomerular AGT mRNA, intrarenal ANG II, and urinary AGT excretion in the ATS group were increased significantly at day 7 compared with the control group. Administration of olmesartan (ATS+ARB group) significantly decreased the levels of renal lesions, proteinuria, and intrarenal RAS activity compared with the ATS group. In addition, the levels of urinary AGT excretion correlated with the levels of glomerular damage, urinary protein excretion, and immunoreactivity for AGT and ANG II in kidney. On the other hand, plasma renin activity was significantly lower in the ATS group compared with the control group and significantly higher in the ATS+ARB group than in the ATS group. These data suggest that an increase in kidney-specific RAS activity, which parallels urinary AGT excretion, plays an important role in the development of ATS nephritis.


Cells ◽  
2021 ◽  
Vol 10 (7) ◽  
pp. 1767
Author(s):  
Driss Laghlam ◽  
Mathieu Jozwiak ◽  
Lee S. Nguyen

The renin–angiotensin system (RAS) has long been described in the field of cardiovascular physiology as the main player in blood pressure homeostasis. However, other effects have since been described, and include proliferation, fibrosis, and inflammation. To illustrate the immunomodulatory properties of the RAS, we chose three distinct fields in which RAS may play a critical role and be the subject of specific treatments. In oncology, RAS hyperactivation has been associated with tumor migration, survival, cell proliferation, and angiogenesis; preliminary data showed promise of the benefit of RAS blockers in patients treated for certain types of cancer. In intensive care medicine, vasoplegic shock has been associated with severe macro- and microcirculatory imbalance. A relative insufficiency in angiotensin II (AngII) was associated to lethal outcomes and synthetic AngII has been suggested as a specific treatment in these cases. Finally, in solid organ transplantation, both AngI and AngII have been associated with increased rejection events, with a regional specificity in the RAS activity. These elements emphasize the complexity of the direct and indirect interactions of RAS with immunomodulatory pathways and warrant further research in the field.


2008 ◽  
Vol 28 (5_suppl) ◽  
pp. 38-42 ◽  
Author(s):  
Devrim Bozkurt ◽  
Pinar Cetin ◽  
Savas Sipahi ◽  
Ender Hur ◽  
Hasim Nar ◽  
...  

Background Encapsulating peritoneal sclerosis (EPS) is a clinical syndrome associated with symptoms of ileus and irreversible sclerosis of both visceral and parietal peritoneum. Peritoneal dialysis (PD) patients rarely develop EPS, a severe life-threatening condition of unknown pathogenesis. Angiotensin II is known to promote fibrosis and inflammation in various tissues. Renin–angiotensin system (RAS) blockade provides advantages in the course of diseases such as hypertension, chronic kidney disease, and proteinuria. We have also previously shown that RAS blockade has beneficial effects on hypertonic (3.86%) PD solution-induced peritoneal alterations. Because it shares the same characteristics as other fibrotic processes, peritoneal fibrosis can benefit from RAS blockade. Objective To determine the advantages of RAS blockade in regression of EPS. Methods We divided 56 nonuremic albino Wistar rats into 6 groups: control group ( n = 10), daily intraperitoneal (IP) injection of 2 mL isotonic saline for 3 weeks; CG group ( n = 10), daily IP injection of 2 mL/200 g chlorhexidine gluconate (CG) for 3 weeks; resting group ( n = 10), daily IP injection of CG (0 – 3 weeks) plus peritoneal rest (4 – 6 weeks). After 3 weeks of being injected with CG (0 – 3 weeks), a fourth group ( n = 9) was treated with 100 mg/L enalapril (ENA group); a fifth group ( n = 10) was treated with 80 mg/L valsartan (VAL group), and a sixth group ( n = 7) was treated with 100 mg/L enalapril + 80 mg/L valsartan (ENA+VAL group) in drinking water for an additional 3 weeks (4 – 6 weeks). At the end, a 1-hour peritoneal equilibration test was performed with 25 mL 3.86% PD solution. Dialysate-to-plasma ratio of urea (D/P urea), dialysate WBC count, ultrafiltration volume (UF), and morphological changes of parietal peritoneum were examined. Results Exposure to CG for 3 weeks resulted in alterations in peritoneal transport (increased D/P urea, decreased UF volume; p < 0.05) and morphology (increased inflammation, neovascularization, fibrosis, and peritoneal thickness; p < 0.05). Peritoneal rest had some beneficial effect only on UF failure and dialysate cell count ( p < 0.05). However, RAS blockade was more effective than peritoneal rest with respect to UF volume, vascularity ( p < 0.05), and peritoneal thickness ( p > 0.05). Dual blockade of RAS had no additional beneficial effects. Conclusion We suggest that RAS blockade either with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers may be a more effective option than resting in the management of EPS.


1997 ◽  
Vol 136 (6) ◽  
pp. 656-660 ◽  
Author(s):  
Cipriano Garcia del Rio ◽  
María Rosario R Moreno ◽  
Antonio Osuna ◽  
Juan de Dios Luna ◽  
Joaquín García-Estañ ◽  
...  

Abstract Objective: We evaluated the influence of chronic blockade of the renin-angiotensin system on hypertension induced by long-term thyroxine (T4) administration. To this end, we determined the effects of chronic treatment with captopril on blood pressure, cardiac hypertrophy and other renal and metabolic variables of hypertensive hyperthyroid rats. Methods: T4 was administered s.c. at 0·38 μmol/kg per day and captopril was given in the drinking water (1·38 mmol/l). Both treatments were maintained for 6 weeks. Control rats received tap water. After the treatment period, the rats were placed in metabolic cages. Later, blood pressure was measured in conscious rats by intra-arterial determination. Results: T4-treated rats showed an increased mean arterial pressure (MAP) whereas, in rats treated with T4 plus captopril, MAP was similar to that of the control group. Captopril did not affect the increased heart rate or ventricular weight/body weight ratio of hyperthyroid rats, but it improved the reduced creatinine clearance of these animals. Conclusions: The elevation in blood pressure produced by long-term T4 administration was prevented by chronic blockade of the renin-angiotensin system. Captopril improved the renal function of hyperthyroid rats, but did not affect the relative cardiac hypertrophy of these animals. European Journal of Endocrinology 136 656–660


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