Tissue specific expression of vascular smooth muscle angiotensin II receptor subtypes during ovine pregnancy

1996 ◽  
Vol 271 (1) ◽  
pp. H212-H221 ◽  
Author(s):  
B. E. Cox ◽  
C. R. Rosenfeld ◽  
J. E. Kalinyak ◽  
R. R. Magness ◽  
P. W. Shaul
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Specific Expression ◽  
At1 Receptors ◽  
Mammary Arteries ◽  
At2 Receptors

Uteroplacentral responses to infused angiotensin II (ANG II) are less than those elicited by systemic vasculature. This does not reflect ANG II receptor (AT) downregulation but may reflect differences in AT-receptor subtypes expressed. We examined AT-receptor subtypes in smooth muscle (SM) from uterine (UA), mesenteric, renal, and mammary arteries and aorta from nulliparous (n = 12), pregnant (n = 18; 105-140 days, term = 145 days), postpartum (n = 5; 6-9 days after delivery), and nonpregnant parous (n = 14) ewes by assessing displacement of 125I-labeled ANG II binding by [Sar1, Ile8]ANG II (AT1 and AT2), losartan (AT1) PD-123319 (AT2), and CGP-42112A (AT2). AT2 receptors accounted for 75-90% of total binding in UA. Except for mammary arteries, other arteries expressed only AT1 receptors. Receptor subtype expression was not altered by reproductive state in any artery studied. With the use of autoradiography, AT2 receptors appear to predominate in media of small intramyometrial arteries, whereas AT1 receptors predominate in the luminal portion. We therefore determined which subtype mediates endothelium-derived ANG II-induced increases in UA PGI2 synthesis during pregnancy. ANG II (0.05 microM) increased PGI2 synthesis 62%, from 214 +/- 13 to 346 +/- 23 pg.mg-1.h-1 (P < 0.05). Losartan (1.0 microM) inhibited the rise in PGI2 (257 +/- 24 vs. 238 +/- 25 pg.mg-1.h-1), whereas 1.0 microM PD-123319 had no effect (231 +/- 23 vs. 337 +/- 31 pg.mg-1.h-1; P < 0.05). AT2 receptors do not mediate ANG II-induced vasoconstriction, thus differences in uteroplacental and systemic sensitivity to ANG II may reflect predominance of AT2 receptors in UASM and ANG II-induced increases in UA prostacyclin synthesis by endothelial AT1 receptors.

Characterization and development of angiotensin II receptor subtypes (AT1 and AT2) in rat brain

1991 ◽  
Vol 261 (1) ◽  
pp. R209-R216 ◽  
Author(s):  
K. Tsutsumi ◽  
J. M. Saavedra
Keyword(s):  
Angiotensin Ii ◽  
Rat Brain ◽  
Limbic System ◽  
Receptor Subtypes ◽  
Angiotensin Ii Receptor ◽  
At1 Receptors ◽  
Young Rats ◽  
Angiotensin Ii Receptor Subtypes ◽  
Old Rats ◽  
At2 Receptors

Angiotensin II receptor subtypes (AT1 and AT2) were characterized in rat brain by displacement with the specific angiotensin antagonists Du Pont 753 and CGP 42112A, respectively, and quantitative autoradiography. Young (2-wk-old) rats expressed AT1 receptors in selected limbic system areas, structures involved in cardiovascular and fluid regulation, parts of the hippocampal formation, and the choroid plexus. In young rats, AT2 receptors were concentrated in areas involved in control and learning of motor activity, sensory areas, and selected limbic system structures. The cingulate cortex, the molecular layer of the cerebellar cortex, and the superior colliculus contained both AT1 and AT2 receptors. The number of AT1 receptors in most areas of adult (8-wk-old) rats was similar to or even higher than that present in young rats. Conversely, AT2 receptors were always much lower in number in adult animals, and in some areas they were undetectable in adults. Their differential localization and development suggest different functions for the specific angiotensin II receptor subtypes.

Angiotensin II-receptor stimulation of cytosolic calcium concentration in cultured renal resistance arterioles

1996 ◽  
Vol 271 (6) ◽  
pp. F1239-F1247 ◽  
Author(s):  
Z. Zhu ◽  
W. J. Arendshorst
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Vascular Reactivity ◽  
Calcium Concentration ◽  
Morphological Properties ◽  
Free Calcium ◽  
Functional Coupling ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Angiotensin Ii Receptor

This study provides an initial characterization of basic morphological properties of cultures of vascular smooth muscle cells (VSMC) from rat preglomerular resistance vessels and of the functional coupling of angiotensin II (ANG II) receptors to cytosolic free calcium concentration ([Ca2+]i (fura 2 fluorescence photometry). Renal VSMC were isolated from interlobular arteries and afferent arterioles (< 50 microns) using an iron oxide sieving method and compared with rat aortic VSMC cultured under similar conditions. Quiescent monolayers maintained uniform morphology and [Ca2+]i signaling profile between passages 3 and 10. Arteriolar and aortic VSMC were spindle shaped and expressed smooth muscle-specific alpha-actin and myosin heavy chains SM-1 and SM-2. ANG II caused a rapid increase in [Ca2+]i, followed by a sustained plateau phase at 50-60% of the peak value. The initial maximum [Ca2+]i responses were dose dependent and of similar magnitude in renal arteriolar and aortic VSMC. ANG II (10(-7) M) increased [Ca2+]i from 50 to 240 nM in arteriolar and from 57 to 201 nM in aortic VSMC (P < 0.001 for both). Inhibition of ANG II effects on [Ca2+]i revealed significant signaling through distinct AT-receptor subtypes (losartan and PD-123319 sensitive) in renal arteriolar VSMC. In contrast, only losartan was effective in aortic VSMC. The AT2-receptor ligand CGP-42112 had no effect in either vessel type. Our results demonstrate that cultured arteriolar VSMC have anatomical similarities to aortic VSMC and functional differences in AT-receptor signaling in response to ANG II. This novel preparation should provide a useful approach with which to investigate cellular mechanisms concerning receptor coupling to signaling pathways involved in vascular reactivity of arteriolar VSMC in the microcirculation in general and the kidney in particular.

Glomerular angiotensin II receptor subtypes during development of rat kidney

1993 ◽  
Vol 265 (2) ◽  
pp. F264-F271 ◽  
Author(s):  
G. M. Ciuffo ◽  
M. Viswanathan ◽  
A. M. Seltzer ◽  
K. Tsutsumi ◽  
J. M. Saavedra
Keyword(s):  
Angiotensin Ii ◽  
Kidney Development ◽  
Developmental Stages ◽  
Rat Kidney ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Kidney Medulla ◽  
At1 Receptors ◽  
Old Rats

We used quantitative autoradiography to investigate distribution of angiotensin II (ANG II) receptor subtypes during development of the kidney in the rat. In fetal, newborn, and 3-day-old rats, immature glomeruli in the form of comma and S-shaped bodies, located in the nephrogenic zone of the renal cortex, expressed only the angiotensin AT2 receptor subtype. Conversely, the juxtamedullary glomeruli, in more advanced developmental stages, expressed only the AT1 subtype. Similarly, maturing and fully developed glomeruli, present in 1-, 2-, and 8-wk-old rats, expressed only AT1 receptors. In the kidney medulla, there was a similar change in ANG II receptor subtype expression, with the AT2 subtype expressed earlier and the AT1 subtype later during development. Our results demonstrate a selective expression of ANG II receptor subtypes during kidney development. We have found glomerular and medullary AT1 receptors only at developmental stages when kidney function has matured. Conversely, AT2 receptors are expressed only in immature structures, suggesting that they may have a role during kidney organogenesis.

scholarly journals Angiotensin II receptor subtypes on adrenal adenoma in primary hyperaldosteronism.

1993 ◽  
Vol 4 (1) ◽  
pp. 111-116
Author(s):  
M D Cook ◽  
M I Phillips ◽  
V I Cook ◽  
B Kimura ◽  
C S Wilcox
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Receptor Antagonist ◽  
Receptor Binding ◽  
Adrenal Adenoma ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
At1 Receptors ◽  
High Concentrations ◽  
At2 Receptors

Patients with an aldosterone-producing adenoma (APA) characteristically fail to show an increase in plasma aldosterone (PA) concentration with maneuvers that increase angiotensin II (Ang II), yet they retain a brisk response of PA to adrenocorticotrophic hormone. Therefore, adrenal Ang II receptor binding was characterized in a patient with APA who had a blocked PA response to Ang II infusion before adrenalectomy. The binding of [125I]Sar1,IIe5-Ang II in adrenal gland and tumor was fully displaced by excess Ang II. In the tumor, 98% of [125I]Sar1,IIe5-Ang II binding was displaced by the AT, receptor antagonist losartan, yet only 5% was displaced by the AT2 receptor antagonist PD-123,319. Autoradiography of the adrenal gland itself showed a predominance of AT1 receptors in the cortex and AT2 receptors in the medulla. The tumor showed a predominance of AT1 receptors, but there was some evidence of a limited population of AT2 receptors. The tumor and adjacent adrenal contained high concentrations of Ang II. In conclusion, a defect in Ang II-stimulated aldosterone secretion in APA occurs despite high concentrations of Ang II in the adrenal and the presence of specific, high-affinity Ang II receptor binding sites.

scholarly journals Expression of type 1 angiotensin II receptor subtypes and angiotensin II-induced calcium mobilization along the rat nephron.

1997 ◽  
Vol 8 (11) ◽  
pp. 1658-1667 ◽  
Author(s):  
N Bouby ◽  
A Hus-Citharel ◽  
J Marchetti ◽  
L Bankir ◽  
P Corvol ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Collecting Duct ◽  
At1 Receptor ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Thick Ascending Limb ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Nephron Segments

The localization of two type 1 angiotensin II receptor subtype mRNA, AT1A and AT1B, was determined by reverse transcription-PCR on microdissected glomeruli and nephron segments. The coupling sensitivity of these two receptor subtypes was evaluated by measuring variations in intracellular calcium ([Ca2+]i) elicited by angiotensin II (Ang II) in structures expressing either AT1A or AT1B mRNA, using Fura-2 fluorescence. The highest expression of AT1 mRNA was found in glomerulus, proximal tubule, and thick ascending limb. In glomerulus, AT1A and AT1B mRNA were similarly expressed, whereas in all nephron segments AT1A mRNA expression was dominant (approximately 84%). The increase in [Ca2+]i elicited by 10(-7) mol/L Ang II was highest in proximal segments (delta [Ca2+]i is approximately equivalent to 300 to 400 nmol/L) and thick ascending limb (delta [Ca2+]i is approximately equivalent to 200 nmol/L). In glomerulus and collecting duct, the response was lower (delta < 100 nmol/L). The median effective concentrations for Ang II were of the same order of magnitude in glomerulus (12.2 nmol/L), in which both AT1A and AT1B are expressed, and in cortical thick ascending limb (10.3 nmol/ L), in which AT1A is almost exclusively expressed. The Ang II-induced calcium responses were totally abolished by the AT1 receptor antagonist losartan (1 mumol/L) but not by the AT2 antagonist PD 123319 (1 mumol/L). In the absence of external Ca2+, the peak phase of the response induced by 10(-7) mol/L Ang II was reduced and shortened, suggesting that a part of the [Ca2+]i increase originated from the mobilization of the intracellular Ca2+ pool. In conclusion, these results demonstrate that in the rat kidney: (1) AT1A is the predominant AT1 receptor subtype expressed in the nephron segments, (2) glomerulus is the only structure with a relatively high AT1B mRNA content, and (3) AT1A and AT1B receptor subtypes do not differ in their efficiency for the activation of calcium second-messenger system.

Nephrogenesis and angiotensin II receptor subtypes gene expression in the fetal lamb

1998 ◽  
Vol 274 (6) ◽  
pp. F1062-F1069 ◽  
Author(s):  
Valérie Gimonet ◽  
Laurence Bussieres ◽  
Anissa A. Medjebeur ◽  
Bernard Gasser ◽  
Brigitte Lelongt ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Mrna Expression ◽  
Mesangial Cells ◽  
Temporal Distribution ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Developmental Study ◽  
Ang Ii ◽  
Angiotensin Ii Receptor ◽  
Fetal Lamb

To investigate the role of angiotensin II (ANG II) in nephrogenesis, a developmental study of renal AT1 and AT2 receptor mRNA expression was performed in parallel with the quantitative and qualitative analysis of metanephros development in fetal lamb from 60 to 140 days of gestation. Both ANG II receptor subtypes were expressed early during nephrogenesis but displayed specific spatial and temporal distribution during gestation. High-AT2 mRNA expression took place in the outermost nephrogenic area and in the undifferentiated mesenchymal cells surrounding the ampulla; level of AT2 expression in this localization followed closely glomeruli proliferation rate and disappeared after nephrogenesis completion (>120 days). AT2 mRNA was also detected in the differentiated epithelial cells of macula densa of maturing glomeruli. Although most of AT1 mRNA labeling was found in the mesangial cells of maturing glomeruli, where it persisted after nephrogenesis completion, additional labeling was found in undifferentiated cells, in cells invading the inferior cleft of S-shaped bodies (80 days), and in medullar cells between tubules (120 days). Our results suggest that each receptor subtype has a specific role in renal morphogenesis, i.e., AT2 in mesenchymal proliferation or apoptosis and AT1 in vascular smooth muscle cells differentiation.

scholarly journals Regulation of angiotensin II receptors and extracellular matrix turnover in human retinal pigment epithelium: role of angiotensin II

2008 ◽  
Vol 295 (6) ◽  
pp. C1633-C1646 ◽  
Author(s):  
Gary E. Striker ◽  
Francoiçe Praddaude ◽  
Oscar Alcazar ◽  
Scott W. Cousins ◽  
Maria E. Marin-Castaño
Keyword(s):  
Extracellular Matrix ◽  
Angiotensin Ii ◽  
Type Iv Collagen ◽  
Pigment Epithelium ◽  
Receptor Expression ◽  
Age Related Macular Degeneration ◽  
Receptor Subtype ◽  
Receptor Subtypes ◽  
Ang Ii ◽  
Type Iv

The early stage of age-related macular degeneration (AMD) is characterized by the formation of subretinal pigment epithelium (RPE) deposits as a result of the dysregulation in the turnover of extracellular matrix (ECM) molecules. However, the mechanism involved remains unclear. Hypertension (HTN) is an important risk factor for AMD, and angiotensin II (ANG II) is the most important hormone associated with HTN. However, the relevance of ANG II receptors and ANG II effects on RPE have not been investigated yet. Therefore, the expression and regulation of ANG II receptors as well as the ECM turnover were studied in human RPE. ANG II receptors were expressed and upregulated by ANG II in human RPE. This regulation resulted in functional receptor expression, since an increase in intracellular concentration of calcium was observed upon ANG II stimulation. ANG II also increased matrix metalloproteinase (MMP)-2 activity and MMP-14 at the mRNA and protein levels as well as type IV collagen degradation. These ANG II effects were abolished in the presence of the ANG II receptor subtype 1 (AT1) receptor antagonist candesartan. In contrast, ANG II decreased type IV collagen via both AT1 and AT2 receptors, suggesting a synergistic effect of the two receptor subtypes. In conclusion, we have confirmed the presence of ANG II receptors in human RPE and their regulation by ANG II as well as the regulation of ECM molecules via ANG II receptors. Our data support the hypothesis that ANG II may exert biological function in RPE through ANG II receptors and that ANG II may cause dysregulation of molecules that play a major role in the turnover of ECM in RPE basement membrane and Bruch's membrane, suggesting a pathogenic mechanism to explain the link between HTN and AMD.

Upregulation of angiotensin II type 2 receptor expression in estrogen-induced pituitary hyperplasia

2004 ◽  
Vol 286 (5) ◽  
pp. E786-E794 ◽  
Author(s):  
Cecilia Suarez ◽  
Graciela Díaz-Torga ◽  
Arturo González-Iglesias ◽  
Carolina Cristina ◽  
Damasia Becu-Villalobos
Keyword(s):  
Angiotensin Ii ◽  
Receptor Expression ◽  
Receptor Subtype ◽  
At2 Receptor ◽  
Ang Ii ◽  
Pituitary Hyperplasia ◽  
Releasing Effect ◽  
At2 Receptors

Recent evidence shows that reexpression and upregulation of angiotensin II (ANG II) type 2 (AT2) receptor in adult tissues occur during pathological conditions such as tissue hyperplasia, inflammation, and remodeling. In particular, expression of functional AT2 receptors in the pituitary and their physiological significance and regulation have not been described. In this study, we demonstrate that chronic in vivo estrogen treatment, which induces pituitary hyperplasia, enhances local AT2 expression (measured by Western blot and RT-PCR) concomitantly with downregulation of ANG II type 1 (AT1) receptors. In vivo progesterone treatment of estrogen-induced pituitary hyperplasia did not modify either the ANG II receptor subtype expression pattern or octapeptide-induced and AT1-mediated calcium signaling. Nevertheless, an unexpected potentiation of the ANG II prolactin-releasing effect was observed in this group, and this response was sensitive to both AT1 and AT2 receptor antagonists. These data are the first to document that ANG II can act at the pituitary level through the AT2 receptor subtype and that estrogens display a differential regulation of AT1 and AT2 receptors at this level.

Angiotensin II AT2 receptor inhibits smooth muscle cell migration via fibronectin cell production and binding

2002 ◽  
Vol 282 (4) ◽  
pp. C654-C664 ◽  
Author(s):  
Catherine Chassagne ◽  
Christophe Adamy ◽  
Philippe Ratajczak ◽  
Bruno Gingras ◽  
Emmanuel Teiger ◽  
...  
Keyword(s):  
Smooth Muscle ◽  
Angiotensin Ii ◽  
Smooth Muscle Cell ◽  
Muscle Cell ◽  
Vascular Function ◽  
Cell Attachment ◽  
Smooth Muscle Actin ◽  
Inhibitory Effect ◽  
Receptor Subtype ◽  
Ang Ii

To explore the vascular function of the angiotensin II (ANG II) AT2receptor subtype (AT2R), we generated a vascular smooth muscle cell (SMC) line expressing the AT2R (SMC-vAT2). The involvement of AT2R in the motility response of SMCs was examined in SMC-vAT2 cells and their controls (SMC-v) cultured on either laminin or fibronectin matrix proteins with the agarose drop technique. All experiments were conducted in the presence of a saturating concentration of losartan to inactivate the AT1R subtype. Under basal conditions, both cell lines migrated outside drops, but on laminin only. Treatment with ANG II significantly inhibited the migration of SMC-vAT2but not SMC-v cells, and this effect was prevented by the AT2R antagonist CGP-42112A. The decreased migration of SMC-vAT2 was not associated with changes in cell growth, cytoskeleton stiffness, or smooth muscle actin, desmin, and tenascin expression. However, it was correlated with increased synthesis and binding of fibronectin. Both responses were prevented by incubation with selective AT2R antagonists. Addition of GRGDTP peptide, which prevents cell attachment of fibronectin, reversed the AT2R inhibitory effect on SMC-vAT2 migration. These results suggest that activated ANG II AT2R inhibits SMC migration via cellular fibronectin synthesis and associated cell binding.

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