Estrogen Deficiency and Colonic Function: Surgical Menopause and Sex Differences in Angiotensin and Dopamine Receptor Interaction

Receptor Expression ◽

Oxidative Markers ◽

Mutual Regulation ◽

Inflammatory Processes ◽

Abstract The physiopathological mechanisms that regulate menopausal and sex differences in colonic transit, inflammatory processes, and efficacy of treatments have not been clarified. The dopaminergic system and renin–angiotensin system coexist in the gut and regulate different processes such as motility, absorption/secretion, and inflammation. We investigated the changes in expression of major angiotensin and dopamine receptors in the colon of male, female, and ovariectomized female mice. Possible interaction between both systems was investigated using male and female mice deficient (ko) for major angiotensin and dopamine receptors. In wild-type mice, colonic tissue from females showed lower angiotensin type 1/angiotensin type 2 ratio (an index of pro-inflammatory/anti-inflammatory renin–angiotensin system balance), lower dopamine D1 and D2 receptor expression, and lower levels of pro-inflammatory and pro-oxidative markers relative to males. Interestingly, ovariectomy increased the expression of pro-inflammatory angiotensin type 1 receptor expression and decreased anti-inflammatory angiotensin type 2 receptor expression, increased D1 and D2 receptor expression, and increased the levels of pro-inflammatory and pro-oxidative markers. Ovariectomy-induced changes were blocked by estrogen replacement. The present results suggest a mutual regulation between colonic angiotensin and dopamine receptors and sex differences in this mutual regulation. Estrogen regulates changes in both angiotensin and dopamine receptor expression, which may be involved in sex- and surgical menopause-related effects on gut motility, permeability, and vulnerability to inflammatory processes.

154 Effects of raloxifene, tamoxifene and ?-oestradiol on angiotensin type 1 receptor expression in human umbilical artery endothelial cells incubated with high concentrations of glucose

European Heart Journal ◽

10.1016/s0195-668x(03)93699-2 ◽

2003 ◽

Vol 24 (5) ◽

pp. 14

Author(s):

T FRANCUZ

Keyword(s):

Endothelial Cells ◽

Umbilical Artery ◽

Receptor Expression ◽

Human Umbilical Artery ◽

High Concentrations ◽

Abstract 309: Sp-3 But not the NF-kB Transcription Factor Causes the Up-regulation of Angiotensin Type 1 Receptor Expression and Contributes to Hypertension in Aging FBN rats.

Hypertension ◽

10.1161/hyp.64.suppl_1.309 ◽

2014 ◽

Vol 64 (suppl_1) ◽

Author(s):

Mohammad Saleem ◽

Mohammad Asghar

Keyword(s):

Blood Pressure ◽

Transcription Factors ◽

At1 Receptor ◽

Receptor Expression ◽

Receptor Protein ◽

Receptor Function ◽

Receptor Mrna ◽

Hk2 Cells ◽

We recently reported that age-associated oxidative stress is causal to higher renal angiotensin Type 1 (AT1) receptor function and hypertension in aged Fisher 344 X Brown Norway (FBN) rats. We became interested in examining the mechanism of higher AT1 receptor function in the aging kidneys. Adult (3-month) and aging (21 month) FBN rats were subjected to conscious blood pressure measurement by telemetry approach. The levels of AT1 receptor mRNA in the kidney cortex was measured by qRT-PCR while nuclear Sp-3 and NF-kB-p65 redox-sensitive transcription factors were determined by western blotting. We found that blood pressure was higher in aged than in adult rats (adult vs. old: 110±1 vs. 130±1 mmHg) which was associated with higher AT1 receptor mRNA levels (adult vs. old: 1.51±0.72 vs. 7.86±1.03 DU), and nuclear levels of both Sp-3 (adult vs. old: 0.56±.01 vs. 1.54±.02 DU) and NF-kB-p65 (adult vs. old: 0.9±.01 vs. 1.5±0.01 DU). To further delineate whether sp-3 or NF-kB-p65 or both transcription factors are responsible for the up-regulation of AT1 receptor, human kidney (HK2) cells were transfected with Sp-3 and NF-kB-p65 plasmids. We found that Sp-3 plasmid but not NF-κB-p65 plasmid transfection caused an increase in the levels of AT1 receptor protein in HK2 cells (control vs. transfected: 135±22 vs. 235±10 DU). Furthermore, Sp-3 siRNA treatment resulted in the reduction of Sp-3 (control vs. transfected: 136±10 vs. 93±21 DU) and AT1 receptor protein levels (control vs. transfected: 270±38 vs. 172±201 DU) in HK2 cells. Our results suggest that sp-3 but not the NF-κB-p65 is involved in the up-regulation of renal AT1 receptor that may be contributing to hypertension in aging FBN rats.

Interaction between Angiotensin Type 1, Type 2, and Mas Receptors to Regulate Adult Neurogenesis in the Brain Ventricular–Subventricular Zone

Cells ◽

10.3390/cells8121551 ◽

2019 ◽

Vol 8 (12) ◽

pp. 1551 ◽

Cited By ~ 9

Author(s):

Maria Garcia-Garrote ◽

Ana Perez-Villalba ◽

Pablo Garrido-Gil ◽

German Belenguer ◽

Juan A. Parga ◽

...

Keyword(s):

Adult Neurogenesis ◽

Subventricular Zone ◽

Functional Dependence ◽

At1 Receptor ◽

Receptor Expression ◽

At2 Receptor ◽

The renin–angiotensin system (RAS), and particularly its angiotensin type-2 receptors (AT2), have been classically involved in processes of cell proliferation and maturation during development. However, the potential role of RAS in adult neurogenesis in the ventricular-subventricular zone (V-SVZ) and its aging-related alterations have not been investigated. In the present study, we analyzed the role of major RAS receptors on neurogenesis in the V-SVZ of adult mice and rats. In mice, we showed that the increase in proliferation of cells in this neurogenic niche was induced by activation of AT2 receptors but depended partially on the AT2-dependent antagonism of AT1 receptor expression, which restricted proliferation. Furthermore, we observed a functional dependence of AT2 receptor actions on Mas receptors. In rats, where the levels of the AT1 relative to those of AT2 receptor are much lower, pharmacological inhibition of the AT1 receptor alone was sufficient in increasing AT2 receptor levels and proliferation in the V-SVZ. Our data revealed that interactions between RAS receptors play a major role in the regulation of V-SVZ neurogenesis, particularly in proliferation, generation of neuroblasts, and migration to the olfactory bulb, both in young and aged brains, and suggest potential beneficial effects of RAS modulators on neurogenesis.

Regulation of central angiotensin type 1 receptors and sympathetic outflow in heart failure

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.00073.2009 ◽

2009 ◽

Vol 297 (5) ◽

pp. H1557-H1566 ◽

Cited By ~ 72

Author(s):

Irving H. Zucker ◽

Harold D. Schultz ◽

Kaushik P. Patel ◽

Wei Wang ◽

Lie Gao

Keyword(s):

Oxidative Stress ◽

Heart Failure ◽

Transcription Factor ◽

Critical Role ◽

Good Evidence ◽

Receptor Expression ◽

Ventrolateral Medulla ◽

Sympathetic Outflow ◽

Angiotensin type 1 receptors (AT1Rs) play a critical role in a variety of physiological functions and pathophysiological states. They have been strongly implicated in the modulation of sympathetic outflow in the brain. An understanding of the mechanisms by which AT1Rs are regulated in a variety of disease states that are characterized by sympathoexcitation is pivotal in development of new strategies for the treatment of these disorders. This review concentrates on several aspects of AT1R regulation in the setting of chronic heart failure (CHF). There is now good evidence that AT1R expression in neurons is mediated by activation of the transcription factor activator protein 1 (AP-1). This transcription factor and its component proteins are upregulated in the rostral ventrolateral medulla of animals with CHF. Because the increase in AT1R expression and transcription factor activation can be blocked by the AT1R antagonist losartan, a positive feedback mechanism of AT1R expression in CHF is suggested. Oxidative stress has also been implicated in the regulation of receptor expression. Recent data suggest that the newly discovered catabolic enzyme angiotensin-converting enzyme 2 (ACE2) may play a role in the modulation of AT1R expression by altering the balance between the octapeptide ANG II and ANG- (1–7). Finally, exercise training reduces both central oxidative stress and AT1R expression in animals with CHF. These data strongly suggest that multiple central and peripheral influences dynamically alter AT1R expression in CHF.

Brain angiotensin type 1 receptor expression and function in the Zucker obese rat

Neuroscience Letters ◽

10.1016/s0304-3940(00)00855-7 ◽

2000 ◽

Vol 281 (2-3) ◽

pp. 139-142 ◽

Cited By ~ 8

Author(s):

Harshad S Bokil ◽

James P Porter

Keyword(s):

Receptor Expression ◽

And Function ◽

Intrarenal mouse renin-angiotensin system during ANG II-induced hypertension and ACE inhibition

AJP Renal Physiology ◽

10.1152/ajprenal.00477.2009 ◽

2010 ◽

Vol 298 (1) ◽

pp. F150-F157 ◽

Cited By ~ 48

Author(s):

Romer A. Gonzalez-Villalobos ◽

Ryousuke Satou ◽

Naro Ohashi ◽

Laura C. Semprun-Prieto ◽

Akemi Katsurada ◽

...

Keyword(s):

Ace Inhibition ◽

Ang Ii ◽

Male Mice ◽

Rt Pcr ◽

Angiotensin System ◽

Renin Angiotensin ◽

Induced Hypertension ◽

Angiotensin-converting enzyme (ACE) inhibition (ACEi) ameliorates the development of hypertension and the intrarenal ANG II augmentation in ANG II-infused mice. To determine if these effects are associated with changes in the mouse intrarenal renin-angiotensin system, the expression of angiotensinogen (AGT), renin, ACE, angiotensin type 1 receptor (AT1R) mRNA (by quanitative RT-PCR) and protein [by Western blot (WB) and/or immunohistochemistry (IHC)] were analyzed. C57BL/6J male mice (9–12 wk old) were distributed as controls ( n = 10), ANG II infused (ANG II = 8, 400 ng·kg−1·min−1 for 12 days), ACEi only (ACEi = 10, lisinopril, 100 mg/l), and ANG II infused + ACEi (ANG II + ACEi = 11). When compared with controls (1.00), AGT protein (by WB) was increased by ANG II (1.29 ± 0.13, P < 0.05), and this was not prevented by ACEi (ACEi + ANG II, 1.31 ± 0.14, P < 0.05). ACE protein (by WB) was increased by ANG II (1.21 ± 0.08, P < 0.05), and it was reduced by ACEi alone (0.88 ± 0.07, P < 0.05) or in combination with ANG II (0.80 ± 0.07, P < 0.05). AT1R protein (by WB) was increased by ANG II (1.27 ± 0.06, P < 0.05) and ACEi (1.17 ± 0.06, P < 0.05) but not ANG II + ACEi [1.15 ± 0.06, not significant (NS)]. Tubular renin protein (semiquantified by IHC) was increased by ANG II (1.49 ± 0.23, P < 0.05) and ACEi (1.57 ± 0.15, P < 0.05), but not ANG II + ACEi (1.10 ± 0.15, NS). No significant changes were observed in AGT, ACE, or AT1R mRNA. In summary, reduced responses of intrarenal tubular renin, ACE, and the AT1R protein to the stimulatory effects of chronic ANG II infusions, in the presence of ACEi, are associated with the effects of this treatment to ameliorate augmentations in blood pressure and intrarenal ANG II content during ANG II-induced hypertension.

Improved Glucose-Stimulated Insulin Secretion by Selective Intraislet Inhibition of Angiotensin II Type 1 Receptor Expression in Isolated Islets of db/db Mice

International Journal of Endocrinology ◽

10.1155/2013/319586 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 8

Author(s):

Zhen Zhang ◽

Chunyan Liu ◽

Zhenhua Gan ◽

Xinyi Wang ◽

Qiuyan Yi ◽

...

Keyword(s):

Insulin Secretion ◽

Angiotensin Ii ◽

Mrna Level ◽

Glucose Stimulated Insulin Secretion

Glucagon Secretion ◽

Receptor Expression ◽

Isolated Islets ◽

Expression Level ◽

Recent evidence supported the presence of a local renin-angiotensin system (RAS) in the pancreas, which is implicated in many physiological and pathophysiological processes. We utilized small interfering RNA (siRNA) to investigate the effects of angiotensin II type 1 receptor (AT1R) knockdown on glucose-stimulated insulin secretion (GSIS) in isolated islets of db/db mice and to explore the potential mechanisms involved. We found that Ad-siAT1R treatment resulted in a significant decrease both in AT1R mRNA level and in AT1R protein expression level. With downexpression of AT1R, notable increased insulin secretion and decreased glucagon secretion levels were found by perifusion. Simultaneously, significant increased protein levels of IRS-1 (by 85%), IRS-2 (by 95%), PI3K(85) (by 112.5%), and p-Akt2 (by 164%) were found by western blot. And upregulation of both GLUT-2 (by 190%) and GCK (by 121%) was achieved after AT1R inhibition by Ad-siAT1R. Intraislet AT1R expression level is a crucial physiological regulator of insulin sensitivity ofβcell itself and thus affects glucose-induced insulin and glucagon release. Therefore, the characteristics of AT1R inhibitors could make it a potential novel therapeutics for prevention and treatment of type 2 diabetes.