Effect of vasoactive agents on induction of Egr-1 in rat mesangial cells: correlation with mitogenicity

1992 ◽  
Vol 263 (4) ◽  
pp. F623-F636 ◽  
Author(s):  
H. D. Rupprecht ◽  
P. Dann ◽  
V. P. Sukhatme ◽  
R. B. Sterzel ◽  
D. L. Coleman
Keyword(s):  
Mesangial Cells ◽  
Close Correlation ◽  
Early Response ◽  
Mrna Levels ◽  
Ang Ii ◽  
Vasoactive Agents ◽  
Induction Process ◽  
Early Growth Response Gene ◽  
The Family

The early growth response gene 1 (Egr-1) is a member of the family of immediate early response genes. Egr-1 encodes a nuclear phosphoprotein that binds a specific nonameric DNA sequence through three zinc-finger domains and functions as a transcriptional activator. We tested whether the vasoactive agents platelet-derived growth factor (PDGF), arginine vasopressin (AVP), serotonin (5-HT), and angiotensin II (ANG II) induced Egr-1 mRNA in cultured rat mesangial cells (MCs) and investigated the role of protein kinase C (PKC) in mediating the induction process. PDGF, AVP, and 5-HT induced Egr-1 mRNA within 15 min, reaching peak levels at 45-60 min. After PDGF and 5-HT stimulation, Egr-1 mRNA levels returned to baseline within 4 h, whereas AVP induced a sustained increase for up to 8 h. There was a very close correlation between doses required for Egr-1 induction and induction of MC proliferation. ANG II was a very weak MC mitogen and induced only a small increase in Egr-1 mRNA. Comparison of control cells with cells depleted of PKC by 48 h of PMA treatment revealed that induction of Egr-1 by PDGF and 5-HT is independent of PKC. In contrast, however, the Egr-1 response to AVP was diminished in PKC-depleted cells. AVP induced Egr-1 mRNA 10.9-fold in control cells, compared with 7.8-fold in PKC-depleted cells. Egr-1 mRNA after AVP stimulation remained elevated in control cells for up to 8 h but returned to baseline after 120 min in PKC-depleted cells. Similar results were obtained using the PKC-inhibitor H-7. Using immunocytochemistry, PDGF and AVP were found to induce Egr-1 protein within 30 min localized to the nucleus. We conclude that there is a strong correlation between induction of Egr-1 after stimulation with PDGF, AVP, 5-HT, and ANG II and the proliferative response elicited by these agents in MCs. AVP induces Egr-1 by both PKC-dependent and PKC-independent pathways, whereas the effects of PDGF and 5-HT are independent of PKC.

Role of endothelium-derived relaxing factors in the renal response to vasoactive agents in hypothyroid rats

2003 ◽  
Vol 285 (1) ◽  
pp. E182-E188 ◽  
Author(s):  
Juan Manuel Moreno ◽  
Rosemary Wangensteen ◽  
Juan Sainz ◽  
Isabel Rodríguez-Gomez ◽  
Virginia Chamorro ◽  
...  
Keyword(s):  
Vascular Reactivity ◽  
Ang Ii ◽  
Vasoactive Agents ◽  
Normal Response ◽  
No Donor ◽  
Increased Sensitivity ◽  
Renal Vascular ◽  
And Control ◽  
Renal Responses

This study analyzed the role of nitric oxide (NO) and endothelium-derived hyperpolarizing factor (EDHF) in the abnormal renal vascular reactivity of hypothyroid rats. Renal responses to vasoconstrictors [VC: phenylephrine (PHE) and ANG II] and vasodilators [VD: ACh, sodium nitroprusside (SNP), and papaverine (PV)] were studied in kidneys from control and hypothyroid rats under normal conditions and after NO or EDHF blockade. NO was blocked by the administration of Nω-nitro-l-arginine methyl ester (l-NAME) and EDHF by the administration of tetraethylammonium (TEA) or by an increased extracellular K+. The response to VC was also evaluated after endothelium removal. Hypothyroid kidneys showed reduced responsiveness to PHE and a normal response to ANG II. l-NAME and TEA administration produced an increased sensitivity to PHE and to ANG II in control preparations. l-NAME also increased the response to PHE in hypothyroid kidneys, but the differences between control and hypothyroid kidneys were maintained. TEA administration did not change the response to either VC in hypothyroid preparations. In endothelium-removed preparations, TEA was unable to increase pressor responsiveness to VC. Hypothyroid kidneys showed reduced responsiveness to ACh and SNP and normal response to PV. The differences between hypothyroid and control preparations in the responses to ACh and SNP were maintained after l-NAME or increased K+. In conclusion, this study shows that 1) the attenuated response to PHE in hypothyroidism is not related to an increased production of endothelium-derived relaxing factors NO and EDHF; 2) the response to VC in hypothyroid preparations is insensitive to EDHF blockade; and 3) hypothyroid preparations have a reduced reactivity to the NO donor, and NO-independent vasodilatation remains unaffected.

Cardiac chymase: pathophysiological role and therapeutic potential of chymase inhibitors

2005 ◽  
Vol 83 (2) ◽  
pp. 123-130 ◽  
Author(s):  
Sheila A Doggrell ◽  
Janet C Wanstall
Keyword(s):  
Myocardial Infarction ◽  
Mast Cells ◽  
Animal Models ◽  
Therapeutic Potential ◽  
Pressure Overload ◽  
Mrna Levels ◽  
Ang Ii ◽  
Pathophysiological Role ◽  
Orally Active

On release from cardiac mast cells, α-chymase converts angiotensin I (Ang I) to Ang II. In addition to Ang II formation, α-chymase is capable of activating TGF-β1 and IL-1β, forming endothelins consisting of 31 amino acids, degrading endothelin-1, altering lipid metabolism, and degrading the extracellular matrix. Under physiological conditions the role of chymase in the mast cells of the heart is uncertain. In pathological situations, chymase may be secreted and have important effects on the heart. Thus, in animal models of cardiomyopathy, pressure overload, and myocardial infarction, there are increases in both chymase mRNA levels and chymase activity in the heart. In human diseased heart homogenates, alterations in chymase activity have also been reported. These findings have raised the possibility that inhibition of chymase may have a role in the therapy of cardiac disease. The selective chymase inhibitors developed to date include TY-51076, SUN-C8257, BCEAB, NK320, and TEI-E548. These have yet to be tested in humans, but promising results have been obtained in animal models of myocardial infarction, cardiomyopathy, and tachycardia-induced heart failure. It seems likely that orally active inhibitors of chymase could have a place in the treatment of cardiac diseases where injury-induced mast cell degranulation contributes to the pathology.Key words: cardiac chymase, pathophysiological role, inhibition.

Effects of vasoactive agents on uptake of immunoglobulin G complexes by mesangial cells

1990 ◽  
Vol 258 (3) ◽  
pp. F589-F596
Author(s):  
P. C. Singhal ◽  
A. Santiago ◽  
J. Satriano ◽  
R. M. Hays ◽  
D. Schlondorff
Keyword(s):  
Immunoglobulin G ◽  
Cytochalasin B ◽  
Mesangial Cells ◽  
Ang Ii ◽  
Hemodynamic Effects ◽  
Vasoactive Agents ◽  
Camp Content ◽  
Gold Particles ◽  
Cyclic Monophosphate ◽  
Immune Injury

Mesangial handling of immune complexes may be important in immune injury. We examined whether vasoactive agents, independent of hemodynamic effects, could directly influence uptake of immunoglobulin G (IgG) complexes by mesangial cells (MC). Under basal conditions, MC took up more gold particles coated with IgG2b (P less than 0.05) than coated with IgG2a. Preincubation of MC with angiotensin II (ANG II) (5 x 10(-7) M) resulted in enhancement of uptake (P less than 0.05) of IgG2b-gold [7,578 +/- 968 counts per minute (cpm) per well], IgG2a-gold (4,566 +/- 295 cpm/well; P less than 0.01), and bovine serum albumin (BSA)-gold (2,532 +/- 66; P less than 0.05) when compared with respective controls (IgG2b-gold, 5,513 +/- 762 cpm/well; IgG2a-gold, 3,282 +/- 439; BSA-gold, 2,279 +/- 97). Cytochalasin B produced a significant reduction of uptake of IgG2b-gold (2,224 +/- 88 cpm/well) when compared with the uptake by control cells (3,711 +/- 287 cpm/well) (P less than 0.05). Pretreatment of MC with atrial natriuretic peptide (ANP, 10(-9) M) slightly decreased uptake of IgG-gold under basal conditions (P less than 0.05) and decreased the response to ANG II (P less than 0.05). Similarly, dopamine (DA, 10(-6) M) attenuated uptake of IgG2b-gold under basal (P less than 0.01) as well as ANG II-stimulated (P less than 0.01) states. ANP increased mesangial guanosine 3',5'-cyclic monophosphate (cGMP), DA, adenosine 3',5'-cyclic monophosphate (cAMP) content.(ABSTRACT TRUNCATED AT 250 WORDS)

Regulation of liver angiotensinogen and kidney renin mRNA levels by angiotensin II

1990 ◽  
Vol 258 (1) ◽  
pp. E1-E6 ◽  
Author(s):  
A. Nakamura ◽  
H. Iwao ◽  
K. Fukui ◽  
S. Kimura ◽  
T. Tamaki ◽  
...  
Keyword(s):  
Blot Hybridization ◽  
Mrna Level ◽  
Control Level ◽  
Renin Angiotensin System ◽  
Northern Blot Hybridization ◽  
Mrna Levels ◽  
Ang Ii ◽  
Low Sodium ◽  
Renin Mrna

The current study was designed to evaluate the role of angiotesin II (ANG II) in the regulation of renin mRNA and angiotensinogen mRNA levels. We investigated the changes in renin mRNA levels in the kidney and angiotensinogen mRNA levels in the liver induced by ANG II infusion and by inhibition of the endogenous renin-angiotensin system with enalapril or saralasin in rats. mRNAs for angiotensinogen and renin were measured by densitometric analysis of Northern blot hybridization. After a 4-h intravenous infusion of ANG II (0.2 micrograms.kg-1.min-1), angiotensinogen mRNA level in the liver increased 2.5-fold to the control level, and renin mRNA level in the kidney decreased by 45%. Four hours after treatment with a single dose of enalapril (3 mg/kg po), angiotensinogen mRNA level in the liver decreased by 50%, and renin mRNA level in the kidney increased 1.5-fold to the control level. These mRNA levels returned to control levels 8 h after treatment. After a 4-h infusion of saralasin (2.5 micrograms.kg-1.min-1) in the low-sodium state, angiotensinogen mRNA level in the liver decreased by 45%, and renin mRNA level in the kidney increased twofold to the control level. These findings suggest that ANG II is one of the factors that regulate angiotensinogen mRNA level in the liver and renin mRNA level in the kidney.

Role of AT1 and AT2 receptors in regulation of MAPKs and MKP-1 by ANG II in adult cardiac myocytes

1998 ◽  
Vol 275 (3) ◽  
pp. H906-H916 ◽  
Author(s):  
Thomas A. Fischer ◽  
Krishna Singh ◽  
Donald S. O’Hara ◽  
David M. Kaye ◽  
Ralph A. Kelly
Keyword(s):  
Endothelial Cells ◽  
Protein Kinase ◽  
Protein Kinases ◽  
Ventricular Myocytes ◽  
Mrna Levels ◽  
Ang Ii ◽  
Terminal Protein ◽  
Erk Activity ◽  
Angiotensin Type

ANG II has been implicated in the hypertrophic response in ventricular myocytes by acting at the angiotensin type 1 (AT1) receptor. However, the role of the angiotensin type 2 (AT2) receptor in the adult heart is not as clearly understood. In adult rat ventricular myocytes (ARVM) and cardiac microvascular endothelial cells (CMEC), we examined the role of ANG II signaling, via AT1 and AT2 receptors, on the activation of the extracellular signal-regulated protein kinases (ERKs) and on the expression of the mitogen-activated protein kinase (MAPK) phosphatase MKP-1. ANG II caused no detectable increase in ERK activity or in c- fos mRNA abundance in ARVM but increased ERK activity within 5 min in CMEC and increased c- fos mRNA levels. However, in the presence of the selective phosphoprotein phosphatase (PP-2A/PP-1) inhibitor okadaic acid (OA), a sustained increase in ERK activity, as well as in c- junNH2-terminal protein kinase activity, in ARVM was observed. ANG II increased MKP-1 mRNA levels within 15 min in ARVM and CMEC. In contrast to the response in endothelial cells, however, ANG II activation of MKP-1 in ARVM was mediated by AT2-receptor activation. Thus there is constitutive as well as inducible suppression of ERKs and c- junNH2-terminal protein kinases by MKP and PP-2A/PP-1 in the adult cardiac myocyte phenotype.

Characterization of angiotensin IV-degrading enzymes and receptors on rat mesangial cells

1998 ◽  
Vol 275 (4) ◽  
pp. F535-F542 ◽  
Author(s):  
Dominique Chansel ◽  
Stanislas Czekalski ◽  
Sophie Vandermeersch ◽  
Emmanuel Ruffet ◽  
Marie-Claude Fournié-Zaluski ◽  
...  
Keyword(s):  
Mesangial Cells ◽  
Biological Effects ◽  
Neutral Endopeptidase ◽  
Cytosolic Calcium ◽  
Ang Ii ◽  
Degrading Enzymes ◽  
Specific Receptors ◽  
Ang Iv

Because mesangial cells (MC) are a target and a degradation site for angiotensin II (ANG II), we characterized the degrading enzymes and receptors of ANG IV, a metabolite of ANG II, on these cells. ANG IV was metabolized into its NH2-terminal deleted peptides, ANG II-(4–8), ANG II-(5–8), and ANG II-(6–8) by rat MC. Total protection of ANG IV was obtained only when PC-18, a specific aminopeptidase N (APN) inhibitor, and JFH-27A, a mixed inhibitor of dipeptidylaminopeptidase (DAP) and neutral endopeptidase (NEP), were simultaneously added. In contrast, thiorphan, an NEP inhibitor, was inactive. These results demonstrate the exclusive role of APN and DAP in ANG IV degradation.125I-labeled ANG IV binding was studied in the presence of PC-18 and JFH-27A to suppress ligand degradation. Under these conditions, ANG IV-specific receptors could be demonstrated with a K D of 1.8 nM and a density of 55 fmol/mg. In contrast with MC, no evidence for ANG IV receptors could be obtained in freshly isolated glomeruli. ANG IV stimulated cytosolic calcium concentration in MC, whereas its NH2-terminal deleted metabolites were inactive. Therefore, ANG IV must be protected from degradation by APN and DAP in studies on the nonimmediate biological effects of this peptide.

scholarly journals Characteristics of Protooncogene Expression in A5 Cells

1993 ◽  
Vol 4 (3) ◽  
pp. 531-535
Author(s):  
Eleni Kousvelari ◽  
Chih-Ko Yeh
Keyword(s):  
Cell Cycle ◽  
Adrenergic Receptors ◽  
Early Response ◽  
Mrna Levels ◽  
Intracellular Pathways ◽  
Early Response Genes ◽  
Β Adrenergic Receptors ◽  
Jun B ◽  
Stimulation Of

Stimulation of β-adrenergic receptors by isoproterenol or addition of 8-BrcAMP rapidly and transiently induces the expression of the protooncogenes, c-fos, and jun B, but not that of c-jun in A5 cells. These results indicate that different intracellular pathways may operate within the same cell for the induction of this group of early response genes. The inducibility of c-fos and jun B genes by either isoproterenol of 8-BrcAMP is transcriptionally regulated and accompanied by increases in their respective products. Furthermore, both c-fos and jun B mRNA levels are elevated at G0/G 1 phase of the A5 cell cycle and are inducible by isoproterenol or 8-BrcAMP at the different phases of the cell cycle. These data further suggest a possible role of c-fos and jun B in A5 cell cycle.

Differential regulation of angiotensin II and losartan binding sites in glomeruli and mesangial cells

1994 ◽  
Vol 266 (3) ◽  
pp. F384-F393 ◽  
Author(s):  
D. Chansel ◽  
T. Bizet ◽  
S. Vandermeersch ◽  
P. Pham ◽  
B. Levy ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Binding Sites ◽  
Mesangial Cells ◽  
Present Report ◽  
Mrna Levels ◽  
Ang Ii ◽  
Experimental Conditions ◽  
Human Mesangial Cells

The aim of the present report was to examine the effect of several agents on angiotensin II (ANG II) and losartan receptors using 125I-[Sar1,Ala8]ANG II and [3H]losartan as radiolabeled ligand, respectively. ANG II receptors were downregulated in glomeruli from rats infused with ANG II during 3 wk or rats receiving losartan orally during 1 wk. The number of sites (Bmax) was reduced, but the dissociation constant (Kd) value was unchanged. Losartan receptors were downregulated in glomeruli from rats receiving losartan, but remained unchanged in glomeruli from rats infused with ANG II. Since in vivo administration of losartan results in increase of plasma ANG II and formation of metabolites, in vitro studies using human mesangial cells were performed to better analyze the present findings. Treatment of mesangial cells during 4 days by ANG II, losartan, or its metabolite, EXP-3174, also produced downregulation of 125I-[Sar1,Ala8]ANG II binding sites with a decreased Bmax and unchanged Kd value. Only treatment of mesangial cells by ANG II or EXP-3174 produced downregulation of [3H]losartan binding sites. In contrast, exposure of these cells to losartan resulted in upregulation of [3H]losartan binding sites. Under all conditions, only Bmax was modified. Whereas internalization of [3H]losartan in mesangial cells was negligible under all experimental conditions, there was an increase of the percentage of internalized 125I-[Sar1,Ala8]ANG II after exposure of the cells to ANG II or AT1 antagonists. No change was observed in mesangial cell AT1 receptor mRNA levels. This study demonstrates that 1) AT1 mRNA is expressed in human mesangial cells; 2) the characteristics of 125I-[Sar1,Ala8]ANG II and [3H]losartan binding sites in rat glomeruli and human mesangial cells are different, with Kd and Bmax values greater in both preparations when [3H]losartan was utilized; 3) both types of binding sites obey different regulations, and the effects of losartan in vivo are due in part to the associated increase in plasma ANG II levels and the transformation of the drug into its metabolite, EXP-3174; 4) downregulation of AT1 receptors does not depend on changes in mRNA expression but is associated with increased relative internalization.

scholarly journals Identification and function of adenosine A3 receptor in afferent arterioles

2015 ◽  
Vol 308 (9) ◽  
pp. F1020-F1025 ◽  
Author(s):  
Yan Lu ◽  
Rui Zhang ◽  
Ying Ge ◽  
Mattias Carlstrom ◽  
Shaohui Wang ◽  
...  
Keyword(s):  
Receptor Agonist ◽  
Receptor Activation ◽  
Mrna Levels ◽  
Afferent Arteriole ◽  
Ang Ii ◽  
Adenosine A3 Receptor ◽  
Afferent Arterioles ◽  
And Function ◽  
Dilatory Effect

Adenosine plays an important role in regulation of renal microcirculation. All receptors of adenosine, A1, A2A, A2B, and A3, have been found in the kidney. However, little is known about the location and function of the A3 receptor in the kidney. The present study determined the expression and role of A3 receptors in mediating the afferent arteriole (Af-Art) response and studied the interaction of A3 receptors with angiotensin II (ANG II), A1 and A2 receptors on the Af-Art. We found that the A3 receptor expressed in microdissected isolated Af-Art and the mRNA levels of A3 receptor were 59% of A1. In the isolated microperfused Af-Art, A3 receptor agonist IB-MECA did not have a constrictive effect. Activation of A3 receptor dilated the preconstricted Af-Art by norepinephrine and blunted the vasoconstrictive effect of both adenosine A1 receptor activation and ANG II on the Af-Art, respectively. Selective A2 receptor antagonist (both A2A and A2B) had no effect on A3 receptor agonist-induced vasodilation, indicating that the dilatory effect of A3 receptor activation is not mediated by activation of A2 receptor. We conclude that the A3 receptor is expressed in the Af-Art, and activation of the A3 receptor dilates the Af-Art.

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