Proceedings of the Symposium ‘Angiotensin AT1 Receptors: From Molecular Physiology to Therapeutics’: HUMAN TYPE-1 ANGIOTENSIN II (AT1) RECEPTOR GENE STRUCTURE AND FUNCTION

Regulatory actions of angiotensin II (AngII), which is involved in the pathophysiology of hypertension and also participates in cell proliferation and cell differentiation, are mainly mediated by AngII type 1 (AT1) receptor. Recently, activating mutations of receptors causing hyperfunctioning endocrine diseases have been described in the case of the TSH and LH receptors, implicating that such mutations might occur in other G-protein-coupled receptors. Furthermore it seems to be possible that genetic variations of AT1 receptor have an influence upon the action of AngII. Therefore, we searched by sequence analysis of the coding region of AT1 receptor gene for activating mutations and genetic polymorphisms in 56 human adrenal tumors (16 aldosterone-producing adenomas, 10 cortisol-producing adenomas, 1 aldosterone-producing carcinoma, and 29 incidentalomas). We were not able to identify any activating mutation in the coding region of AT1 receptor gene. We conclude that activating mutations of the AT1 receptor are not a major cause of the development of adrenal adenomas, if at all. In addition, polymorphic subtypes of AT1 receptor do not seem to play a major role in the pathogenesis of these tumors, even though a tendency towards a higher frequency of the polymorphic base substitution at position 573 (T573-->C) in cortisol-producing tumors needs to be further evaluated.

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Hypercholesterolemia is associated with enhanced angiotensin AT1-receptor expression

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1997.272.6.h2701 ◽

1997 ◽

Vol 272 (6) ◽

pp. H2701-H2707 ◽

Cited By ~ 36

Author(s):

G. Nickenig ◽

O. Jung ◽

K. Strehlow ◽

O. Zolk ◽

W. Linz ◽

...

Keyword(s):

New Zealand ◽

Angiotensin Ii ◽

Radioligand Binding ◽

Receptor Gene ◽

Density Lipoprotein ◽

At1 Receptor ◽

Receptor Expression ◽

At1 Receptors ◽

New Zealand White Rabbits

Low-density lipoprotein increases the AT1-receptor gene expression in vascular smooth muscle cells. To elucidate whether elevated cholesterol serum levels upregulate the AT1 receptor and its functional response to angiotensin II in vivo, we compared 1) the vasoconstrictive effect of angiotensin II and 2) the level of expression of the vascular AT1 receptor in aortas of normocholesterolemic and hypercholesterolemic rabbits. Contraction experiments on isolated aortic rings showed that the angiotensin II-induced vasoconstriction was increased in hypercholesterolemic New Zealand White rabbits compared with normocholesterolemic New Zealand White rabbits. This difference in the angiotensin II-induced vasoconstriction was caused by a twofold increase in the density of cell surface AT1 receptors in hypercholesterolemic rabbits, as assessed by radioligand binding assays. The enhanced expression of AT1 receptors on the surface of these vascular cells was caused by elevated steady-state levels of the AT1-receptor mRNA to 220 +/- 35% in aortas excised from hypercholesterolemic rabbits compared with levels in aortas from normocholesterolemic rabbits, as measured by Northern blot analysis. These data indicate that hypercholesterolemia is associated with upregulation of expression and function of vascular AT1 receptors in vivo. This suggests a novel mechanism by which hypercholesterolemia could be involved in the onset and progression of chronic vascular diseases such as hypertension and arteriosclerosis if the phenomenon is confirmed in humans.

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Genetic Polymorphisms of the Angiotensin II type 1 (AT1) Receptor Gene

European Heart Journal ◽

10.1093/eurheartj/15.suppl_d.108 ◽

1994 ◽

Vol 15 (suppl D) ◽

pp. 108-112 ◽

Cited By ~ 12

Author(s):

A. Rolfs ◽

I. Weber-Rolfs ◽

V. Regitz-Zagrosek ◽

H. Kallisch ◽

K. Riedel ◽

...

Keyword(s):

Angiotensin Ii ◽

Genetic Polymorphisms ◽

Receptor Gene ◽

At1 Receptor

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Molecular Analysis of the Structure and Function of the Angiotensin II Type 1 Receptor

Hypertension Research ◽

10.1291/hypres.26.937 ◽

2003 ◽

Vol 26 (12) ◽

pp. 937-943 ◽

Cited By ~ 80

Author(s):

Shin-ichiro MIURA ◽

Keijiro SAKU ◽

Sadashiva S KARNIK

Keyword(s):

Angiotensin Ii ◽

Molecular Analysis ◽

Structure And Function ◽

And Function

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Localization of angiotensin-II type 1(AT1) receptors on buffalo spermatozoa: AT1 receptor activation during capacitation triggers rise in cyclic AMP and calcium

Molecular Biology Reports ◽

10.1007/s11033-014-3043-7 ◽

2014 ◽

Vol 41 (4) ◽

pp. 1959-1965 ◽

Cited By ~ 2

Author(s):

Sivaram Vedantam ◽

Rita Rani ◽

Monica Garg ◽

Suresh K. Atreja

Keyword(s):

Angiotensin Ii ◽

Cyclic Amp ◽

Receptor Activation ◽

At1 Receptor ◽

At1 Receptors

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Enhanced hemodynamic responses to angiotensin II in diabetes are associated with increased expression and activity of AT1 receptors in the afferent arteriole

Physiological Genomics ◽

10.1152/physiolgenomics.00025.2017 ◽

2017 ◽

Vol 49 (10) ◽

pp. 531-540 ◽

Cited By ~ 10

Author(s):

Jie Zhang ◽

Helena Y. Qu ◽

Jiangping Song ◽

Jin Wei ◽

Shan Jiang ◽

...

Keyword(s):

Angiotensin Ii ◽

Mrna Level ◽

At1 Receptor ◽

Receptor Expression ◽

Ang Ii ◽

Diabetic Mice ◽

At1 Receptors ◽

Enhanced Expression ◽

Bolus Intravenous Injection

The prevalence of hypertension is about twofold higher in diabetic than in nondiabetic subjects. Hypertension aggravates the progression of diabetic complications, especially diabetic nephropathy. However, the mechanisms for the development of hypertension in diabetes have not been elucidated. We hypothesized that enhanced constrictive responsiveness of renal afferent arterioles (Af-Art) to angiotensin II (ANG II) mediated by ANG II type 1 (AT1) receptors contributes to the development of hypertension in diabetes. In response to an acute bolus intravenous injection of ANG II, alloxan-induced diabetic mice exhibited a higher mean arterial pressure (MAP) (119.1 ± 3.8 vs. 106.2 ± 3.5 mmHg) and a lower renal blood flow (0.25 ± 0.07 vs. 0.52 ± 0.14 ml/min) compared with nondiabetic mice. In response to chronic ANG II infusion, the MAP measured with telemetry increased by 55.8 ± 6.5 mmHg in diabetic mice, but only by 32.3 ± 3.8 mmHg in nondiabetic mice. The mRNA level of AT1 receptor increased by ~10-fold in isolated Af-Art of diabetic mice compared with nondiabetic mice, whereas ANG II type 2 (AT2) receptor expression did not change. The ANG II dose-response curve of the Af-Art was significantly enhanced in diabetic mice. Moreover, the AT1 receptor antagonist, losartan, blocked the ANG II-induced vasoconstriction in both diabetic mice and nondiabetic mice. In conclusion, we found enhanced expression of the AT1 receptor and exaggerated response to ANG II of the Af-Art in diabetes, which may contribute to the increased prevalence of hypertension in diabetes.

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