scholarly journals Connexins and the kidney

2010 ◽  
Vol 298 (5) ◽  
pp. R1143-R1155 ◽  
Author(s):  
Fiona Hanner ◽  
Charlotte Mehlin Sorensen ◽  
Niels-Henrik Holstein-Rathlou ◽  
János Peti-Peterdi
Keyword(s):  
Gap Junctions ◽  
Purinergic Signaling ◽  
Renin Angiotensin System ◽  
Juxtaglomerular Apparatus ◽  
Tubuloglomerular Feedback ◽  
Current Evidence ◽  
Morphological Evidence ◽  
Renal Vasculature ◽  
Angiotensin System ◽  
Major Function

Connexins (Cxs) are widely-expressed proteins that form gap junctions in most organs, including the kidney. In the renal vasculature, Cx37, Cx40, Cx43, and Cx45 are expressed, with predominant expression of Cx40 in the endothelial cells and Cx45 in the vascular smooth muscle cells. In the tubules, there is morphological evidence for the presence of gap junction plaques only in the proximal tubules. In the distal nephron, Cx30, Cx30.3, and Cx37 are expressed, but it is not known whether they form gap junctions connecting neighboring cells or whether they primarily act as hemichannels. As in other systems, the major function of Cxs in the kidney appears to be intercellular communication, although they may also form hemichannels that allow cellular secretion of large signaling molecules. Renal Cxs facilitate vascular conduction, juxtaglomerular apparatus calcium signaling, and tubular purinergic signaling. Accordingly, current evidence points to roles for these Cxs in several important regulatory mechanisms in the kidney, including the renin angiotensin system, tubuloglomerular feedback, and salt and water reabsorption. At the systemic level, renal Cxs may help regulate blood pressure and may be involved in hypertension and diabetes.

Effect of endogenous angiotensin II on the frequency response of the renal vasculature

2004 ◽  
Vol 287 (6) ◽  
pp. F1171-F1178 ◽  
Author(s):  
Gerald F. DiBona ◽  
Linda L. Sawin
Keyword(s):  
Angiotensin Ii ◽  
Frequency Response ◽  
Renin Angiotensin System ◽  
Tubuloglomerular Feedback ◽  
Renal Vasculature ◽  
Renal Nerve ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
High Sodium ◽  
Sodium Diet

The renal vasculature functions as an efficient low-pass filter of the multiple frequencies contained within renal sympathetic nerve activity. This study examined the effect of angiotensin II on the frequency response of the renal vasculature. Physiological changes in the activity of the endogenous renin-angiotensin system were produced by alterations in dietary sodium intake. The frequency response of the renal vasculature was evaluated using pseudorandom binary sequence renal nerve stimulation, and the role of angiotensin II was evaluated by the administration of the angiotensin II AT1-receptor antagonist losartan. In low-sodium-diet rats with increased renin-angiotensin system activity, losartan steepened the renal vascular frequency response (i.e., greater attenuation); this was not seen in normal- or high-sodium-diet rats with normal or decreased renin-angiotensin system activity. Analysis of the transfer function from arterial pressure to renal blood flow, i.e., dynamic autoregulation, showed that the tubuloglomerular feedback but not the myogenic component was enhanced in low- and normal- but not in high-sodium-diet rats and that this was reversed by losartan administration. Thus physiological increases in endogenous renin-angiotensin activity inhibit the renal vascular frequency response to renal nerve stimulation while selectively enhancing the tubuloglomerular feedback component of dynamic autoregulation of renal blood flow.

scholarly journals The cortical collecting duct plays a pivotal role in kidney local renin-angiotensin system

2013 ◽  
Vol 154 (17) ◽  
pp. 643-649 ◽  
Author(s):  
Rózsa Csohány ◽  
Ágnes Prókai ◽  
Anna Kosik ◽  
J. Attila Szabó
Keyword(s):  
Animal Studies ◽  
Collecting Duct ◽  
Renin Angiotensin System ◽  
Juxtaglomerular Apparatus ◽  
Systemic Circulation ◽  
The Body ◽  
Signal Pathways ◽  
Cortical Collecting Duct ◽  
Angiotensin System ◽  
Renin Angiotensin

The renin-angiotensin system is one of the most important hormone systems in the body, and the regulations as well as the role in the juxtaglomerular apparatus are well known. The present review focuses on renin secretion in a recently described localization, the cortical collecting duct. The authors display it in parallel of the copying strategy of an adult and a developing kidney. Furthermore, based on different animal studies it highlights the local role of renin released from the collecting duct. In chronic angiotensin II-infused, 2-kidney, 1-clip hypertensive model as well as in diabetic rats the major source of (pro)renin is indeed the collecting duct. In this localization this hormone can reach both the systemic circulation and the interstitial renin-angiotensin system components including the newly described (pro)renin receptor, by which (pro)renin is able to locally activate pro-fibrotic intracellular signal pathways. Consequently, one can postulate that in the future renin may serve either as a new therapeutic target in nephropathy associated with both hypertension and diabetes or as an early diagnostic marker in chronic diseases leading to nephropathy. Orv. Hetil., 2013, 154, 643–649.

scholarly journals A gap junction inhibitor, carbenoxolone, induces spatiotemporal dispersion of renal cortical perfusion and impairs autoregulation

2016 ◽  
Vol 311 (3) ◽  
pp. H582-H591 ◽  
Author(s):  
Nicholas Mitrou ◽  
Branko Braam ◽  
William A. Cupples
Keyword(s):  
Gap Junctions ◽  
Spatial Variation ◽  
Gap Junction ◽  
Laser Speckle ◽  
Tubuloglomerular Feedback ◽  
Spatial And Temporal Variation ◽  
Contrast Imaging ◽  
Renal Vasculature ◽  
Renal Autoregulation ◽  
Gap Junction Inhibitor

Renal autoregulation dynamics originating from the myogenic response (MR) and tubuloglomerular feedback (TGF) can synchronize over large regions of the kidney surface, likely through gap junction-mediated electrotonic conduction and reflecting distributed operation of autoregulation. We tested the hypotheses that inhibition of gap junctions reduces spatial synchronization of autoregulation dynamics, abrogates spatial and temporal smoothing of renal perfusion, and impairs renal autoregulation. In male Long-Evans rats, we infused the gap junction inhibitor carbenoxolone (CBX) or the related glycyrrhizic acid (GZA) that does not block gap junctions into the renal artery and monitored renal blood flow (RBF) and surface perfusion by laser speckle contrast imaging. Neither CBX nor GZA altered RBF or mean surface perfusion. CBX preferentially increased spatial and temporal variation in the distribution of surface perfusion, increased spatial variation in the operating frequencies of the MR and TGF, and reduced phase coherence of TGF and increased its dispersion. CBX, but not GZA, impaired dynamic and steady-state autoregulation. Separately, infusion of the Rho kinase inhibitor Y-27632 paralyzed smooth muscle, grossly impaired dynamic autoregulation, and monotonically increased spatial variation of surface perfusion. These data suggest CBX inhibited gap junction communication, which in turn reduced the ability of TGF to synchronize among groups of nephrons. The results indicate that impaired autoregulation resulted from degraded synchronization, rather than the reverse. We show that network behavior in the renal vasculature is necessary for effective RBF autoregulation.

Angiotensin II receptor blockade corrects altered expression of gap junctions in vascular endothelial cells from hypertensive rats

2004 ◽  
Vol 287 (1) ◽  
pp. H216-H224 ◽  
Author(s):  
Yasuo Kansui ◽  
Koji Fujii ◽  
Keiichiro Nakamura ◽  
Kenichi Goto ◽  
Hideyuki Oniki ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Endothelial Cells ◽  
Angiotensin Ii ◽  
Gap Junctions ◽  
Vascular Endothelial Cells ◽  
Renin Angiotensin System ◽  
Vascular Endothelial ◽  
Hypertensive Rats ◽  
Angiotensin System ◽  
Renin Angiotensin

Blockade of the renin-angiotensin system improves the impaired endothelium-dependent relaxations associated with hypertension and aging, partly through amelioration of endothelium-derived hyperpolarizing factor (EDHF)-mediated responses. Although the nature of EDHF is still controversial, recent studies have suggested the involvement of gap junctions in EDHF-mediated responses. Gap junctions consist of connexins (Cx), and we therefore tested whether the expression of Cx in vascular endothelial cells would be altered by hypertension and antihypertensive treatment. Spontaneously hypertensive rats (SHR) were treated with either the angiotensin II type 1 receptor antagonist candesartan or the combination of hydralazine and hydrochlorothiazide for 3 mo from 5 to 8 mo of age. Confocal laser scanning microscopy after immunofluorescent labeling with antibodies against Cx37, Cx40, and Cx43 revealed that the expression of Cx37 and Cx40 in endothelial cells of the mesenteric artery was significantly lower in SHR than in WKY. Treatment with candesartan, but not the combination of hydralazine and hydrochlorothiazide, significantly increased the expression of Cx37 and Cx40, although blood pressure decreased similarly. On the other hand, the expression of Cx43, though scarce and heterogeneous, was increased in SHR compared with WKY, and candesartan treatment lowered the expression of Cx43. These findings suggest that renin-angiotensin system blockade corrects the decreased expression of Cx37 and Cx40 in arterial endothelial cells of hypertensive rats, partly independently of blood pressure, whereas the expression of Cx43 changed in the opposite direction. It remains to be clarified whether these changes in Cx37 and Cx40 are related to endothelial function, particularly that attributable to EDHF.

Cyclosporine nephrotoxicity: sodium excretion, autoregulation, and angiotensin II

1987 ◽  
Vol 252 (4) ◽  
pp. F733-F742 ◽  
Author(s):  
F. J. Kaskel ◽  
P. Devarajan ◽  
L. A. Arbeit ◽  
J. S. Partin ◽  
L. C. Moore
Keyword(s):  
Sodium Excretion ◽  
Renin Angiotensin System ◽  
Tubuloglomerular Feedback ◽  
Angiotensin System ◽  
Renal Vasoconstriction ◽  
Fluid Delivery ◽  
Cyclosporine Nephrotoxicity ◽  
Blood Pressures ◽  
Renal Vascular ◽  
Pressure Controlled

Cyclosporine-induced nephrotoxicity (CIN) was studied in rats treated for 7 days with cyclosporine (10 mg x kg-1 x day-1 im) or vehicle (CON). CIN rats displayed characteristic reductions in glomerular filtration (GFR) and renal blood blood flow (RBF), and electron microscopy showed injury to proximal cells. Metabolic studies (7 day) showed significantly lower renal sodium excretion in conscious CIN rats compared with CON. In anesthetized rats at similar blood pressures, nephron GFR (SNGFR) was lower in CIN than CON, but fractional Na reabsorption was similar. In CIN, SNGFR, measured proximally to block flow to the sensing site of tubuloglomerular feedback (TGF) at the macula densa, was not significantly different than distal SNGFR. The rate of distal fluid delivery was significantly lower in CIN than in CON. Inhibition of the renin-angiotensin system (RAS) with captopril (CAP, 10 mg/kg iv), or saralasin (SAR, 0.3 mg x kg-1 x h-1 iv) caused marked arterial hypotension in CIN and a fall in renal vascular resistance (RVR). With arterial pressure controlled, CAP or SAR increased GFR and RBF, and reduced RVR in CIN, but did not reverse the renal deficits compared with similarly treated CON. RBF autoregulation in CIN was impaired between 90 and 140 mmHg but was partially restored by CAP. We conclude that both the filtered load and excretion rate of sodium in CIN are significantly reduced compared with controls, that SNGFR in CIN is not depressed by TGF in response to elevated distal fluid delivery, and that the RAS is not a primarily mediator of the renal vasoconstriction in CIN.

scholarly journals Effect of Estrogen upon the Juxtaglomerular Apparatus and the Renin-Angiotensin System in Rats

1978 ◽  
Vol 126 (3) ◽  
pp. 267-272
Author(s):  
KAZUOKI KONDO ◽  
JIRO MISUMI ◽  
RYUICHI NAKAMURA ◽  
IKUO SAITO ◽  
TAKAO SARUTA
Keyword(s):  
Renin Angiotensin System ◽  
Juxtaglomerular Apparatus ◽  
Angiotensin System ◽  
Renin Angiotensin

scholarly journals A perspective on the use of polyphenols nano-formulation as a nutritional strategy to manage the symptoms of the infected patient with COVID-19

2021 ◽  
Vol 10 (13) ◽  
pp. e400101321471
Author(s):  
Gustavo Vieira de Oliveira ◽  
Mônica Volino-Souza ◽  
Karen Souza dos Santos ◽  
Yunes Scarpine Malheiros ◽  
Carlos Adam Conte-Júnior ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Inflammatory Response ◽  
Crucial Role ◽  
Infected Patient ◽  
Renin Angiotensin System ◽  
Current Evidence ◽  
Food Technology ◽  
Angiotensin System ◽  
Nutritional Strategy ◽  
Nano Formulation

Coronaviruses disease (COVID-19) vaccines have emerged worldwide to control this illness, albeit they cannot guarantee full effectiveness. Polyphenols possess antioxidant, anti-inflammatory, and antiviral properties, all of which may be effective against COVID-19 symptoms. Since polyphenols exhibit low bioavailability, polyphenols nano-formulation (a food technology) have been utilized in COVID-19 patients. Therefore, the purpose of this review is to discuss the current evidence showing the effects of polyphenols nano-formulation in COVID-19 patients. Two previous studies have demonstrated that polyphenols nano-formulation (particularly curcumin) can alleviate clinical manifestation (fever, tachypnea, myalgia, cough) and improve overall recovery since polyphenols can modulate the inflammatory response, oxidative stress, and upregulate certain proteins involved in the renin-angiotensin system, all which play a crucial role on the symptoms caused by COVID-19.

scholarly journals Comparative Studies of Renin-Null Zebrafish and Mice Provide New Functional Insights

Hypertension ◽  
2022 ◽  
Author(s):  
Scott Hoffmann ◽  
Linda Mullins ◽  
Sebastien Rider ◽  
Cara Brown ◽  
Charlotte B. Buckley ◽  
...  
Keyword(s):  
Cell Function ◽  
Smooth Muscle Actin ◽  
Larval Growth ◽  
Renin Angiotensin System ◽  
Sequencing Analysis ◽  
Renal Vasculature ◽  
Exon 2 ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Larval Stages

Background: The renin-angiotensin system is highly conserved across vertebrates, including zebrafish, which possess orthologous genes coding for renin-angiotensin system proteins, and specialized mural cells of the kidney arterioles, capable of synthesising and secreting renin. Methods: We generated zebrafish with CRISPR-Cas9-targeted knockout of renin ( ren −/− ) to investigate renin function in a low blood pressure environment. We used single-cell (10×) RNA sequencing analysis to compare the transcriptome profiles of renin lineage cells from mesonephric kidneys of ren −/− with ren +/+ zebrafish and with the metanephric kidneys of Ren1 c−/− and Ren1 c +/+ mice. Results: The ren −/− larvae exhibited delays in larval growth, glomerular fusion and appearance of a swim bladder, but were viable and withstood low salinity during early larval stages. Optogenetic ablation of renin-expressing cells, located at the anterior mesenteric artery of 3-day-old larvae, caused a loss of tone, due to diminished contractility. The ren −/− mesonephric kidney exhibited vacuolated cells in the proximal tubule, which were also observed in Ren1 c−/− mouse kidney. Fluorescent reporters for renin and smooth muscle actin ( tg(ren:LifeAct-RFP; acta2:EGFP )), revealed a dramatic recruitment of renin lineage cells along the renal vasculature of adult ren −/− fish, suggesting a continued requirement for renin, in the absence of detectable angiotensin metabolites, as seen in the Ren1 YFP Ren1 c−/− mouse. Both phenotypes were rescued by alleles lacking the potential for glycosylation at exon 2, suggesting that glycosylation is not essential for normal physiological function. Conclusions: Phenotypic similarities and transcriptional variations between mouse and zebrafish renin knockouts suggests evolution of renin cell function with terrestrial survival.

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