scholarly journals TRPV1 protects renal ischemia-reperfusion injury in diet-induced obese mice by enhancing CGRP release and increasing renal blood flow

PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e6505 ◽  
Author(s):  
Beihua Zhong ◽  
Shuangtao Ma ◽  
Donna H. Wang
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion ◽  
Fasting Blood Glucose ◽  
Western Diet ◽  
Renal Ischemia ◽  
Mouse Strains ◽  
Transient Receptor Potential Vanilloid ◽  
Cgrp Release

Background Obesity is a major risk factor for end-stage renal disease. Using transient receptor potential vanilloid 1 knockout (TRPV1−/−) mice, we tested the hypothesis that TRPV1 protects against obesity-induced exacerbation of renal ischemia-reperfusion (I/R) injury. Methods TRPV1−/− and wild-type (WT) mice were fed a chow or Western diet (WD) for 22–23 weeks. After that, mice were subjected to renal I/R injury, and renal cortical blood flow (CBF) and medullary blood flow (MBF) were measured. Results The Western diet significantly increased body weight and fasting blood glucose levels in both TRPV1−/− and WT mice. WD-induced impairment of glucose tolerance was worsened in TRPV1−/− mice compared with WT mice. WD intake prolonged the time required to reach peak reperfusion in the cortex and medulla (both P < 0.05), decreased the recovery rate of CBF (P < 0.05) and MBF (P < 0.05), and increased blood urea nitrogen, plasma creatinine, and urinary 8-isoprostane levels after I/R in both mouse strains, with greater effects in TRPV1−/− mice (all P < 0.05). Renal I/R increased calcitonin gene-related peptide (CGRP) release in WT but not in TRPV1−/− mice, and WD attenuated CGRP release in WT mice. Moreover, blockade of CGRP receptors impaired renal regional blood flow and renal function in renal I/R injured WT mice. Conclusion These results indicate that TRPV1 plays a protective role in WD-induced exacerbation of renal I/R injury probably through enhancing CGRP release and increasing renal blood flow.

scholarly journals Gender Difference in Renal Blood Flow Response to Angiotensin II Administration after Ischemia/Reperfusion in Rats: The Role of AT2 Receptor

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Maryam Maleki ◽  
Mehdi Nematbakhsh
Keyword(s):  
Blood Flow ◽  
Angiotensin Ii ◽  
Renal Blood Flow ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Female Rats ◽  
Male Rats ◽  
Ang Ii ◽  
The Impact

Background. Renal ischemia/reperfusion (I/R) is one of the major causes of kidney failure, and it may interact with renin angiotensin system while angiotensin II (Ang II) type 2 receptor (AT2R) expression is gender dependent. We examined the role of AT2R blockade on vascular response to Ang II after I/R in rats.Methods.Male and female rats were subjected to 30 min renal ischemia followed by reperfusion. Two groups of rats received either vehicle or AT2R antagonist, PD123319. Mean arterial pressure (MAP), and renal blood flow (RBF) responses were assessed during graded Ang II (100, 300, and 1000 ng/kg/min, i.v.) infusion at controlled renal perfusion pressure (RPP).Results.Vehicle or antagonist did not alter MAP, RPP, and RBF levels significantly; however, 30 min after reperfusion, RBF decreased insignificantly in female treated with PD123319 (P=0.07). Ang II reduced RBF and increased renal vascular resistance (RVR) in a dose-related fashion (Pdose<0.0001), and PD123319 intensified the reduction of RBF response in female (Pgroup<0.005), but not in male rats.Conclusion.The impact of the AT2R on vascular responses to Ang II in renal I/R injury appears to be sexually dimorphic. PD123319 infusion promotes these hemodynamic responses in female more than in male rats.

scholarly journals Endothelial-Derived miR-17∼92 Promotes Angiogenesis to Protect against Renal Ischemia-Reperfusion Injury

2021 ◽  
Vol 32 (3) ◽  
pp. 553-562
Author(s):  
Takuto Chiba ◽  
Débora M. Cerqueira ◽  
Yao Li ◽  
Andrew J. Bodnar ◽  
Elina Mukherjee ◽  
...  
Keyword(s):  
Endothelial Cells ◽  
Blood Flow ◽  
Reperfusion Injury ◽  
Renal Blood Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Mirna Cluster ◽  
Renal Vasculature ◽  
Renal Ischemia Reperfusion Injury

BackgroundDamage to the renal microvasculature is a hallmark of renal ischemia-reperfusion injury (IRI)–mediated AKI. The miR-17∼92 miRNA cluster (encoding miR-17, -18a, -19a, -20a, -19b-1, and -92a-1) regulates angiogenesis in multiple settings, but no definitive role in renal endothelium during AKI pathogenesis has been established.MethodsAntibodies bound to magnetic beads were utilized to selectively enrich for renal endothelial cells from mice. Endothelial-specific miR-17∼92 knockout (miR-17∼92endo−/−) mice were generated and given renal IRI. Mice were monitored for the development of AKI using serum chemistries and histology and for renal blood flow using magnetic resonance imaging (MRI) and laser Doppler imaging. Mice were treated with miRNA mimics during renal IRI, and therapeutic efficacies were evaluated.ResultsmiR-17, -18a, -20a, -19b, and pri–miR-17∼92 are dynamically regulated in renal endothelial cells after renal IRI. miR-17∼92endo−/− exacerbates renal IRI in male and female mice. Specifically, miR-17∼92endo−/− promotes renal tubular injury, reduces renal blood flow, promotes microvascular rarefaction, increases renal oxidative stress, and promotes macrophage infiltration to injured kidneys. The potent antiangiogenic factor thrombospondin 1 (TSP1) is highly expressed in renal endothelium in miR-17∼92endo−/− after renal IRI and is a target of miR-18a and miR-19a/b. miR-17∼92 is critical in the angiogenic response after renal IRI, which treatment with miR-18a and miR-19b mimics can mitigate.ConclusionsThese data suggest that endothelial-derived miR-17∼92 stimulates a reparative response in damaged renal vasculature during renal IRI by regulating angiogenic pathways.

Renal Ischemia – Reperfusion Injury: Contribution of Nitric Oxide and Renal Blood Flow

Nephron ◽  
1998 ◽  
Vol 80 (4) ◽  
pp. 458-467 ◽  
Author(s):  
Elisheva Mashiach ◽  
Shifra Sela ◽  
Josi Winaver ◽  
Shaul M. Shasha ◽  
Batya Kristal
Keyword(s):  
Nitric Oxide ◽  
Blood Flow ◽  
Reperfusion Injury ◽  
Renal Blood Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Renal Ischemia Reperfusion Injury

scholarly journals Knockout of Trpa1 Exacerbates Renal Ischemia–Reperfusion Injury With Classical Activation of Macrophages

2020 ◽  
Author(s):  
Shuangtao Ma ◽  
Donna H Wang
Keyword(s):  
Reperfusion Injury ◽  
Transient Receptor Potential ◽  
Ischemia Reperfusion Injury ◽  
Gene Knockout ◽  
Ischemia Reperfusion ◽  
Renal Ischemia ◽  
Activated Macrophages ◽  
Renal Ischemia Reperfusion Injury ◽  
Classically Activated Macrophages ◽  
Classically Activated

Abstract BACKGROUND Classically activated macrophages contribute to the development of renal ischemia–reperfusion injury (IRI). This study aimed to investigate the role of transient receptor potential ankyrin 1 (Trpa1), a regulator of macrophage activation, in IRI-induced acute kidney injury (AKI) by using the Trpa1 gene knockout (Trpa1−/−) mouse model. METHODS Male 8-week-old Trpa1−/− mice and wild-type (WT) littermates were subjected to renal ischemia for 35 minutes by clamping bilateral renal pedicles under isoflurane anesthesia, and blood and tissue samples were collected 24 hours after reperfusion and analyzed with histological and molecular measurements. RESULTS Following IRI, Trpa1−/− mice developed more deteriorated biochemical and morphological signs of AKI when comparing with WT mice. More classically activated M1 macrophages were found in the kidneys of Trpa1−/− mice comparing with WT mice after IRI, while the counts of alternatively activated M2 macrophages in the kidney were similar between the 2 strains after IRI. Furthermore, significantly higher expression levels of proinflammatory markers including interleukin-1 beta and tumor necrosis factor alpha were detected in the kidney of Trpa1−/− mice compared with WT mice after IRI. The levels of TRPA1 protein in the kidney of WT mice were also decreased after IRI. CONCLUSIONS Our results show that ablation of Trpa1 exacerbates infiltration of classically activated macrophages, renal inflammation, and renal injury in mice after IRI. These findings suggest that activation of TRPA1 may protect against IRI-induced AKI via regulation of macrophage-mediated inflammatory pathway.

P0522INHIBITING 15-PGDH PREVENTS ISCHEMIC RENAL INJURY BY A PGE2/EP4 SIGNALING PATHWAY MEDIATING VASODILATION, INCREASED RENAL BLOOD FLOW, AND INCREASED ADENOSINE/A2A RECEPTOR

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Byeong Woo KIm ◽  
Sun hee Kim ◽  
Ki beom Bae
Keyword(s):  
Blood Flow ◽  
Renal Blood Flow ◽  
Renal Injury ◽  
Ischemia Reperfusion ◽  
Adenosine A2a Receptor ◽  
Vehicle Group ◽  
Control Group ◽  
Protective Effects ◽  
A2a Receptor ◽  
Adenosine A2a

Abstract Background and Aims We demonstrate the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia reperfusion injury (IRI). AKI due to ischemic injury represents a significant clinical problem. Prostaglandin E2 (PGE2) is vasodilator in the kidney, but is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Method 10-week aged male C57/BL6 mice were randomly allocated to five groups (n=8 to 15 in each group): the sham-control group, sham-SW033291 group, IRI-vehicle group, IRI-indomethacin group and the IRI-SW033291 group. IRI were induced by clamping bilateral renal artery for 30 min followed by 24 hours of reperfusion. Vehicle, indomethacin, or SW033291 were intraperitoneally administered three times at 1 hour before, immediately after, and 12 hours after IRI. Renal function, histological changes, and renal blood flow were compared and the relevant parameters of oxidative stress and inflammation were detected. Results Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI histologic injury score and tubular apoptosis and markedly reduced biomarkers of renal injury that included BUN, creatinine, NGAL and KIM-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high mobility group box 1 (HMGB1), and malondialdehyde (MDA). Protective effects of SW033291 were mediated by PGE2 signaling as they could be blocked by pharmacologic inhibition of PGE2 synthesis or of the EP4 type PGE2 receptor. Consistent with activation of PGE2 signaling, SW033291 induced renal levels of both EP4 and of cyclic adenosine monophosphate (cAMP), along with other vasodilatory effectors including AMP, adenosine, and the adenosine A2A receptor (A2A). Protective effects of SW0333291 could largely be achieved with a single prophylactic dose of the drug. Conclusion Inhibiting 15-PGDH may thus represent a novel strategy for prophylaxis of ischemic AKI in multiple clinical settings, including renal transplantation and cardiovascular surgery.

scholarly journals Downstream effects of splanchnic ischemia-reperfusion injury on renal function and eicosanoid release

1997 ◽  
Vol 83 (2) ◽  
pp. 530-536 ◽  
Author(s):  
Patricia Rothenbach ◽  
Richard H. Turnage ◽  
Jose Iglesias ◽  
Angela Riva ◽  
Lori Bartula ◽  
...  
Keyword(s):  
Blood Flow ◽  
Renal Function ◽  
Reperfusion Injury ◽  
Renal Blood Flow ◽  
Ischemia Reperfusion Injury ◽  
Ischemia Reperfusion ◽  
Inulin Clearance ◽  
Downstream Effects ◽  
Splanchnic Ischemia ◽  
Eicosanoid Release

Rothenbach, Patricia, Richard H. Turnage, Jose Iglesias, Angela Riva, Lori Bartula, and Stuart I. Myers. Downstream effects of splanchnic ischemia-reperfusion injury on renal function and eicosanoid release. J. Appl. Physiol.82(2): 530–536, 1997.—This study examines the hypothesis that intestinal ischemia-reperfusion (I/R) injury contributes to renal dysfunction by altered renal eicosanoid release. Anesthetized Sprague-Dawley rats underwent 60 min of sham or superior mesenteric artery (SMA) occlusion with 60 min of reperfusion. The I/R groups received either allopurinol, pentoxifylline, 1-benzylimidazole, or carrier before SMA occlusion. In vivo renal artery blood flow was measured by Transonic flow probes, the kidneys were then perfused in vitro for 30 min, and the effluent was analyzed for eicosanoid release and renal function. Intestinal I/R caused a twofold increase in the ratio of renal release of thromboxane B2to prostaglandin E2and to 6-ketoprostaglandin F1αcompared with the sham level, with a corresponding 25% decrease in renal sodium and inulin clearance and renal blood flow. Pentoxifylline or allopurinol pretreatment restored renal eicosanoid release and renal sodium and inulin clearance to the sham level but did not alter renal blood flow. Pretreatment with 1-benzylimidazole restored renal function, eicosanoid release, and renal blood flow to sham levels. These data suggest that severe intestinal I/R contributes to the downregulation of renal function. The decrease in renal function is due in part to toxic oxygen metabolites, which occur in the milieu of altered renal eicosanoid release, reflecting a decrease in vasodilator and an increase in vasoconstrictor eicosanoids.

Renal blood flow in dogs during diffusion respiration

1959 ◽  
Vol 14 (3) ◽  
pp. 405-410 ◽  
Author(s):  
Joseph E. Stone ◽  
Richard L. Irwin ◽  
Charles D. Wood ◽  
William B. Draper ◽  
Richard W. Whitehead
Keyword(s):  
Carbon Dioxide ◽  
Blood Flow ◽  
Medical Research ◽  
Renal Blood Flow ◽  
Renal Denervation ◽  
Respiratory Arrest ◽  
Renal Ischemia ◽  
Central Effects ◽  
Marked Decline ◽  
Series Of Experiments

Two series of experiments were performed with appropriate controls on dogs in which respiratory arrest was produced and maintained by the injection of an overdose of thiopental or by administration of decamethonium, respectively. Renal blood flow was measured by a modification of the method of Selkurt ( Methods in Medical Research, vol. 1). A marked fall in renal blood flow coincident with apnea and anuria was found to occur consistently with diffusion respiration under thiopental. Both the renal ischemia and the anuria were preventable by renal denervation (pharmacological block). During diffusion respiration experiments in which decamethonium was used to cause and maintain apnea, a marked decline in renal blood flow or urine secretion did not occur during the first 15 minutes of apnea. It is concluded that the prompt onset of anuria in diffusion respiration under thiopental is due to a central synergism between thiopental and endogenous carbon dioxide. Further, it is reasoned that the delayed fall in renal blood flow and attendant anuria which occurred under decamethonium represent the central effects of increasing concentrations of carbon dioxide in the absence of thiopental. Submitted on November 5, 1958

Diet-induced obesity alters dural CGRP release and potentiates TRPA1-mediated trigeminovascular responses

Cephalalgia ◽  
2016 ◽  
Vol 37 (6) ◽  
pp. 581-591 ◽  
Author(s):  
Balázs Marics ◽  
Barna Peitl ◽  
Angelika Varga ◽  
Kitti Pázmándi ◽  
Attila Bácsi ◽  
...  
Keyword(s):  
Protein Expression ◽  
Transient Receptor Potential ◽  
Fasting Blood Glucose ◽  
Receptor Potential ◽  
Primary Headache ◽  
Headache Disorder ◽  
Chemical Exposure ◽  
Receptor Activation ◽  
Trigeminal Ganglia ◽  
Cgrp Release

Background Clinical studies suggest a link between obesity and the primary headache disorder migraine. In our study we aimed to reveal the effect of obesity on meningeal nociceptor function in rats receiving a high-fat, high-sucrose diet. Methods Transient receptor potential ankyrin 1 (TRPA1) receptor activation-induced changes in meningeal blood flow, release of calcitonin gene-related peptide (CGRP) from trigeminal afferents and TRPA1 protein expression in the trigeminal ganglia were measured in control and obese rats. Metabolic parameters of the animals were assessed by measuring glucose and insulin homeostasis as well as plasma cytokine concentrations. Results The present experiments revealed an enhanced basal and TRPA1 receptor agonist-induced CGRP release from meningeal afferents of obese insulin-resistant rats and an attenuated CGRP release to potassium chloride. Obesity was also associated with an augmented vasodilatation in meningeal arteries after dural application of the TRPA1 agonist acrolein, a reduction in TRPA1 protein expression in the trigeminal ganglia and elevations in circulating proinflammatory cytokines IL-1β and IL-6 in addition to increased fasting blood glucose and insulin concentrations. Conclusions Our results suggest trigeminal sensitisation as a mechanism for enhanced headache susceptibility in obese individuals after chemical exposure of trigeminal nociceptors.

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