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effect of angiotensin 2 on the kidneys

Maryam Maleki, Jalal Hasanshahi, Fatemeh Moslemi
Background: Nitric oxide (NO) as a vasodilator factor has renoprotective effect against renal ischemia. The balance between angiotensin II (Ang II) and NO can affect kidney homeostasis. The aim of this study was to determine NO alteration in response to renin-Ang system vasodilator receptors antagonists (PD123319; Ang II type 2 receptor antagonist and A779; Mas receptor antagonist) in renal ischemia/reperfusion injury (IRI) in rats. Materials and Methods: Sixty-three Wistar male and female rats were used...
2018: Advanced Biomedical Research
P Kala, L Sedláková, P Škaroupková, L Kopkan, Z Vaňourková, M Táborský, A Nishiyama, S H Hwang, B D Hammock, J Sadowski, V Melenovský, J D Imig, L Červenka
We showed recently that increasing kidney epoxyeicosatrienoic acids (EETs) by blocking soluble epoxide hydrolase (sEH), an enzyme responsible for EETs degradation, retarded the development of renal dysfunction and progression of aorto-caval fistula(ACF)-induced congestive heart failure (CHF) in Ren-2 transgenic hypertensive rats (TGR). In that study the final survival rate of untreated ACF TGR was only 14 % but increased to 41 % after sEH blockade. Here we examined if sEH inhibition added to renin-angiotensin system (RAS) blockade would further enhance protection against ACF-induced CHF in TGR...
March 12, 2018: Physiological Research
Eun Hui Bae, In Jin Kim, Hong Sang Choi, Ha Yeon Kim, Chang Seong Kim, Seong Kwon Ma, In S Kim, Soo Wan Kim
Tumor necrosis factor-α (TNFα) and the angiotensin system are involved in inflammatory diseases and may contribute to acute kidney injury. We investigated the mechanisms by which TNFα-converting enzyme (TACE) contributes to lipopolysaccharide (LPS)-induced renal inflammation and the effect of TACE inhibitor treatment on LPS-induced cellular injury in human renal proximal tubule epithelial (HK-2) cells. Mice were treated with LPS (10 mg/kg, i.p.) and HK-2 cells were cultured with or without LPS (10 µg/ml) in the presence or absence of a type 1 TACE inhibitor (1 µM) or type 2 TACE inhibitor (10 µM)...
March 2018: Korean Journal of Physiology & Pharmacology
Peng Wu, Zhong-Xiuzi Gao, Xin-Peng Duan, Xiao-Tong Su, Ming-Xiao Wang, Dao-Hong Lin, Ruimin Gu, Wen-Hui Wang
AT2R (AngII [angiotensin II] type 2 receptor) is expressed in the distal nephrons. The aim of the present study is to examine whether AT2R regulates NCC (Na-Cl cotransporter) and Kir4.1 of the distal convoluted tubule. AngII inhibited the basolateral 40 pS K channel (a Kir4.1/5.1 heterotetramer) in the distal convoluted tubule treated with losartan but not with PD123319. AT2R agonist also inhibits the K channel, indicating that AT2R was involved in tonic regulation of Kir4.1. The infusion of PD123319 stimulated the expression of tNCC (total NCC) and pNCC (phosphorylated NCC; Thr53 ) by a time-dependent way with the peak at 4 days...
February 26, 2018: Hypertension
Qiong Ling, Yu Gu, Jiaxin Chen, Yansheng Chen, Yongyong Shi, Gaofeng Zhao, Qianqian Zhu
BACKGROUND: Patients who use angiotensin-converting enzyme inhibitors (ACEIs)/angiotensin II receptor blockers (ARBs) are prone to developing side effects like hypotension and even refractory hypotension during anesthesia use, and whether ACEIs/ARBs should be continued or discontinued in such patients remains debatable. The present systematic review and meta-analysis was conducted to clarify the consequences of continuing or withholding these drugs, especially with regards to the incidence of intraoperative hypotension, in patients who continue to use ACEIs/ARBs on the day of their scheduled surgery...
February 26, 2018: BMC Anesthesiology
Swapnil Hiremath, Jeanne Françoise Kayibanda, Benjamin J W Chow, Dean Fergusson, Greg A Knoll, Wael Shabana, Brianna Lahey, Olivia McBride, Alexandra Davis, Ayub Akbari
BACKGROUND: Contrast-induced acute kidney injury (CI-AKI) is defined as worsening of renal function after the administration of iodinated contrast material. In patients with cardiovascular disease, kidney disease, and/or diabetes, renin-angiotensin system blockers, non-steroidal anti-inflammatory drugs, diuretics, and metformin can increase the risk of CI-AKI when undergoing contrast imaging. Despite CI-AKI being the leading iatrogenic cause of acute kidney injury, there is a lack of sufficient scientific evidence supporting which drugs should be stopped, when they should be stopped, and when they should be resumed...
February 21, 2018: Systematic Reviews
Xiangbo Gou, Wenying Wang, Sihao Zou, Yajuan Qi, Yanfang Xu
The slowly activating delayed rectifier K+ current (IKs ) is one of the main repolarizing currents in the human heart. Evidence has shown that angiotensin II (Ang II) regulates IKs through the protein kinase C (PKC) pathway, but the related results are controversial. This study was designed to identify PKC isoenzymes involved in the regulation of IKs by Ang II and the underlying molecular mechanism. The whole-cell patch-clamp technique was used to record IKs in isolated guinea pig ventricular cardiomyocytes and in human embryonic kidney (HEK) 293 cells co-transfected with human KCNQ1/KCNE1 genes and Ang II type 1 receptor genes...
February 13, 2018: Journal of Molecular and Cellular Cardiology
Kee Hwan Yoo, Hyung Eun Yim, Eun Soo Bae, Young Sook Hong
Proper and timely assembly of the kidney vasculature with their respective nephrons is crucial during normal kidney development. In this study, we investigated the effects of enalapril (angiotensin-converting enzyme inhibitor) on angiogenesis-related gene expression and microvascular endothelium related to glomeular and tubular changes in the neonatal rat kidney. Enalapril-treated rats had higher tubular injury scores and lower glomerular maturity grades than those of untreated rats. In the enalapril-treated group, intrarenal angiopoietin-2, Tie-2, and thrombospondin-1 protein expression increased, whereas intrarenal angiopoietin-1 protein expression decreased...
February 13, 2018: Journal of Molecular Histology
Lodi C W Roksnoer, Estrellita Uijl, René de Vries, Ingrid M Garrelds, A H Jan Danser
Increasing the degree of renin-angiotensin system (RAS) blockade by combining ≥2 RAS blockers marginally increases efficacy, but results in more side effects. Hence, interference with other systems is currently being investigated, like potentiation of natriuretic peptides with neprilysin inhibitors. However, the neprilysin inhibitor thiorphan was recently found to increase endothelin-1 when administered to TGR(mREN2)27 (Ren2) rats on top of RAS blockade. Here we investigated whether this effect is thiorphan-specific, by comparing the neprilysin inhibitors thiorphan and sacubitril, administered by osmotic minipumps at a low or high dose for 7 days, in Ren2 rats...
February 9, 2018: European Journal of Pharmacology
Luciana Garros Ferreira, Paulo Roberto Barbosa Evora, Verena Kise Capellini, Agnes Afrodite Albuquerque, Marco Túlio Menezes Carvalho, Roseli Aparecida da Silva Gomes, Marco Túlio Parolini, Andrea Carla Celotto
BACKGROUND: In recent years, it has been demonstrated the inhibitory effect of some plant species on the angiotensin-converting enzyme and rosmarinic acid is a prominent constituent of these species. HYPOTHESIS/PURPOSE: This study was carried out to verify the effect of rosmarinic acid on blood pressure through inhibitory activity on angiotensin-converting enzyme in rats. STUDY DESIGN: The arterial hypertension was promoted using 2-kidneys 1-clip model in rats...
January 1, 2018: Phytomedicine: International Journal of Phytotherapy and Phytopharmacology
Jason D Foss, Jessica Fiege, Yoji Shimizu, John P Collister, Tim Mayerhofer, Laurel Wood, John W Osborn
Hypertension is the leading modifiable risk factor for death worldwide, yet the causes remain unclear and treatment remains suboptimal. Catheter-based renal denervation (RDNX) is a promising new treatment for resistant hypertension, but the mechanisms underlying its antihypertensive effect remain unclear. We recently found that RDNX attenuates deoxycorticosterone acetate-salt hypertension and that this is dependent on ablation of afferent renal nerves and is associated with decreased renal inflammation. To determine if this is common to other models of salt-sensitive hypertension, rats underwent complete RDNX (n = 8), selective ablation of afferent renal nerves (n = 8), or sham denervation (n = 8)...
February 2018: Physiological Reports
Hiddo J L Heerspink, Dennis L Andress, George Bakris, John J Brennan, Ricardo Correa-Rotter, Jyotirmoy Dey, Fan-Fan Hou, Dalane W Kitzman, Donald Kohan, Hirofumi Makino, John McMurray, Vlado Perkovic, Sheldon Tobe, Melissa Wigderson, Hans-Henrik Parving, Dick de Zeeuw
AIMS: People with diabetes and chronic kidney disease (CKD) are at high risk for renal events. Recent trials of novel treatments have been negative, possibly because of variability in response to treatment of the target risk factor. Atrasentan is a selective endothelin A receptor antagonist that reduces urinary albumin-to-creatinine ratio (UACR) with a large variability between patients. We are assessing its effect on renal outcomes in the Study of Diabetic Nephropathy with atrasentan (SONAR; NCT01858532) with an enrichment design (>30% lowering of albuminuria) to select patients most likely to benefit...
February 6, 2018: Diabetes, Obesity & Metabolism
Weiwei Cai, Zhenpeng Zhang, Yiqi Huang, Haijian Sun, Liying Qiu
The kidney is an important organ in the regulation of blood pressure, and it is also one of the primary target organs of hypertension. Kidney damage in response to hypertension eventually leads to renal insufficiency. The authors previously demonstrated that vaccarin exhibits a protective role in endothelial injury. However, the effects of vaccarin on the two-kidney, one clip (2K1C) renovascular hypertension model and subsequent kidney injury have yet to be fully elucidated. The present study was designed to investigate the roles and mechanisms of vaccarin in attenuating hypertension and whether vaccarin had beneficial effects on kidney injury...
January 2018: Experimental and Therapeutic Medicine
Yakun Zhao, Qingguo Zhu, Shiping Sun, Yu Qiu, Jingquan Li, Wei Liu, Gangjun Yuan, Hua Ma
Hypertension is one of the most common complications following renal transplantation, and it increases the risk of graft loss and other cardiovascular diseases. Previous studies have revealed that the use of angiotensin II (Ang II) blockers for preventing and treating hypertension is closely associated with higher survival following renal transplantation. However, the cellular and molecular mechanisms by which the vascular contractility of the recipient is altered in response to Ang II following renal transplantation have not been fully elucidated...
January 29, 2018: International Journal of Molecular Medicine
Ming Wang, Dan-Qian Chen, Lin Chen, Hui Zhao, Dan Liu, Zhi-Hao Zhang, Nosratola D Vaziri, Yan Guo, Ying-Yong Zhao, Gang Cao
Renal fibrosis is a common endpoint of the progression of chronic kidney disease (CKD). Suppressing the development and progression of renal fibrosis is essential in the treatment of kidney disease. Our previous study demonstrated that the ethyl acetate extract of the surface layer of Poria cocos exhibited beneficial anti-tubulointerstitial fibrosis. In this study, we isolated new diterpene (PZF) and triterpenes (PZG and PZH) and examined their anti-fibrotic effect. TGF-β1 upregulated the collagen I protein expression in HK-2 cells and PZG and PZH treatment significantly inhibited the upregulated collagen I expression (TGF group 0...
January 31, 2018: Journal of Agricultural and Food Chemistry
Caryl Hollmann, Nicole L Fernandes, Bruce M Biccard
BACKGROUND: The global rate of major noncardiac surgical procedures is increasing annually, and of those patients presenting for surgery, increasing numbers are taking either an angiotensin-converting enzyme inhibitor (ACE-I) or an angiotensin receptor blocker (ARB). The current recommendations of whether to continue or withhold ACE-I and ARB in the perioperative period are conflicting. Previous meta-analyses have linked preoperative ACE-I/ARB therapy to the increased incidence of postinduction hypotension; however, they have failed to correlate this with adverse patient outcomes...
January 29, 2018: Anesthesia and Analgesia
Arkadiusz Lubas, Grzegorz Kade, Marek Saracyn, Stanisław Niemczyk, Przemysław Dyrla
PURPOSE: Renal cortical perfusion measured in noninvasive, dynamic ultrasonic method is connected with the hemodynamic cardiac properties and renal function. Antihypertensive drugs affect the functioning of the heart and kidneys. The aim of the study was to evaluate the effect of a chronic use of antihypertensive drugs on ultrasound parameters of renal cortical perfusion. METHODS: The study included 56 consecutive patients (49 M + 7 F, age 54.0 ± 13.3) with stable chronic kidney disease and hypertension...
January 27, 2018: International Urology and Nephrology
J Albert Abrie, Wessel J A Moolman, Gyles E Cozier, Sylva L Schwager, K Ravi Acharya, Edward D Sturrock
Angiotensin-converting enzyme (ACE) plays a central role in the renin-angiotensin system (RAS), which is primarily responsible for blood pressure homeostasis. Studies have shown that ACE inhibitors yield cardiovascular benefits that cannot be entirely attributed to the inhibition of ACE catalytic activity. It is possible that these benefits are due to interactions between ACE and RAS receptors that mediate the protective arm of the RAS, such as the angiotensin-II receptor type 2 (AT2R) and the receptor MAS...
January 25, 2018: Molecular Pharmacology
Bertram Pitt, David A Bushinsky, Dalane W Kitzman, Frank Ruschitzka, Marco Metra, Gerasimos Filippatos, Patrick Rossignol, Charles Du Mond, Dahlia Garza, Lance Berman, Mitja Lainscak
AIMS: Hyperkalaemia risk precludes optimal renin-angiotensin-aldosterone system inhibitor use in patients with heart failure (HF), particularly those with chronic kidney disease (CKD). Patiromer is a sodium-free, non-absorbed potassium (K+ )-binding polymer approved for the treatment of hyperkalaemia. In PEARL-HF, patiromer 25.2 g (fixed dose) prevented hyperkalaemia in HF patients with or without CKD initiating spironolactone. The current study evaluated the effectiveness of a lower starting dose of patiromer (16...
January 25, 2018: ESC Heart Failure
Eugenia Mata-Greenwood, Arlin B Blood, LeeAnna D Sands, Shannon L Bragg, Daliao Xiao, Lubo Zhang
Brown Norway (BN) and Lewis (LW) inbred rat strains harbor different angiotensin converting enzyme (Ace) polymorphisms that result in higher ACE activity in BN than LW rats. Thus, we hypothesized that pregnant BN rats would show pregnancy complications linked to angiotensin II activity. We performed longitudinal and cross-sectional studies in pregnant LW and BN rats. We found that BN rats have significantly higher ACE activity and angiotensin II levels at pre-pregnancy and throughout pregnancy compared to LW rats, except at mid-gestation...
January 23, 2018: American Journal of Physiology. Endocrinology and Metabolism
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