Localization of the Angiotensin II Receptor Subtypes in the Human Atrium

Brink, Marijke; Erné, Paul; Gasparo, Marc de; Rogg, H.; Schmid, Andres; Stulz, P; Bullock, Gillian

doi:10.1006/jmcc.1996.0168

Cited by 53 publications

(23 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Total Ang II receptor numbers in LV were in the range of 3.8 to 17.3 fmol/mg protein (Table), similar to the results reported by the previous studies, [13][14][15][16] but were lower than the receptor numbers (118, nϭ5) determined by de Gasparo et al 17,37,38 de Gasparo et al used combined fractions including plasma membranes and internalized receptors, whereas we and other studies [13][14][15][16] measured Ang II receptor numbers using only membrane fractions. In fact, Regitz-Zagrosek et al 14 found that the B max values determined with combined fractions were increased compared with those using only membranes.…”

Section: Discussionsupporting

confidence: 89%

“…localization of AT 2 -R in human atrial tissues 38 or in LV of cardiomyopathic hamsters. 22 Because of limited resolution of the autoradiographic technique and the homogeneous distribution of relatively low-density myocardial Ang II binding sites, the cellular resolution of AT 1 -R and AT 2 -R in the normal or failing myocardium remained unclear.…”

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression

Tsutsumi

Matsubara

Ohkubo

et al. 1998

Circulation Research

217

159

View full text Add to dashboard Cite

Abstract-The expression pattern of angiotensin (Ang) II type 2 receptor (AT 2 -R) in the remodeling process of human left ventricles (LVs) remains poorly defined. We analyzed its expression at protein, mRNA, and cellular levels using autopsy, biopsy, or operation LV samples from patients with failing hearts caused by acute (AMI) or old (OMI) myocardial infarction and idiopathic dilated cardiomyopathy (DCM) and also examined functional biochemical responses of failing hearts to Ang II. In autopsy samples from the nonfailing heart group, the ratio of AT 1 -R and AT 2 -R was 59% and 41%, respectively. The expression of AT 2 -R was markedly increased in DCM hearts at protein (3.5-fold) and mRNA (3.1-fold) levels compared with AMI or OMI. AT 1 -R protein and mRNA levels in AMI hearts showed 1.5-and 2.1-fold increases, respectively, whereas in OMI and DCM hearts, AT 1 -R expression was significantly downregulated. AT 1 -R-mediated response in inositol phosphate production was significantly attenuated in LV homogenate from failing hearts compared with nonfailing hearts. AT 2 -R sites were highly localized in the interstitial region in either nonfailing or failing heart, whereas AT 1 -R was evenly distributed over myocardium at lower densities. Mitogen-activated protein kinase (MAPK) activation by Ang II was significantly decreased in fibroblast compartment from the failing hearts, and pretreatment with AT 2 -R antagonist caused an additional significant increase in Ang II-induced MAPK activity (36%). Cardiac hypertrophy suggested by atrial and brain natriuretic peptide levels was comparably increased in OMI and DCM, whereas accumulation of matrix proteins such as collagen type 1 and fibronectin was much more prominent in DCM than in OMI. These findings demonstrate that (1) AT 2 -R expression is upregulated in failing hearts, and fibroblasts present in the interstitial regions are the major cell type responsible for its expression, (2) AT 2 -R present in the fibroblasts exerts an inhibitory effect on Ang II-induced mitogen signals, and (3) AT 1 -R in atrial and LV tissues was downregulated during chronic heart failure, and AT 1 -R-mediated functional biochemical responsiveness was decreased in the failing hearts. Thus, the expression level of AT 2 -R is likely determined by the extent of interstitial fibrosis associated with heart failure, and the expression and function of AT 1 -R and AT 2 -R are differentially regulated in failing human hearts. (Circ Res. 1998;83:1035-1046.)Key Words: angiotensin II type 2 receptor Ⅲ AT 2 receptor Ⅲ angiotensin II type 1 receptor Ⅲ AT 1 receptor, angiotensin II T he presence of 2 isoforms of angiotensin (Ang) II receptor was originally proposed on the basis of differences in sensitivity of receptor-ligand binding to dithiothreitol. Ang type 2 receptor (AT 2 -R), which is insensitive to dithiothreitol and has a high affinity for PD123319 and CGP42112A, was isolated, and this receptor was shown to have the same seventransmembrane domain of AT 1 -R but only minimal homology (see Review i...

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 99%

Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression

Tsutsumi

Matsubara

Ohkubo

et al. 1998

Circulation Research

217

159

View full text Add to dashboard Cite

show abstract

“…Frozen sections (10 mm) were mounted onto chrome alum-gelatine-coated slides and stored at x20uC for up to 3 months before use. 8 -AII (speci®c activity 81.4 TBq/mmol) for 90 min at 22uC, as described previously [15]. Nonspeci®c binding was de®ned using 1 mmol/L AII.…”

Section: Autoradiographic Studiesmentioning

confidence: 99%

Angiotensin II in child urinary bladder: functional and autoradiographic studies

et al. 2000

View full text Add to dashboard Cite

Objectives To investigate the receptors for angiotensin II (AII, reported to be a potent contractile agent in human urinary bladder), using functional and autoradiographic techniques in child and adult bladder specimens. Materials and methods Bladder specimens were obtained from 61 children (aged 4 months to 12 years) undergoing ureteric reimplantation for vesico-ureteric re¯ux, and from 10 adults undergoing cystectomy. After overnight storage, the mucosa was removed and isometric contractions obtained from detrusor muscle strips in the presence of phosphoramidon (10 mmol/ L). Only one concentration of AII was added to each preparation because of tachyphylaxis.

show abstract

“…The stimulation of AT 2 receptors may aggravate antihypertensive effect by natriuresis, but the role of AT 2 receptor subtype in LVH patients is unknown [12]. The study of renal effect of losartan by Dahlof et al put a hint on its consistent uricosuric effect.…”

Section: Introductionmentioning

confidence: 99%

Assesment of Clinical Effectiveness of Losartan and Amlodipine in Hypertensive Patient With Left Ventricular Hypertrophy

Hameed

Rutuparna

Merin

et al. 2017

Asian J Pharm Clin Res

View full text Add to dashboard Cite

Objective: Hypertension is an important worldwide public health challenge because of its high frequency and concomitant risks of cardiovascular and kidney diseases. Left ventricular hypertrophy (LVH) is defined as an increase in the mass of the LV, which can be secondary to an increase in wall thickness, an increase in cavity size, or both. Relevant study reported that LVH is one of the major and independent risk factors for coronary artery disease, heart failure, serious dysrhythmias, and sudden death. Thus, regression of LVH is a primary pharmacologic objective. The objective of this study is to assess the effectiveness of losartan and amlodipine in regression of LVH and to monitor the adverse effects of these drugs on monotherapy. The study also focused to estimate the clinical effectiveness of specified drugs in lowering hypertension. Methods:The study conducted was retrospective, prospective, comparative study extended over 1 year on 28 patients based on inclusion and exclusion criteria.Results: Both these drugs cause regression of LVH with a decrease in LV mass index value; it is seen that amlodipine is better in controlling elevated blood pressure (BP), especially diastolic BP. In statistical analysis, regression of LVH was found to be correlated with reduction of BP. Conclusion:Incidence of adverse effect was found to be prominent in amlodipine group. Thus, losartan was found to be better in regressing LVH than amlodipine.

show abstract

Localization of the Angiotensin II Receptor Subtypes in the Human Atrium

Cited by 53 publications

References 0 publications

Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression

Angiotensin II Type 2 Receptor Is Upregulated in Human Heart With Interstitial Fibrosis, and Cardiac Fibroblasts Are the Major Cell Type for Its Expression

Angiotensin II in child urinary bladder: functional and autoradiographic studies

Assesment of Clinical Effectiveness of Losartan and Amlodipine in Hypertensive Patient With Left Ventricular Hypertrophy

Contact Info

Product

Resources

About