Angiotensin II regulates V2 receptor and pAQP2 during ureteral obstruction

2009 ◽  
Vol 296 (1) ◽  
pp. F127-F134 ◽  
Author(s):  
Anja M. Jensen ◽  
Eun Hui Bae ◽  
Robert A. Fenton ◽  
Rikke Nørregaard ◽  
Søren Nielsen ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Sodium Fluoride ◽  
Ureteral Obstruction ◽  
At1 Receptor ◽  
Receptor Blockade ◽  
Receptor Complex ◽  
Camp Generation ◽  
Outer Stripe ◽  
V2 Receptor

Release of bilateral ureteral obstruction (BUO) is associated with nephrogenic diabetes insipidus (NDI) and a reduced abundance of the vasopressin-regulated aquaporins. To evaluate the role of the vasopressin type 2 receptor (V2R), we determined V2R abundance in kidneys from rats subjected to 24-h BUO or 24-h unilateral ureteral obstruction (UUO) followed by 48-h release. Because angiotensin II type 1 (AT1) receptor blockade attenuates postobstructive polyuria and aquaporin-2 (AQP2) downregulation, we examined the effect of AT1 receptor blockade on AQP2 phosphorylated at serine 256 (pS256-AQP2) and V2 receptor complex abundance in kidney inner medulla (IM). Furthermore, cAMP generation in sodium fluoride- and forskolin-stimulated inner medullary membrane fractions was studied after release of BUO. V2R was significantly reduced to 12% of sham levels in IM and to 52% of sham levels in cortex and outer stripe of outer medulla (OSOM) from BUO rats. In UUO rats, V2R abundance in the obstructed kidney IM decreased to 35% of sham levels, whereas it was comparable to sham levels in the nonobstructed kidney IM. No significant change was observed in cortex and OSOM. AT1 receptor blockade attenuated V2R, pS256-AQP2, and Gsα protein downregulation in IM and partially reversed the obstruction-induced inhibition of sodium fluoride- and forskolin-stimulated cAMP generation in inner medullary membrane fractions from BUO rats. In conclusion, V2R downregulation plays a pivotal role in development of NDI after release of BUO. In addition, we have shown that angiotensin II regulates the V2 receptor complex and pS256-AQP2 in postobstructive kidney IM, probably by stimulating cAMP generation.

ACE2/Angiotensin-(1-7)/Mas Receptor Axis in Human Cancer: Potential Role for Pediatric Tumors

2020 ◽  
Vol 21 (9) ◽  
pp. 892-901 ◽  
Author(s):  
Ana Luiza Ataide Carneiro de Paula Gonzaga ◽  
Vitória Andrade Palmeira ◽  
Thomas Felipe Silva Ribeiro ◽  
Larissa Braga Costa ◽  
Karla Emília de Sá Rodrigues ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Angiotensin Ii ◽  
Pediatric Cancer ◽  
Pediatric Patients ◽  
Human Cancer ◽  
Experimental Studies ◽  
At1 Receptor ◽  
Pediatric Tumors ◽  
Mas Receptor

Background: Pediatric tumors remain the highest cause of death in developed countries. Research on novel therapeutic strategies with lesser side effects is of utmost importance. In this scenario, the role of Renin-Angiotensin System (RAS) axes, the classical one formed by angiotensinconverting enzyme (ACE), Angiotensin II and AT1 receptor and the alternative axis composed by ACE2, Angiotensin-(1-7) and Mas receptor, have been investigated in cancer. Objective: This review aimed to summarize the pathophysiological role of RAS in cancer, evidence for anti-tumor effects of ACE2/Angiotensin-(1-7)/Mas receptor axis and future therapeutic perspectives for pediatric cancer. Methods: Pubmed, Scopus and Scielo were searched in regard to RAS molecules in human cancer and pediatric patients. The search terms were “RAS”, “ACE”, “Angiotensin-(1-7)”, “ACE2”, “Angiotensin II”, “AT1 receptor”, “Mas receptor”, “Pediatric”, “Cancer”. Results: Experimental studies have shown that Angiotensin-(1-7) inhibits the growth of tumor cells and reduces local inflammation and angiogenesis in several types of cancer. Clinical trials with Angiotensin-( 1-7) or TXA127, a pharmaceutical grade formulation of the naturally occurring peptide, have reported promising findings, but not enough to recommend medical use in human cancer. In regard to pediatric cancer, only three articles that marginally investigated RAS components were found and none of them evaluated molecules of the alternative RAS axis. Conclusion: Despite the potential applicability of Angiotensin-(1-7) in pediatric tumors, the role of this molecule was never tested. Further clinical trials are necessary, also including pediatric patients, to confirm safety and efficiency and to define therapeutic targets.

scholarly journals Angiotensin Ii Type 1 (at1 ) Receptor Blockade Enhances the L-NAME-Induced Vasoconstriction in Rat Submandibular Gland

2002 ◽  
Vol 87 (3) ◽  
pp. 327-333 ◽  
Author(s):  
J. Vág ◽  
Beáta Kerémi ◽  
Csilla Hably ◽  
J. Bartha ◽  
Á. Fazekas
Keyword(s):  
Angiotensin Ii ◽  
Submandibular Gland ◽  
At1 Receptor ◽  
Receptor Blockade ◽  
Rat Submandibular Gland

Role of Angiotensin II AT1 Receptor Blockers in the Treatment of Arterial Hypertension

2003 ◽  
Vol 10 (6) ◽  
pp. 401-408 ◽  
Author(s):  
Freddy Contreras ◽  
Mar??a Antonia de la Parte ◽  
Julio Cabrera ◽  
Nestor Ospino ◽  
Zafar H. Israili ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Arterial Hypertension ◽  
At1 Receptor ◽  
Receptor Blockers ◽  
At1 Receptor Blockers

scholarly journals Prevention of atherosclerosis by specific AT1-receptor blockade with candesartan cilexetil

2001 ◽  
Vol 2 (1_suppl) ◽  
pp. S77-S80
Author(s):  
Vasilios Papademetriou ◽  
Philippe Mammillot ◽  
Robert Redman ◽  
Aldo Notargiacomo ◽  
Puneet Narayan ◽  
...  
Keyword(s):  
At1 Receptor ◽  
Receptor Blockade ◽  
Dependent Manner ◽  
Vascular Events ◽  
Oxidised Ldl ◽  
Atherosclerotic Plaque Formation ◽  
Maximum Inhibition ◽  
Prevention Of Atherosclerosis ◽  
Dose Dependent

Several studies indicate that blockade of the renin-angiotensin-aldosterone system (RAAS) can prevent atherosclerosis and vascular events, but the precise mechanisms involved are still unclear. In this study, we investigated the effect of the AT 1-receptor blocker, candesartan, in the prevention of atherosclerosis in Watanabe heritable hyperlipidaemic (WHHL) rabbits and also the effect of AT1-receptor blockade in the uptake of oxidised LDL by macrophage cell cultures. In the first set of experiments, 12 WHHL rabbits were randomly assigned to three groups: placebo, atenolol 5 mg/kg daily or candesartan 2 mg/kg daily for six months. Compared with controls and atenolol-treated rabbits, candesartan treatment resulted in a significant 50—60% reduction of atherosclerotic plaque formation and a 66% reduction in cholesterol accumulation in the thoracic aorta. Studies in macrophage cultures indicated that candesartan prevented uptake of oxidised LDL-(oxLDL)-cholesterol by cultured macrophages. Candesartan inhibited the uptake of oxLDL in a dose-dependent manner, reaching a maximum inhibition of 70% at concentrations of 5.6 µg/ml. Further studies in other animal models and well-designed trials in humans are warranted to further explore the role of AT1-receptor blockade in the prevention of atherosclerosis.

scholarly journals Impaired Vascular Contractility and Aortic Wall Degeneration in Fibulin-4 Deficient Mice: Effect of Angiotensin II Type 1 (AT1) Receptor Blockade

PLoS ONE ◽  
2011 ◽  
Vol 6 (8) ◽  
pp. e23411 ◽  
Author(s):  
Els Moltzer ◽  
Luuk te Riet ◽  
Sigrid M. A. Swagemakers ◽  
Paula M. van Heijningen ◽  
Marcel Vermeij ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Aortic Wall ◽  
At1 Receptor ◽  
Receptor Blockade ◽  
Vascular Contractility ◽  
Deficient Mice

scholarly journals Renin–angiotensin–aldosterone system blockade with telmisartan prevents the decline in cardiac contractility orchiectomy-dependent in SHR: role of PPAR-γ activation

2021 ◽  
Author(s):  
Marito Afonso Sousa Costa Silva ◽  
Camila Almenara ◽  
Antonio Marcos Birocale ◽  
Renata Andrade Ávila ◽  
Ivanita Stefanon ◽  
...  
Keyword(s):  
Cardiac Contractility ◽  
Renin Angiotensin System ◽  
At1 Receptor ◽  
Control Group ◽  
Receptor Blockade ◽  
Testosterone Deficiency ◽  
Renin Angiotensin ◽  
Ppar Γ ◽  
Cardiac Contractile

Abstract The present study aimed to investigate the beneficial role of AT1 receptor blockade and PPAR-γ activation in preventing cardiac contractile changes in hypertensive animals (SHR) with testosterone deficiency. Rats were divided into a control group (sham), orchiectomized (OCT), orchiectomized that received telmisartan (OCT + Tel) or telmisartan plus PPAR-γ antagonist (OCT + Tel + BADGE). After 8 weeks, contractility of isolated papillary muscles was evaluated. The OCT group showed a reduction in the contraction force, avoided in the OCT + Tel and Tel + BADGE groups. Post-pause potentiation (PPP) was similar in the Sham, OCT and OCT + Tel group, suggesting prevention of sarcoplasmic reticulum activity. In contrast, PPP in the OCT + Tel + BADGE group decreased. The reduction in response to calcium or isoproterenol in the OCT group was prevented in the OCT + Tel and Tel + BADGE group. The influx of calcium, assessed indirectly, although it was similar in the OCT and Sham groups, increased both in the OCT + Tel groups and in the OCT + Tel + BADGE groups. SERCA2a protein expression was increased in the OCT group, which was avoided in the OCT + Tel and Tel + BADGE group. NCX expression was increased in the Tel + BADGE group compared to OCT + Tel and sham. Our results suggest that AT1 receptor blockade with telmisartan prevents compromised papillary muscle contractility in SHR. Moreover, it has been shown that the activation of PPAR-γ adds benefits to the inhibition of renin-angiotensin system with telmisartan in preventing harmful effects on the contractility of hypertensive rats with testosterone deficiency.

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