Effects of angiotensin II receptor blockade versus angiotensin-converting-enzyme inhibition on ventricular remodelling following myocardial infarction in the mouse

2003 ◽  
Vol 104 (2) ◽  
pp. 109-118 ◽  
Author(s):  
Richard D. PATTEN ◽  
Mark J. ARONOVITZ ◽  
Michael EINSTEIN ◽  
Matthew LAMBERT ◽  
Natesa G. PANDIAN ◽  
...  
Keyword(s):  
Gene Expression ◽  
Collagen Type ◽  
Receptor Gene ◽  
Ace Inhibition ◽  
At1 Receptor ◽  
Ang Ii ◽  
At1a Receptor ◽  
Collagen Type 1 ◽  
Receptor Gene Expression

Left ventricular (LV) remodelling following myocardial infarction (MI) is associated with increased morbidity and mortality. Previous data suggest that angiotensin II (Ang II) plays a central role in the molecular events contributing to LV remodelling. We explored the effects of angiotensin-converting-enzyme (ACE) inhibition versus Ang II (AT1) receptor blockade on LV remodelling in mice post-MI. Mice underwent sham procedure or left coronary artery ligation, and received placebo, the AT1 receptor antagonist, losartan or the ACE inhibitor, enalapril. At 6 weeks, echocardiography and haemodynamic studies were performed. Infarct size and interstitial collagen content were determined. Expression of genes encoding atrial natriuretic peptide (ANP), collagen type I, AT1a and AT1b receptors were measured. The placebo MI group showed increased LV end-diastolic diameter, LV end-systolic diameter with depressed fractional shortening (P<0.01 versus shams), increased LV mass and volume (both P<0.01 versus shams). The placebo MI group also exhibited increased non-infarct zone collagen content (P<0.01), ANP (P<0.01) and collagen type 1 (P<0.01) gene expression, with a non-significant rise in AT1a receptor gene expression. Neither losartan or enalapril prevented LV dilation or improved fractional shortening. Both similarly lowered systolic blood pressure (P<0.01 for each versus placebo). Losartan and enalapril inhibited LV hypertrophy (P<0.01), and decreased ANP (P<0.01) and collagen type 1 gene expression (P<0.05). Levels of AT1a receptor gene expression were higher than shams (P<0.05 for both), but similar to placebo. AT1b receptor gene expression was much lower than that for AT1a receptor and similar in all groups. Thus, in this model, AT1 receptor antagonism and ACE inhibition have equivalent inhibitory effects on myocardial hypertrophy and fibrosis. These results serve as an important basis for planned investigations to evaluate the anti-remodelling effects of these agents on mice in which genetic manipulations are used to disrupt components of the Ang II signalling system.

Decreased perfusion pressure modulates renin and ANG II type 1 receptor gene expression in the rat kidney

1993 ◽  
Vol 264 (4) ◽  
pp. R696-R702 ◽  
Author(s):  
A. Tufro-McReddie ◽  
R. L. Chevalier ◽  
A. D. Everett ◽  
R. A. Gomez
Keyword(s):  
Gene Expression ◽  
Aortic Coarctation ◽  
Perfusion Pressure ◽  
Receptor Gene ◽  
At1 Receptor ◽  
Northern Analysis ◽  
Renin Gene ◽  
Renin Mrna ◽  
Receptor Gene Expression

To determine whether decreased perfusion pressure affects the abundance and distribution of renin and its mRNA and the expression of the angiotensin II type 1 (AT1) receptor gene within the kidney, adult male Sprague-Dawley rats were subjected to aortic coarctation proximal to the renal arteries (Coarc, n = 8) and compared with sham-operated rats (Sham, n = 6). Renal renin distribution was determined by immunocytochemistry using a specific polyclonal antibody against rat renin. Renin mRNA was assessed by in situ hybridization to a 35S-labeled oligonucleotide complementary to rat renin mRNA. Kidney AT1 mRNA levels were determined by Northern analysis using a 1,133-base pair rat AT1 cDNA. Femoral arterial blood pressure, measured 24 h after surgery, was lower in Coarc than in Sham rats (75 +/- 5.4 vs. 122 +/- 2.3 mmHg, P < 0.05). Aortic coarctation increased the percent of juxtaglomerular apparatuses (%JGA) containing renin and its mRNA (85 +/- 2.5 and 66 +/- 2.8 vs. 49 +/- 5.3 and 36 +/- 1.7%, Coarc vs. Sham, P < 0.05) and the intensity of hybridization signals (497 +/- 89 vs. 71 +/- 12 grains/JGA, Coarc vs. Sham, P < 0.05). In addition, recruitment of renin gene expressing cells was observed along afferent arterioles in Coarc rats, whereas renin and its mRNA were limited to the JGAs in Sham rats. Renal AT1 receptor gene expression was threefold lower in Coarc than in Sham rats. We conclude that reduction of perfusion pressure after abdominal aortic coarctation acutely enhances renin gene expression and downregulates AT1 receptor gene expression.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin type-1 (AT1) receptor gene expression in primarily cultured human arterial umbilical endothelial cells

1997 ◽  
Vol 53 (3) ◽  
pp. 417-421 ◽  
Author(s):  
Yon Ko ◽  
Bernhard Glodny ◽  
Sebastian Stier ◽  
Gudrun Totzke ◽  
Georg Nickenig ◽  
...  
Keyword(s):  
Gene Expression ◽  
Endothelial Cells ◽  
Receptor Gene ◽  
At1 Receptor ◽  
Receptor Gene Expression ◽  
Angiotensin Type

scholarly journals Direct comparison of 3D and 2D cultivation reveals higher osteogenic capacity of elderly osteoblasts in 3D

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Stephan Payr ◽  
Elizabeth Rosado-Balmayor ◽  
Thomas Tiefenboeck ◽  
Tim Schuseil ◽  
Marina Unger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Collagen Type ◽  
3D Culture ◽  
Osteogenic Potential ◽  
Donor Age ◽  
Collagen Type 1 ◽  
2D And 3D ◽  
Human Primary Osteoblasts ◽  
Gene Expression Levels

Abstract Background The aim of this study was the investigation of the osteogenic potential of human osteoblasts of advanced donor age in 2D and 3D culture. Methods Osteoblasts were induced to osteogenic differentiation and cultivated, using the same polystyrene material in 2D and 3D culture for 2 weeks. Samples were taken to evaluate alkaline phosphatase (ALP) activity, mineralization and gene expression. Results Osteoprotegerin (OPG) levels were significantly increased (8.2-fold) on day 7 in 3D compared to day 0 (p < 0.0001) and 11.6-fold higher in 3D than in 2D (p < 0.0001). Both culture systems showed reduced osteocalcin (OC) levels (2D 85% and 3D 50% of basic value). Collagen type 1 (Col1) expression was elevated in 3D on day 7 (1.4-fold; p = 0.009). Osteopontin (OP) expression showed 6.5-fold higher levels on day 7 (p = 0.002) in 3D than in 2D. Mineralization was significantly higher in 3D on day 14 (p = 0.0002). Conclusion Advanced donor age human primary osteoblasts reveal significantly higher gene expression levels of OPG, Col1 and OP in 3D than in monolayer. Therefore, it seems that a relatively high potential of bone formation in a natural 3D arrangement is presumably still present in osteoblasts of elderly people. Trial registration 5217/11 on the 22nd of Dec. 2011.

scholarly journals Intrapulmonary Activation of the Angiotensin-Converting Enzyme Type 2/Angiotensin 1-7/G-Protein-Coupled Mas Receptor Axis Attenuates Pulmonary Hypertension in Ren-2 Transgenic Rats Exposed to Chronic Hypoxia

2015 ◽  
pp. 25-38 ◽  
Author(s):  
V. HAMPL ◽  
J. HERGET ◽  
J. BÍBOVÁ ◽  
A. BAŇASOVÁ ◽  
Z. HUSKOVÁ ◽  
...  
Keyword(s):  
Gene Expression ◽  
Pulmonary Hypertension ◽  
Receptor Gene ◽  
Ang Ii ◽  
Transgenic Rats ◽  
Hypoxic Pulmonary Hypertension ◽  
Mas Receptor ◽  
Receptor Gene Expression ◽  
Expression And Activity

The present study was performed to evaluate the role of intrapulmonary activity of the two axes of the renin-angiotensin system (RAS): vasoconstrictor angiotensin-converting enzyme (ACE)/angiotensin II (ANG II)/ANG II type 1 receptor (AT1) axis, and vasodilator ACE type 2 (ACE2)/angiotensin 1-7 (ANG 1-7)/Mas receptor axis, in the development of hypoxic pulmonary hypertension in Ren-2 transgenic rats (TGR). Transgene-negative Hannover Sprague-Dawley (HanSD) rats served as controls. Both TGR and HanSD rats responded to two weeks´ exposure to hypoxia with a significant increase in mean pulmonary arterial pressure (MPAP), however, the increase was much less pronounced in the former. The attenuation of hypoxic pulmonary hypertension in TGR as compared to HanSD rats was associated with inhibition of ACE gene expression and activity, inhibition of AT1 receptor gene expression and suppression of ANG II levels in lung tissue. Simultaneously, there was an increase in lung ACE2 gene expression and activity and, in particular, ANG 1-7 concentrations and Mas receptor gene expression. We propose that a combination of suppression of ACE/ANG II/AT1 receptor axis and activation of ACE2/ANG 1-7/Mas receptor axis of the RAS in the lung tissue is the main mechanism explaining attenuation of hypoxic pulmonary hypertension in TGR as compared with HanSD rats.

scholarly journals Ontogeny of type 1 angiotensin II receptor gene expression in the rat.

1993 ◽  
Vol 91 (2) ◽  
pp. 530-537 ◽  
Author(s):  
A Tufro-McReddie ◽  
J K Harrison ◽  
A D Everett ◽  
R A Gomez
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Receptor Gene ◽  
Angiotensin Ii Receptor ◽  
Receptor Gene Expression

scholarly journals Regulation of angiotensin II type 2 receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

2012 ◽  
Vol 215 (2) ◽  
pp. 291-301 ◽  
Author(s):  
Regina Nostramo ◽  
Andrej Tillinger ◽  
Juan M Saavedra ◽  
Ashok Kumar ◽  
Varunkumar Pandey ◽  
...  
Keyword(s):  
Gene Expression ◽  
Angiotensin Ii ◽  
Receptor Gene ◽  
Receptor Expression ◽  
Mrna Levels ◽  
Ang Ii ◽  
Catecholamine Biosynthesis ◽  
Receptor Mrna ◽  
Receptor Gene Expression

While the renin–angiotensin system is important for adrenomedullary responses to stress, the involvement of specific angiotensin II (Ang II) receptor subtypes is unclear. We examined gene expression changes of angiotensin II type 1A (AT1A) and type 2 (AT2) receptors in rat adrenal medulla in response to immobilization stress (IMO). AT2 receptor mRNA levels decreased immediately after a single 2-h IMO. Repeated IMO also decreased AT2 receptor mRNA levels, but the decline was more transient. AT1A receptor mRNA levels were unaltered with either single or repeated IMO, although binding was increased following repeated IMO. These effects of stress on Ang II receptor expression may alter catecholamine biosynthesis, as tyrosine hydroxylase and dopamine β-hydroxylase mRNA levels in PC12 cells are decreased with Ang II treatment in the presence of ZD7155 (AT1 receptor antagonist) or with CGP42112 (AT2 receptor agonist) treatment. Involvement of stress-triggered activation of the hypothalamic–pituitary–adrenocortical or sympathoadrenal axis in AT2 receptor downregulation was examined. Cultured cells treated with the synthetic glucocorticoid dexamethasone displayed a transcriptionally mediated decrease in AT2 receptor mRNA levels. However, glucocorticoids are not required for the immediate stress-triggered decrease in AT2 receptor gene expression, as demonstrated in corticotropin-releasing hormone knockout (Crh KO) mice and hypophysectomized rats, although they can regulate basal gene expression. cAMP and pituitary adenylate cyclase-activating polypeptide also reduced AT2 receptor gene expression and may mediate this response. Overall, the effects of stress on adrenomedullary AT1A and AT2 receptor expression may contribute to allostatic changes, such as regulation of catecholamine biosynthesis.

Increase of cardiac M2-muscarinic receptor gene expression in type-1 but not in type-2 diabetic rats

2008 ◽  
Vol 441 (2) ◽  
pp. 201-204 ◽  
Author(s):  
Liang-Ming Lee ◽  
Cheng Kuei Chang ◽  
Kai-Chun Cheng ◽  
Dai-Huang Kou ◽  
I-Min Liu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Muscarinic Receptor ◽  
Receptor Gene ◽  
Diabetic Rats ◽  
M2 Muscarinic Receptor ◽  
Receptor Gene Expression ◽  
Type 2 Diabetic
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