scholarly journals 0227 : Mineralocorticoid receptor deficiency in smooth muscle cells protects against renal injury induced by ischemia/reperfusion

2015 ◽  
Vol 7 (2) ◽  
pp. 151
Author(s):  
Jonatan Barrera-Chimal ◽  
Sonia Prince ◽  
Fouad Fadel ◽  
Alan Le Mercier ◽  
Soumaya El Moghrabi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Renal Injury ◽  
Mineralocorticoid Receptor ◽  
Ischemia Reperfusion ◽  
Muscle Cells

Abstract 133: Role of Vascular and Myeloid Mineralocorticoid Receptor in Renal Ischemia/reperfusion

Hypertension ◽  
2015 ◽  
Vol 66 (suppl_1) ◽  
Author(s):  
Jonatan Barrera-Chimal ◽  
Alan Le Mercier ◽  
Sonia Prince ◽  
Fouad Fadel ◽  
Soumaya El Moghrabi ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Renal Dysfunction ◽  
Mineralocorticoid Receptor ◽  
Ischemia Reperfusion ◽  
Muscle Cells ◽  
Cre Recombinase ◽  
Renal Ischemia ◽  
Plasma Creatinine ◽  
Mrna Levels

Introduction: Renal ischemia/reperfusion (IR) is a major cause of acute kidney injury. It is associated with cardiac alterations and chronic kidney disease (CKD) development. We previously showed that mineralocorticoid receptor (MR) antagonism prevents the acute and chronic consequences of renal IR (Barrera-Chimal, Kidney Int, 2013 and JASN, 2015). However, whether the benefit of the MR antagonists is due to the blockade of the MR expressed in the vessels is unclear. Objective: To study the specific contribution of endothelial and smooth muscle cells MR in acute and chronic consequences of renal IR. Methods: To evaluate the contribution of vascular MR we generated two knockout (KO) mouse models. To allow MR inactivation in endothelial cells (MR endoKO mice), floxed MR mice (MR fl/fl ) were crossed with mice expressing the inducible Cre recombinase under the VEcadh promoter. To allow MR inactivation in vascular smooth muscle cells (MR SMCKO mice), MR fl/fl mice were crossed with mice expressing the inducible Cre recombinase under the SMA promoter. In these mice, sham surgery or bilateral renal IR for 20 min was performed in MR fl/fl and KO mice and the animals were studied at short term (24 h) and long term (30 days) after reperfusion. Results: In MR fl/fl mice, IR induced renal dysfunction (plasma creatinine raised from 8.9±0.3 in sham to 33.8±4.8 umol/L in IR), tubular injury and increased mRNA levels of kim-1 (400-fold) and NGAL (220-fold). The MR endoKO mice displayed similar alterations induced by IR as MR fl/fl mice. In contrast, after 24 h of renal IR, the MR SMCKO mice presented normal renal function (plasma creatinine was 9.6±0.7 and 14.0±1.9 umol/L in sham and IR, respectively), absence of histological alterations and reduced kim-1 and NGAL levels. After 30 days, the MR fl/fl mice developed CKD characterized by renal dysfunction (plasma creatinine from 10.5±0.1in sham to 15±0.8 umol/L in IR), tubule-interstitial fibrosis and increased mRNA levels of fibronectin and Galectin-3 (2-fold). The MR SMCKO mice developed similar alterations. Conclusion: We provide evidence that the deficiency of MR in the SMC protects against the development of acute kidney lesions induced by IR, however MR deficiency in SMC did not impact the appearance of CKD induced by IR.

THE ROLE OF CALCIUM (CA2+) IN MODULATION OF SMOOTH MUSCLE CELLS REACTIVITY TO ANGIOTENSIN II (ANG II) DURING ISCHEMIA/REPERFUSION (I/R).

2008 ◽  
Vol 86 (Supplement) ◽  
pp. 736
Author(s):  
M Slupski ◽  
K Szadujkis-Szadurska ◽  
R Szadujkis-Szadurski ◽  
M Jasinski ◽  
G Grzesk
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Smooth Muscle Cells ◽  
Ischemia Reperfusion ◽  
Muscle Cells ◽  
Ang Ii

Peroxide resistance of ER Ca2+ pump in endothelium: implications to coronary artery function

1997 ◽  
Vol 273 (4) ◽  
pp. C1250-C1258 ◽  
Author(s):  
Ashok K. Grover ◽  
Sue E. Samson
Keyword(s):  
Endothelial Cells ◽  
Smooth Muscle ◽  
Coronary Artery ◽  
Smooth Muscle Cells ◽  
Cultured Cells ◽  
Contractile Function ◽  
Ischemia Reperfusion ◽  
Muscle Cells ◽  
Intact Cells ◽  
Serca Pump

We examined the effects of peroxide on the sarco(endo)plasmic reticulum Ca2+ (SERCA) pump in pig coronary artery endothelium and smooth muscle at three organizational levels: Ca2+ transport in permeabilized cells, cytosolic Ca2+ concentration in intact cells, and contractile function of artery rings. We monitored the ATP-dependent, azide-insensitive, oxalate-stimulated45Ca2+uptake by saponin-permeabilized cultured cells. Low concentrations of peroxide inhibited the uptake less effectively in endothelium than in smooth muscle whether we added the peroxide directly to the Ca2+ uptake solution or treated intact cells with peroxide and washed them before the permeabilization. An acylphosphate formation assay confirmed the greater resistance of the SERCA pump in endothelial cells than in smooth muscle cells. Pretreating smooth muscle cells with 300 μM peroxide inhibited (by 77 ± 2%) the cyclopiazonic acid (CPA)-induced increase in cytosolic Ca2+ concentration in a Ca2+-free solution, but it did not affect the endothelial cells. Peroxide pretreatment inhibited the CPA-induced contraction in deendothelialized arteries with a 50% inhibitory concentration of 97 ± 13 μM, but up to 500 μM peroxide did not affect the endothelium-dependent, CPA-induced relaxation. Similarly, 500 μM peroxide inhibited the angiotensin-induced contractions in deendothelialized arteries by 93 ± 2%, but it inhibited the bradykinin-induced, endothelium-dependent relaxation by only 40 ± 13%. The greater resistance of the endothelium to reactive oxygen may be important during ischemia-reperfusion or in the postinfection immune response.

scholarly journals Changes in guanylate cyclase activity in arteriolar smooth muscle cells and hemodynamics after ischemia-reperfusion in rats

1999 ◽  
Vol 98 (6) ◽  
pp. 603-613 ◽  
Author(s):  
H. Hashimoto ◽  
Shinsuke Ohta ◽  
Hiroshi Utsunomiya ◽  
Yoshiaki Kumon ◽  
Saburo Sakaki ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Guanylate Cyclase ◽  
Ischemia Reperfusion ◽  
Muscle Cells ◽  
Cyclase Activity ◽  
Guanylate Cyclase Activity

scholarly journals Ischemia-Reperfusion Does Not Affect Reactivity of Isolated Canine Basilar Artery

1991 ◽  
Vol 11 (5) ◽  
pp. 824-828 ◽  
Author(s):  
Zvonimir S. Katušić ◽  
John D. Michenfelder ◽  
James H. Milde
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Ischemia Reperfusion ◽  
Muscle Cells ◽  
Isometric Tension ◽  
Global Cerebral Ischemia ◽  
Physiological Salt Solution ◽  
Basilar Arteries

The effect of ischemia-reperfusion on endothelium-dependent relaxations and reactivity of vascular smooth-muscle cells was studied in rings of basilar arteries obtained from six dogs exposed to 12 min of complete global cerebral ischemia followed by 100 min of reperfusion. Three sham-operated control dogs served as controls. Ischemia was induced either by an increase in intracranial pressure or by aortic occlusion. The rings were suspended for isometric tension recording in physiological salt solution. Ischemia-reperfusion did not affect endothelium-dependent relaxations to vasopressin and bradykinin. In rings without endothelium relaxations to sodium nitroprusside, molsidomine (SIN-1), and papaverine as well as contractions to 5-hydroxytryptamine and KCl were preserved. These results demonstrate that in large canine cerebral arteries, ischemia-reperfusion of these durations does not affect relaxations mediated by activation of endothelium or direct relaxations and contractions of vascular smooth-muscle cells.

scholarly journals Mineralocorticoid Receptor in Calcium Handling of Vascular Smooth Muscle Cells

2018 ◽  
Author(s):  
Rogelio Salazar-Enciso ◽  
Nohemi A. Camacho-Concha ◽  
Thassio R. Mesquita ◽  
Débora Falcón ◽  
Jean-Pierre Benitah ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Mineralocorticoid Receptor ◽  
Muscle Cells ◽  
Calcium Handling

Delineating the receptor mechanisms underlying the rapid vascular contractile effects of aldosterone and estradiol

2011 ◽  
Vol 89 (9) ◽  
pp. 655-663 ◽  
Author(s):  
Robert Gros ◽  
Qingming Ding ◽  
Mark Davis ◽  
Rasha Shaikh ◽  
Bonan Liu ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Vascular Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Vascular Smooth Muscle Cells ◽  
Mineralocorticoid Receptor ◽  
Time Course ◽  
Cardiovascular Effects ◽  
Muscle Cells ◽  
Smooth Muscle Contraction ◽  
Cell Assays

It is increasingly appreciated that steroid hormones such as aldosterone and estradiol can mediate important cardiovascular effects. Many of these effects occur over a time course not consistent with the genomic actions of these hormones acting through classical nuclear receptors / transcription factors. Further, multiple receptors have been implicated in mediating these rapid effects of both aldosterone and estradiol, including a newly appreciated G-protein-coupled receptor, GPR30. In previous studies we demonstrated that both aldosterone and estradiol mediate contraction in vascular smooth muscle cells, as assessed in single cell assays. However, the receptor mechanisms underlying these effects remained unclear. Therefore, we studied the actions of estradiol and aldosterone on rat aortic vascular smooth muscle cells. Both aldosterone and estradiol mediated a concentration-dependent increase in contraction, as assessed in substrate deformation assays with EC50s in the range of nanomoles per litre. These effects paralleled increased myosin light chain phosphorylation. The effects of aldosterone were inhibited by the mineralocorticoid selective antagonist eplerenone. Further, aldosterone’s contractile effects were enhanced by increased expression of the mineralocorticoid receptor. The contractile effects of estradiol were inhibited by estrogen receptor (ER)-selective antagonists, tamoxifen, and ICI 182780, as well as eplerenone. Further, estradiol’s effects were enhanced by the increased expression of both ERα and the mineralocorticoid receptor (MR). To assess the potential role of GPR30 in mediating the effects of aldosterone and estradiol, GPR30 was re-introduced, since these cells lose endogenous GPR30 expression in culture. Re-expression of GPR30 enhanced both estradiol- and aldosterone-mediated contraction. These studies demonstrate that in rat aortic vascular smooth muscle cells, both aldosterone and estradiol mediate vascular smooth muscle contraction and that these effects can be mediated by MR, ERα, and by GPR30.

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