scholarly journals Renin-angiotensin system blockade: Effect on renal mRNA expression in 5/6 nephrectomized rats

Health ◽  
2013 ◽  
Vol 05 (04) ◽  
pp. 9-15 ◽  
Author(s):  
Erika Yadira Cruz-Laguna ◽  
Ana Ma. Gámez-Méndez ◽  
Hilda Vargas-Robles ◽  
Amelia Ríos ◽  
Alfonso Méndez-Tenorio ◽  
...  
Keyword(s):  
Mrna Expression ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin

Abstract 356: A Role for Renal Proximal Tubule Sodium Bicarbonate Cotransporter SLC4A5 in Salt-Sensitivity of Blood Pressure

Hypertension ◽  
2012 ◽  
Vol 60 (suppl_1) ◽  
Author(s):  
Julia M Carlson ◽  
John J Gildea ◽  
Helen E McGrath ◽  
Robin A Felder
Keyword(s):  
Sodium Bicarbonate ◽  
Proximal Tubule ◽  
Mrna Expression ◽  
Cell Lines ◽  
Renin Angiotensin System ◽  
Salt Sensitivity ◽  
Renal Proximal Tubule ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Homozygous Variant

SLC4A5 is a sodium-bicarbonate co-transporter involved with sodium homeostasis. Based on unpublished data, two SLC4A5 single nucleotide polymorphisms (SNPs rs1017783 and rs7571842) have been highly associated with an individual’s salt-sensitivity status. Since the renal proximal tubule (RPT) regulates a large percentage of renal sodium transport, we investigated whether SLC4A5 was present in this nephron segment. Using confocal immunofluorescence microscopy, we found expression of SLC4A5 in human RPT cell plasma membrane and intracellular membrane vesicles. We then examined the physiologic implications of the SLC4A5 SNPs in human RPT cells. Using immunoblotting and RT-PCR, we found no significant differences in basal SLC4A5 expression in RPT cells between individuals that are homozygous variant at both SNPs and individuals that are wild-type (WT) for both alleles. Stimulation of the dopaminergic system with 1μM fenoldopam, or the renin-angiotensin system with 10 nM angiotensin II or 10 nM angiotensin III (n=18 per treatment) over 3 and 24 hours did not significantly alter SLC4A5 protein or 24 hour mRNA expression. These data indicate that SLC4A5 is not directly regulated by either the renal dopaminergic or renin-angiotensin system. However, 24 hour stimulation with the sodium ionophore monensin (MON, 1μM) significantly increased overall mRNA expression of SLC4A5 by 182±0.098% over vehicle (VEH) (ΔCq VEH=0.283±0.035; n=18, p<0.001). There was also a significant increase in SLC4A5 mRNA in three cell lines homozygous variant for both alleles compared to three WT cell lines following MON treatment at both 3 hours (138±0.10%; ΔCq WT MON = 0.5±0.052; n=9, p<0.05) and 24 hours (161±0.11%; ΔCq WT MON = 0.39±0.066; n=9, p<0.02). Three but not 24 hour stimulation with MON also significantly increased overall expression of SLC4A5 protein (137±0.00041%; RFU VEH=0.0030±0.00022; n=18, p<0.01). MON, by allowing salt to enter a cell, may be activating an enhancer that leads to increased transcription of SLC4A5 mRNA that is more effective in homozygous variant cell lines. These novel observations demonstrate that SNPs located in a non-promoter DNA intron are associated with enhanced promoter activity that is regulated by altered intracellular sodium.

Renal Androgen and Renin Angiotensin System mRNA Expression in Polycystic Ovary Syndrome

2020 ◽  
Vol 34 (S1) ◽  
pp. 1-1
Author(s):  
Stephanie A. Ye ◽  
Steven Everman ◽  
Edgar D. Torres Fernandez ◽  
Damian G. Romero ◽  
Licy L. Yanes Cardozo
Keyword(s):  
Polycystic Ovary Syndrome ◽  
Mrna Expression ◽  
Polycystic Ovary ◽  
Renin Angiotensin System ◽  
Ovary Syndrome ◽  
Angiotensin System ◽  
Renin Angiotensin

Periaortic adipose tissue-specific activation of the renin-angiotensin system contributes to atherosclerosis development in uninephrectomized apoE−/− mice

2013 ◽  
Vol 305 (5) ◽  
pp. H667-H675 ◽  
Author(s):  
Hiroyuki Kawahito ◽  
Hiroyuki Yamada ◽  
Daisuke Irie ◽  
Taku Kato ◽  
Yoshiki Akakabe ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mrna Expression ◽  
Atherosclerotic Lesion ◽  
Renin Angiotensin System ◽  
Model Assessment ◽  
Ang Ii ◽  
Lesion Area ◽  
Perivascular Adipose Tissue ◽  
Angiotensin System ◽  
Renin Angiotensin

Chronic kidney disease (CKD) is an independent risk factor for the development of cardiovascular disease. The perivascular adipose tissue is closely implicated in the development of atherosclerosis; however, the contribution to CKD-associated atherogenesis remains undefined. Eight-week-old apoE-deficient mice were uninephrectomized and fed a high-cholesterol diet starting at 12 wk of age. The atherosclerotic lesion area in the thoracic aorta was comparable in 16-wk-old uninephrectomized (UNX) mice and sham control mice; however, the lesion area was markedly exaggerated in 20-wk-old UNX mice compared with the control (54%, P < 0.05). While the accumulation of monocytes/macrophages and the mRNA expression levels of inflammatory cytokines/chemokines in the thoracic periaortic adipose tissue (PAT) did not differ between the two groups, angiotensinogen (AGT) mRNA expression and the angiotensin II (ANG II) concentration in the PAT were significantly higher in 16-wk-old UNX mice than in the control (1.9- and 1.5-fold increases vs. control, respectively; P < 0.05). ANG II concentrations in both the plasma and epididymal white adipose tissue (WAT) were comparable between the two groups, suggesting that PAT-specific activation of the renin-angiotensin system (RAS) is primarily involved in CKD-associated atherogenesis. The homeostasis model assessment-insulin resistance (HOMA-IR) index and plasma insulin level after glucose loading were significantly elevated in 16-wk-old UNX mice. In vitro stimulation of preadipocytes with insulin exaggerated the AGT mRNA expression along with increased mRNA expression of PPARγ. These findings suggest that PAT-specific RAS activation probably primarily contributes in accelerating atherosclerotic development in UNX mice and could thus represent a therapeutic target for preventing CKD-associated atherogenesis.

scholarly journals The Uterine Placental Bed Renin-Angiotensin System in Normal and Preeclamptic Pregnancy

Endocrinology ◽  
2009 ◽  
Vol 150 (9) ◽  
pp. 4316-4325 ◽  
Author(s):  
Lauren Anton ◽  
David C. Merrill ◽  
Liomar A. A. Neves ◽  
Debra I. Diz ◽  
Jenny Corthorn ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Mrna Expression ◽  
Receptor Binding ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin Receptor ◽  
Angiotensin System ◽  
Chorionic Villi ◽  
Renin Angiotensin

Abstract Previously, we demonstrated activation of the renin-angiotensin system in the fetal placental chorionic villi, but it is unknown whether the immediately adjacent area of the maternal uterine placental bed is regulated similarly. This study measured angiotensin peptides, renin-angiotensin system component mRNAs, and receptor binding in the fundus from nonpregnant subjects (n = 19) and in the uterine placental bed from normal (n = 20) and preeclamptic (n = 14) subjects. In the uterine placental bed from normal pregnant women, angiotensin II peptide levels and angiotensinogen, angiotensin-converting enzyme, angiotensin receptor type 1 (AT1), AT2, and Mas mRNA expression were lower as compared with the nonpregnant subjects. In preeclamptic uterine placental bed, angiotensin II peptide levels and renin and angiotensin-converting enzyme mRNA expression were significantly higher than normal pregnant subjects. The AT2 receptor was the predominant receptor subtype in the nonpregnant fundus, whereas all angiotensin receptor binding was undetectable in normal and preeclamptic pregnant uterine placental bed compared with nonpregnant fundus. These findings suggest that the maternal uterine placental bed may play an endocrine role by producing angiotensin II, which acts in the adjacent placenta to vasoconstrict fetal chorionic villi vessels where we have shown previously that AT1 receptors predominate. This would lead to decreased maternal-fetal oxygen exchange and fetal nutrition, a known characteristic of preeclampsia.

Transcriptomic Response in the Heart and Kidney to Different Types of Antihypertensive Drug Administration

Hypertension ◽  
2021 ◽  
Author(s):  
Fumihiko Takeuchi ◽  
Yi-Qiang Liang ◽  
Masato Isono ◽  
Mia Yang Ang ◽  
Kotaro Mori ◽  
...  
Keyword(s):  
Body Weight ◽  
Mrna Expression ◽  
Antihypertensive Drug ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Heart Weight ◽  
Transcriptomic Response ◽  
Angiotensin System ◽  
Renin Angiotensin

Certain classes of antihypertensive drug may exert specific, blood pressure (BP)-independent protective effects on end-organ damages such as left ventricular hypertrophy, although the overall evidence has not been definitive in clinical trials. To unravel antihypertensive drug-induced gene expression changes that are potentially related to the amelioration of end-organ damages, we performed in vivo phenotypic evaluation and transcriptomic analysis on the heart and the kidney, with administration of antihypertensive drugs to two inbred strains (ie, hypertensive and normotensive) of rats. We chose 6 antihypertensive classes: enalapril (angiotensin-converting enzyme inhibitor), candesartan (angiotensin receptor blocker), hydrochlorothiazide (diuretics), amlodipine (calcium-channel blocker), carvedilol (vasodilating β-blocker), and hydralazine. In the tested rat strains, 4 of 6 drugs, including 2 renin-angiotensin system inhibitors, were effective for BP lowering, whereas the remaining 2 drugs were not. Besides BP lowering, there appeared to be some interdrug heterogeneity in phenotypic changes, such as suppressed body weight gain and body weight-adjusted heart weight reduction. For the transcriptomic response, a considerable number of genes showed prominent mRNA expression changes either in a BP-dependent or BP-independent manner with substantial diversity between the target organs. Noticeable changes of mRNA expression were induced particularly by renin-angiotensin system blockade, for example, for genes in the natriuretic peptide system ( Nppb and Corin ) in the heart and for those in the renin-angiotensin system/kallikrein-kinin system ( Ren and rat Klk1 paralogs) and those related to calcium ion binding ( Calb1 and Slc8a1 ) in the kidney. The research resources constructed here will help corroborate occasionally inconclusive evidence in clinical settings.

scholarly journals Renin-angiotensin system gene expression in the kidney and in the heart in hypertensive ISIAH rats

2011 ◽  
Vol 57 (4) ◽  
pp. 410-419 ◽  
Author(s):  
L.A. Fedoseeva ◽  
M.A. Ryazanova ◽  
E.V. Antonov ◽  
G.M. Dymshiz ◽  
A.L. Markel
Keyword(s):  
Arterial Hypertension ◽  
Mrna Expression ◽  
Renin Angiotensin System ◽  
Plasma Sodium ◽  
Isiah Rats ◽  
Ras Gene ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ras Genes ◽  
Hypertensive Isiah Rats

The content of mRNA of renin-angiotensin system (RAS) genes in the kidney and heart of hypertensive ISIAH and normotensive WAG rats was measured by the real-time PCR. Statistically significant decrease of RAS gene mRNA was registered in the kidney of ISIAH rats, including Ren (by 45%), Аce (43%), АТ1А (34%), СОХ-2 (50%). In the myocardium АТ1А mRNA expression decreased by 28% while Ace mRNA expression increased by 80%. These results demonstrate the reduction of renal RAS basal activity in the hypertensive ISIAH rats, and this allows us to consider the ISIAH rat, as a low-renin hypertensive strain.In support of this viewpoint, in the ISIAH rats, a two-fold increase in the connective tissue sodium concentration as well as statistically significant plasma sodium increase (from 136±0,25 μmol/l in WAG to 139±0,3 μmol/l in the ISIAH rats) were found. Our conclusion backed by a tendency of the ISIAH plasma aldosterone level decrease giving in sum a classical picture of a low-renin hypertensive state in the ISIAH rats.It was suggested that the formation of low-renin arterial hypertension in the ISIAH rats may depend on changes in kidney ion channels function. In addition, renal NO system alterations could be also involved in the pathogenesis of arterial hypertension in the ISIAH rats.

Role of endogenous renin-angiotensin system in c-fos activation and PKC-epsilon translocation in adult rat hearts

1996 ◽  
Vol 270 (6) ◽  
pp. H2177-H2183 ◽  
Author(s):  
P. M. Kang ◽  
A. Nakouzi ◽  
T. Simpson ◽  
J. Scheuer ◽  
P. M. Buttrick
Keyword(s):  
Protein Kinase C ◽  
Protein Kinase ◽  
Mrna Expression ◽  
Diastolic Pressure ◽  
Renin Angiotensin System ◽  
Left Ventricular ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Adult Rat ◽  
Kinase C

Myocardial stretch and the renin-angiotensin system have been implicated in the development of cardiac hypertrophy through the activation of specific target genes. However, the relative importance of these putative hypertrophic stimuli has not been established in vivo. We used an isolated isovolumic heart preparation in which coronary perfusion pressure (CPP), left ventricular end-diastolic pressure, and pharmacological therapy can be independently manipulated to study this relationship. High CPP (140 cmH2O), which increased coronary flow (8.99 vs. 17.6 ml/min) and left ventricular systolic pressure (50 vs. 91 mmHg), increased steady state c-fos mRNA expression 2.3-fold (all P < 0.01 vs. low CPP). In contrast, increased left ventricular end-diastolic pressure (25 mmHg) and/or infusion of angiotensin II in the absence of increased CPP was not associated with an increase in c-fos mRNA expression. The change in c-fos gene expression seen with increased CPP was largely reversed by treatment with an angiotensin type 1 (AT1) receptor blocker. Hearts perfused at high CPP demonstrated increased translocation/activation of protein kinase C-epsilon relative to controls. None of the hearts studied were ischemic during perfusion. Thus, in the perfused adult rat heart, dynamic, but not static, stretch activates the early response gene, c-fos, and may involve the endogenous reninangiotensin system and protein kinase C.

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