Interaction of the renin angiotensin and cox systems in the kidney

Quadri, Syed; Culver, Silas A; Li, Caixia; Siragy, Helmy M.

doi:10.2741/s459

Cited by 23 publications

(14 citation statements)

References 81 publications

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“…Experimental and clinical studies have provided evidence for the inhibition of renin secretion by a high sodium intake [ 16 , 17 ]. Besides, Ang II inhibits renin release directly in a short negative feedback loop by means of the AT1 receptors (AT1R), and indirectly through a suppression of prostanoid synthesis induced by cyclooxygenase-2 (COX-2) [ 18 •]. The role of AVP in the regulation of renin release is more complex as AVP stimulates the release by acting on the V2 receptors (V2R) in the JGA cells.…”

Section: Renin-angiotensin Systemmentioning

confidence: 99%

Dysregulation of the Renin-Angiotensin System and the Vasopressinergic System Interactions in Cardiovascular Disorders

2018

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Purpose of ReviewIn many instances, the renin-angiotensin system (RAS) and the vasopressinergic system (VPS) are jointly activated by the same stimuli and engaged in the regulation of the same processes.Recent FindingsAngiotensin II (Ang II) and arginine vasopressin (AVP), which are the main active compounds of the RAS and the VPS, interact at several levels. Firstly, Ang II, acting on AT1 receptors (AT1R), plays a significant role in the release of AVP from vasopressinergic neurons and AVP, stimulating V1a receptors (V1aR), regulates the release of renin in the kidney. Secondly, Ang II and AVP, acting on AT1R and V1aR, respectively, exert vasoconstriction, increase cardiac contractility, stimulate the sympathoadrenal system, and elevate blood pressure. At the same time, they act antagonistically in the regulation of blood pressure by baroreflex. Thirdly, the cooperative action of Ang II acting on AT1R and AVP stimulating both V1aR and V2 receptors in the kidney is necessary for the appropriate regulation of renal blood flow and the efficient resorption of sodium and water. Furthermore, both peptides enhance the release of aldosterone and potentiate its action in the renal tubules.SummaryIn this review, we (1) point attention to the role of the cooperative action of Ang II and AVP for the regulation of blood pressure and the water-electrolyte balance under physiological conditions, (2) present the subcellular mechanisms underlying interactions of these two peptides, and (3) provide evidence that dysregulation of the cooperative action of Ang II and AVP significantly contributes to the development of disturbances in the regulation of blood pressure and the water-electrolyte balance in cardiovascular diseases.

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Section: Renin-angiotensin Systemmentioning

confidence: 99%

Dysregulation of the Renin-Angiotensin System and the Vasopressinergic System Interactions in Cardiovascular Disorders

2018

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“…COX-2 is mainly expressed in both macula densa cells in the cortex and the thick limb of the ascending loop of Henle and medulla. Cortical COX-2 plays a pivotal role in renin release and subsequent pro-hypertensive effects, while COX-2 in the medullary region contributes to salt and water reabsorption ( 71 ). Accumulated evidence has associated the overexpression of COX-2 with the progression of DN, with COX-2 inhibition reducing hyperfiltration and proteinuria, abrogating Ang II-mediated reductions in GFR, and retarding progressive renal injury ( 72 – 75 ).…”

Section: Discussionmentioning

confidence: 99%

Identification of copper-related biomarkers and potential molecule mechanism in diabetic nephropathy

2022

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BackgroundDiabetic nephropathy (DN) is a chronic microvascular complication in patients with diabetes mellitus, which is the leading cause of end-stage renal disease. However, the role of copper-related genes (CRGs) in DN development remains unclear.Materials and methodsCRGs were acquired from the GeneCards and NCBI databases. Based on the GSE96804 and GSE111154 datasets from the GEO repository, we identified hub CRGs for DN progression by taking the intersection of differentially expressed CRGs (DECRGs) and genes in the key module from Weighted Gene Co-expression Network Analysis. The Maximal Clique Centrality algorithm was used to identify the key CRGs from hub CRGs. Transcriptional factors (TFs) and microRNAs (miRNAs) targeting hub CRGs were acquired from publicly available databases. The CIBERSORT algorithm was used to perform comparative immune cell infiltration analysis between normal and DN samples.ResultsEighty-two DECRGs were identified between normal and DN samples, as were 10 hub CRGs, namely PTGS2, DUSP1, JUN, FOS, S100A8, S100A12, NAIP, CLEC4E, CXCR1, and CXCR2. Thirty-nine TFs and 165 miRNAs potentially targeted these 10 hub CRGs. PTGS2 was identified as the key CRG and FOS as the most significant gene among all of DECRGs. RELA was identified as the hub TF interacting with PTGS2 by taking the intersection of potential TFs from the ChEA and JASPAR public databases. let-7b-5p was identified as the hub miRNA targeting PTGS2 by taking the intersection of miRNAs from the miRwalk, RNA22, RNAInter, TargetMiner, miRTarBase, and ENCORI databases. Similarly, CREB1, E2F1, and RELA were revealed as hub TFs for FOS, and miR-338-3p as the hub miRNA. Finally, compared with those in healthy samples, there are more infiltrating memory B cells, M1 macrophages, M2 macrophages, and resting mast cells and fewer infiltrating activated mast cells and neutrophils in DN samples (all p< 0.05).ConclusionThe 10 identified hub copper-related genes provide insight into the mechanisms of DN development. It is beneficial to examine and understand the interaction between hub CRGs and potential regulatory molecules in DN. This knowledge may provide a novel theoretical foundation for the development of diagnostic biomarkers and copper-related therapy targets in DN.

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“…Both type 1 and type 2 cyclooxygenase (COX) are identified in renal Af-arts (22,36). Prostaglandins (PGs) generated by the COX have been implicated in modulation of ANG II-induced Af-Art vasoconstriction (30,80). Inhibition or knockout of COX2 augments the pressor effect of ANG II (48,79).…”

Section: Discussionmentioning

confidence: 99%

Enhanced hemodynamic responses to angiotensin II in diabetes are associated with increased expression and activity of AT1 receptors in the afferent arteriole

Zhang

Song

et al. 2017

Physiological Genomics

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The prevalence of hypertension is about twofold higher in diabetic than in nondiabetic subjects. Hypertension aggravates the progression of diabetic complications, especially diabetic nephropathy. However, the mechanisms for the development of hypertension in diabetes have not been elucidated. We hypothesized that enhanced constrictive responsiveness of renal afferent arterioles (Af-Art) to angiotensin II (ANG II) mediated by ANG II type 1 (AT1) receptors contributes to the development of hypertension in diabetes. In response to an acute bolus intravenous injection of ANG II, alloxan-induced diabetic mice exhibited a higher mean arterial pressure (MAP) (119.1 ± 3.8 vs. 106.2 ± 3.5 mmHg) and a lower renal blood flow (0.25 ± 0.07 vs. 0.52 ± 0.14 ml/min) compared with nondiabetic mice. In response to chronic ANG II infusion, the MAP measured with telemetry increased by 55.8 ± 6.5 mmHg in diabetic mice, but only by 32.3 ± 3.8 mmHg in nondiabetic mice. The mRNA level of AT1 receptor increased by ~10-fold in isolated Af-Art of diabetic mice compared with nondiabetic mice, whereas ANG II type 2 (AT2) receptor expression did not change. The ANG II dose-response curve of the Af-Art was significantly enhanced in diabetic mice. Moreover, the AT1 receptor antagonist, losartan, blocked the ANG II-induced vasoconstriction in both diabetic mice and nondiabetic mice. In conclusion, we found enhanced expression of the AT1 receptor and exaggerated response to ANG II of the Af-Art in diabetes, which may contribute to the increased prevalence of hypertension in diabetes.

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Interaction of the renin angiotensin and cox systems in the kidney

Cited by 23 publications

References 81 publications

Dysregulation of the Renin-Angiotensin System and the Vasopressinergic System Interactions in Cardiovascular Disorders

Dysregulation of the Renin-Angiotensin System and the Vasopressinergic System Interactions in Cardiovascular Disorders

Identification of copper-related biomarkers and potential molecule mechanism in diabetic nephropathy

Enhanced hemodynamic responses to angiotensin II in diabetes are associated with increased expression and activity of AT1 receptors in the afferent arteriole

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