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Mauricio Sendeski - One of the best experts on this subject based on the ideXlab platform.
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noradrenaline enhances angiotensin ii responses via p38 mapk activation after hypoxia re oxygenation in renal Interlobar Arteries
Acta Physiologica, 2015Co-Authors: J Kaufmann, Mauricio Sendeski, Peter Martinka, O Moede, Andreas Steege, Michael Fahling, Michael Hultstrom, Matthias Gaestel, I C Moraessilva, Tatiana NikitinaAbstract:Aim Hypoxia and sympathetic activation are main factors in the pathogenesis of acute kidney injury (AKI). We tested the hypothesis that noradrenaline (NE) in combination with hypoxia aggravates the vasoreactivity of renal Arteries after hypoxia/re-oxygenation (H/R). We tested the role of adrenergic receptors and p38 MAPK using an in vitro H/R protocol. Methods Mouse Interlobar Arteries (ILA) and afferent arterioles (AA) were investigated under isometric and isotonic conditions respectively. The in vitro protocol consisted of 60-min hypoxia and control condition, respectively, 10-min re-oxygenation followed by concentration–response curves for Ang II or endothelin. Results Hypoxia reduced the response to Ang II. Hypoxia and NE (10−9 mol L-1) together increased it in ILA and AA. In ILA, NE alone influenced neither Ang II responses under control conditions nor endothelin responses after hypoxia. Prazosin or yohimbine treatment did not significantly influence the NE+hypoxia effect. The combination of prazosin and yohimbine or propranolol alone inhibited the effect of NE+hypoxia. BRL37344 (β3 receptor agonist) mimicked the NE effect. In contrast, the incubation with β3 receptor blocker did not influence the mentioned effect. Phosphorylation of p38 MAPK and MLC(20) was increased after H/R with NE and Ang II treatment. The selective p38 MAPK inhibitor SB202190 blocked the NE+hypoxia effect on the Ang II response. Conclusion The results suggest an interaction of NE and hypoxia in enhancing vasoreactivity, which may be important for the pathogenesis of AKI. The effect of NE+hypoxia in ILA is mediated by several adrenergic receptors and requires the p38 MAPK activation.
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angiotensin ii type 2 receptor mediates sex differences in mice renal Interlobar Arteries response to angiotensin ii
Journal of Hypertension, 2012Co-Authors: Vinicius U Viegas, Zhi Z Liu, Tatiana Nikitina, Andrea Perlewitz, Olga Zavaritskaya, Jeremias Schlichting, Pontus B Persson, Vera Regitzzagrosek, Andreas Patzak, Mauricio SendeskiAbstract:OBJECTIVE Functional sex differences are described in several vascular beds. In the case of renal vessels, sex differences could influence processes like regulation of blood pressure and ion balance. Angiotensin II and nitric oxide are important regulators of renal vascular tone. Females have higher nitric oxide synthase expression, nitric oxide bioavailability and ratio of angiotensin II type 2/type 1 receptors. Thus, our objective was to examine whether renal Interlobar Arteries present sex differences in their response to angiotensin II, and whether angiotensin II type 2 receptors play a role in such differences. METHODS We investigated the isometric contraction and relaxation of Interlobar Arteries from female and male mice under blockade of nitric oxide synthases and angiotensin II type 2 receptors. We also investigated the expression of angiotensin II receptors (type 1 and 2) and endothelial nitric oxide synthase. RESULTS Significantly less intense contraction to angiotensin II were seen in Arteries from females in comparison to male mice. Inhibition of nitric oxide synthases and endothelial removal abolished this difference. Angiotensin II type 2 receptors blockade enhanced contraction to angiotensin II in females, but not in males. Endothelial-dependent vasodilation was more dependent on nitric oxide in females than in males. Expression of angiotensin II type 1 and type 2 receptors was similar between sexes. Expression of endothelial nitric oxide synthase was higher in females. CONCLUSION A sex-specific, nitric oxide-mediated effect via angiotensin II type 2 receptors underlies the sex differences in the response of Interlobar Arteries to angiotensin II. Our findings may help understanding sex differences in renal hemodynamics and blood pressure control.
Tatiana Nikitina - One of the best experts on this subject based on the ideXlab platform.
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noradrenaline enhances angiotensin ii responses via p38 mapk activation after hypoxia re oxygenation in renal Interlobar Arteries
Acta Physiologica, 2015Co-Authors: J Kaufmann, Mauricio Sendeski, Peter Martinka, O Moede, Andreas Steege, Michael Fahling, Michael Hultstrom, Matthias Gaestel, I C Moraessilva, Tatiana NikitinaAbstract:Aim Hypoxia and sympathetic activation are main factors in the pathogenesis of acute kidney injury (AKI). We tested the hypothesis that noradrenaline (NE) in combination with hypoxia aggravates the vasoreactivity of renal Arteries after hypoxia/re-oxygenation (H/R). We tested the role of adrenergic receptors and p38 MAPK using an in vitro H/R protocol. Methods Mouse Interlobar Arteries (ILA) and afferent arterioles (AA) were investigated under isometric and isotonic conditions respectively. The in vitro protocol consisted of 60-min hypoxia and control condition, respectively, 10-min re-oxygenation followed by concentration–response curves for Ang II or endothelin. Results Hypoxia reduced the response to Ang II. Hypoxia and NE (10−9 mol L-1) together increased it in ILA and AA. In ILA, NE alone influenced neither Ang II responses under control conditions nor endothelin responses after hypoxia. Prazosin or yohimbine treatment did not significantly influence the NE+hypoxia effect. The combination of prazosin and yohimbine or propranolol alone inhibited the effect of NE+hypoxia. BRL37344 (β3 receptor agonist) mimicked the NE effect. In contrast, the incubation with β3 receptor blocker did not influence the mentioned effect. Phosphorylation of p38 MAPK and MLC(20) was increased after H/R with NE and Ang II treatment. The selective p38 MAPK inhibitor SB202190 blocked the NE+hypoxia effect on the Ang II response. Conclusion The results suggest an interaction of NE and hypoxia in enhancing vasoreactivity, which may be important for the pathogenesis of AKI. The effect of NE+hypoxia in ILA is mediated by several adrenergic receptors and requires the p38 MAPK activation.
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angiotensin ii type 2 receptor mediates sex differences in mice renal Interlobar Arteries response to angiotensin ii
Journal of Hypertension, 2012Co-Authors: Vinicius U Viegas, Zhi Z Liu, Tatiana Nikitina, Andrea Perlewitz, Olga Zavaritskaya, Jeremias Schlichting, Pontus B Persson, Vera Regitzzagrosek, Andreas Patzak, Mauricio SendeskiAbstract:OBJECTIVE Functional sex differences are described in several vascular beds. In the case of renal vessels, sex differences could influence processes like regulation of blood pressure and ion balance. Angiotensin II and nitric oxide are important regulators of renal vascular tone. Females have higher nitric oxide synthase expression, nitric oxide bioavailability and ratio of angiotensin II type 2/type 1 receptors. Thus, our objective was to examine whether renal Interlobar Arteries present sex differences in their response to angiotensin II, and whether angiotensin II type 2 receptors play a role in such differences. METHODS We investigated the isometric contraction and relaxation of Interlobar Arteries from female and male mice under blockade of nitric oxide synthases and angiotensin II type 2 receptors. We also investigated the expression of angiotensin II receptors (type 1 and 2) and endothelial nitric oxide synthase. RESULTS Significantly less intense contraction to angiotensin II were seen in Arteries from females in comparison to male mice. Inhibition of nitric oxide synthases and endothelial removal abolished this difference. Angiotensin II type 2 receptors blockade enhanced contraction to angiotensin II in females, but not in males. Endothelial-dependent vasodilation was more dependent on nitric oxide in females than in males. Expression of angiotensin II type 1 and type 2 receptors was similar between sexes. Expression of endothelial nitric oxide synthase was higher in females. CONCLUSION A sex-specific, nitric oxide-mediated effect via angiotensin II type 2 receptors underlies the sex differences in the response of Interlobar Arteries to angiotensin II. Our findings may help understanding sex differences in renal hemodynamics and blood pressure control.
Chao-yang Tan - One of the best experts on this subject based on the ideXlab platform.
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The Protective Effect of Propofol Against Ischemia-Reperfusion Injury in the Interlobar Arteries: Reduction of Abnormal Cx43 Expression as a Possible Mechanism.
Kidney & blood pressure research, 2018Co-Authors: Yue-chen Chang, Wen-jing Xue, Yang Wang, Yan‑ping Wang, Wen-yan Shi, Li-ya Shan, Liang Zhang, Chao-yang TanAbstract:BACKGROUND/AIMS This experimental study aims to observe whether the protective effect of propofol against renal ischemia-reperfusion injury (IRI) in the rat Interlobar artery occurs through altered expression of the gap junction protein connexin 43 (Cx43). METHODS This study randomly divided male Sprague Dawley (SD) rats into an untreated control group, a sham-operated control group (sham group), an ischemia-reperfusion group (IR group), a propofol group (propofol+IR group) and a fat emulsion group (Intralipid group). The ischemia/reperfusion model was prepared through resection of the right kidney and noninvasive arterial occlusion of the left kidney. Forty-five minutes after renal ischemia-reperfusion, an automatic biochemical analyzer was employed to measure blood urea nitrogen (BUN) and serum creatinine (SCr); changes in renal tissue pathology were observed using hematoxylin and eosin (HE) staining, and the vasomotor activity of the Interlobar artery was detected using a pressure mechanogram technique. The protein expression of Cx43 in renal artery cross-sections was determined through western blotting. RESULTS The experimental study confirmed that the BUN and SCr of rats markedly increased after ischemia-reperfusion injury; additionally, we observed some coagulation necrosis and shedding of cells, some solidification of nuclear chromatin, degeneration of cytoplasmic vacuoles, high renal interstitial vascular congestion and obvious inflammatory cell infiltration, characterized by focal hemorrhages. Furthermore, the contraction activity of the renal Interlobar artery greatly decreased, and the tension of the Arteries in the renal lobe increased remarkably. After the gap junction blocking agents 2-APB and Gap27 were applied, the systolic velocity of blood vessels and the vascular contraction rate both decreased. In addition, the expression of Cx43 in kidney tissues increased markedly. The damage was more severe after 24 h of ischemic reperfusion than after only 4 h. However, after pretreatment with propofol, regardless of whether ischemia-reperfusion was applied for 4 h or 24 h, the previously increased expression of Cx43 decreased obviously, and all forms of renal damage were reversed. CONCLUSION Our research suggests new ways for propofol to relieve ischemia-reperfusion injury by decreasing the abnormal expression of the gap junction protein Cx43. This study reveals a novel mechanism for the action of propofol against IRI, and we hope this finding will lead to new treatments for IRI.
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The Protective Effect of Propofol Against Ischemia–Reperfusion Injury in the Interlobar Arteries: Reduction of Abnormal Cx43 Expression as a Possible Mechanism
Karger Publishers, 2018Co-Authors: Yue-chen Chang, Wen-jing Xue, Yang Wang, Wen-yan Shi, Li-ya Shan, Liang Zhang, Yan-ping Wang, Chao-yang TanAbstract:Background/Aims: This experimental study aims to observe whether the protective effect of propofol against renal ischemia–reperfusion injury (IRI) in the rat Interlobar artery occurs through altered expression of the gap junction protein connexin 43 (Cx43). Methods: This study randomly divided male Sprague Dawley (SD) rats into an untreated control group, a sham-operated control group (sham group), an ischemia–reperfusion group (IR group), a propofol group (propofol+IR group) and a fat emulsion group (Intralipid group). The ischemia/reperfusion model was prepared through resection of the right kidney and noninvasive arterial occlusion of the left kidney. Forty-five minutes after renal ischemia–reperfusion, an automatic biochemical analyzer was employed to measure blood urea nitrogen (BUN) and serum creatinine (SCr); changes in renal tissue pathology were observed using hematoxylin and eosin (HE) staining, and the vasomotor activity of the Interlobar artery was detected using a pressure mechanogram technique. The protein expression of Cx43 in renal artery cross-sections was determined through western blotting. Results: The experimental study confirmed that the BUN and SCr of rats markedly increased after ischemia–reperfusion injury; additionally, we observed some coagulation necrosis and shedding of cells, some solidification of nuclear chromatin, degeneration of cytoplasmic vacuoles, high renal interstitial vascular congestion and obvious inflammatory cell infiltration, characterized by focal hemorrhages. Furthermore, the contraction activity of the renal Interlobar artery greatly decreased, and the tension of the Arteries in the renal lobe increased remarkably. After the gap junction blocking agents 2-APB and Gap27 were applied, the systolic velocity of blood vessels and the vascular contraction rate both decreased. In addition, the expression of Cx43 in kidney tissues increased markedly. The damage was more severe after 24 h of ischemic reperfusion than after only 4 h. However, after pretreatment with propofol, regardless of whether ischemia–reperfusion was applied for 4 h or 24 h, the previously increased expression of Cx43 decreased obviously, and all forms of renal damage were reversed. Conclusion: Our research suggests new ways for propofol to relieve ischemia–reperfusion injury by decreasing the abnormal expression of the gap junction protein Cx43. This study reveals a novel mechanism for the action of propofol against IRI, and we hope this finding will lead to new treatments for IRI
Michal L Schwartzman - One of the best experts on this subject based on the ideXlab platform.
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induction of angiotensin converting enzyme and activation of the renin angiotensin system contribute to 20 hydroxyeicosatetraenoic acid mediated endothelial dysfunction
Arteriosclerosis Thrombosis and Vascular Biology, 2012Co-Authors: Jennifer Cheng, John R Falck, Errabelli Ramu, Victor Garcia, Yan Ding, Krutanjali Thakar, Michal L SchwartzmanAbstract:Objective— 20-hydroxyeicosatetraenoic acid (20-HETE) promotes endothelial dysfunction by uncoupling endothelial NO synthase, stimulating O2− production, and reducing NO bioavailability. Moreover, 20-HETE–dependent vascular dysfunction and hypertension are associated with upregulation of the renin–angiotensin system This study was undertaken to examine the contribution of renin–angiotensin system to 20-HETE actions in the vascular endothelium. Methods and Results— In endothelial cells, 20-HETE induced angiotensin-converting enzyme (ACE) mRNA levels and increased ACE protein and activity by 2- to 3-fold; these effects were negated with addition of the 20-HETE antagonist, 20-hydroxyeicosa-6(Z),15(Z)-dienoic acid (20 HEDE). 20-HETE induced ACE expression was protein kinase C independent and epidermal growth factor receptor tyrosine kinase and IκB kinase β dependent. ACE short interfering RNA abolished 20-HETE–mediated inhibition of NO production and stimulation of O2− generation, whereas angiotensin II type 1 receptor short interfering RNA attenuated these effects by 40%. 20-HETE–stimulated O2− production was negated by 20-HEDE and was attenuated by lisinopril and losartan. Importantly, 20-HETE–mediated impairment of acetylcholine-induced relaxation in rat renal Interlobar Arteries was also attenuated by lisinopril and losartan. Conclusion— These results indicate that ACE and angiotensin II type 1 receptor activation contribute to 20-HETE–mediated endothelial cell and vascular dysfunction and further enforce the notion that excessive production of 20-HETE within the vasculature leads to hypertension via mechanisms that include the induction of endothelial ACE, thus, perpetuating an increase in vascular angiotensin which, together with 20-HETE, promotes vascular dysfunction.
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20-Hydroxy-5,8,11,14-eicosatetraenoic Acid Mediates Endothelial Dysfunction via IκB Kinase-Dependent Endothelial Nitric-Oxide Synthase Uncoupling
The Journal of pharmacology and experimental therapeutics, 2009Co-Authors: Jennifer Cheng, Katherine H. Gotlinger, Frank Zhang, Dubasi Narsimhaswamy, Michal L SchwartzmanAbstract:Endothelial dysfunction and activation occur in the vasculature and are believed to contribute to the pathogenesis of cardiovascular diseases. We have shown that 20-hydroxy-5,8,11,14-eicosatetraenoic acid (20-HETE), a cytochrome P450 4A-derived eicosanoid that promotes vasoconstriction in the microcirculation, uncouples endothelial nitric-oxide synthase (eNOS) and reduces nitric oxide (NO) levels via the dissociation of the 90-kDa heat shock protein (HSP90) from eNOS. It also causes endothelial activation by stimulating nuclear factor-κB (NF-κB) and increasing levels of pro-inflammatory cytokines. In this study, we examined signaling mechanisms that may link 20-HETE-induced endothelial dysfunction and activation. Under conditions in which 20-HETE inhibited NO production, it also stimulated inhibitor of NF-κB (IκB) phosphorylation. Both effects were prevented by inhibition of tyrosine kinases and mitogen-activated protein kinase (MAPK)/extracellular signal-regulated kinase (ERK). It is noteworthy that inhibitor of IκB kinase (IKK) activity negated the 20-HETE-mediated inhibition of NO production. Immunoprecipitation experiments revealed that treatment of ionophore-stimulated cells with 20-HETE brings about a decrease in HSP90-eNOS association and an increase in HSP90-IKKβ association, suggesting that the activation by 20-HETE of NF-κB is linked to its action on eNOS. Furthermore, addition of inhibitors of tyrosine kinase MAPK and IKK restored the 20-HETE-mediated impairment of acetylcholine-induced relaxation in rat renal Interlobar Arteries. The results indicate that 20-HETE mediates eNOS uncoupling and endothelial dysfunction via the activation of tyrosine kinase, MAPK, and IKK, and these effects are linked to 20-HETE-mediated endothelial activation.
Richard P E Van Dokkum - One of the best experts on this subject based on the ideXlab platform.
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vascular smooth muscle function of renal glomerular and Interlobar Arteries predicts renal damage in rats
American Journal of Physiology-renal Physiology, 2012Co-Authors: Peter Vavrinec, Robert H Henning, Maaike Goris, Diana Vavrincovayaghi, Hendrik Buikema, Richard P E Van DokkumAbstract:Previously, it was shown that individuals with good baseline (a priori) endothelial function in isolated (in vitro) renal Arteries developed less renal damage after ⅚ nephrectomy (5/6Nx; Gschwend S...