17β-Estradiol downregulates tissue angiotensin-converting enzyme and ANG II type 1 receptor in female rats

2005 ◽  
Vol 288 (3) ◽  
pp. R759-R766 ◽  
Author(s):  
Stephanie A. Dean ◽  
Junhui Tan ◽  
Edward R. O'Brien ◽  
Frans H. H. Leenen
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Abdominal Aorta ◽  
Female Rats ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Ovx Rats ◽  
17Β Estradiol ◽  
Ace Activity ◽  
Critical Components

Estrogens have been implicated in both worsening and protecting from cardiovascular disease. The effects of 17β-estradiol (E2) on the cardiovascular system may be mediated, at least in part, by its modulation of local tissue renin-angiotensin systems (RAS). We assessed two critical components, angiotensin-converting enzyme (ACE) and ANG II type 1 receptor (AT1R), in the heart, lung, abdominal aorta, adrenal, kidney, and brain in four groups of female Wistar rats ( n = 5–6/group): 1) sham ovariectomized, 2) ovariectomized (OVX) treated with subcutaneous vehicle, 3) OVX treated with 25 μg/day (regular) E2 subcutaneously, and 4) OVX treated with 250 μg/day (high) subcutaneous E2 for 2 or 5 wk. After 2 wk, plasma ACE activity was not altered by OVX, but it was 34–38% lower in OVX + regular E2 and OVX + high E2 rats compared with sham OVX rats, and these decreases were no longer present after 5 wk. After 5 wk, OVX alone increased ACE activity and binding densities, and AT1R binding densities by 15–100% in right ventricle, left ventricle (LV), kidney, lung, abdominal aorta, adrenal and several cardiovascular regulatory nuclei in the brain. These effects were, for the most part, prevented by regular E2 replacement and were reversed to decreases by high E2 treatment. This regulation of tissue ACE and AT1R is significant as the activity of these tissue RAS contributes to the pathogenesis and/or progression of hypertension, atherosclerosis, and LV remodeling after myocardial infarction.

Angiotensin-converting enzyme determination in plasma during therapy with converting enzyme inhibitor: two methods compared

1991 ◽  
Vol 37 (8) ◽  
pp. 1390-1393 ◽  
Author(s):  
T P Gorski ◽  
D J Campbell
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Spectrophotometric Method ◽  
Enzyme Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Fluorometric Method ◽  
Converting Enzyme Inhibitor ◽  
Ace Activity

Abstract For normal and above-normal concentrations of angiotensin-converting enzyme (ACE; EC 3.4.15.1) activity in plasma, results of a manual fluorometric method [with hippuryl-histidyl-leucine (HHL), 5 mmol/L, as substrate] correlated well with those of an automated spectrophotometric method [with 3-(2-furylacryloyl)-L-phenylalanyl-glycyl-glycine (FAPGG), 2 mmol/L, as substrate]. However, for patients receiving converting enzyme inhibitor (CEI) therapy, the spectrophotometric method showed much greater suppression of plasma ACE activity than did the fluorometric method. To determine which of the two methods provided a more reliable indication of ACE inhibition in vivo, we measured plasma ACE, angiotensin I (ANG I), and angiotensin II (ANG II) in patients receiving the CEI perindopril. During perindopril therapy, changes in the ratio of ANG II:ANG I, an index of ACE activity in vivo, showed a close agreement with changes in plasma ACE activity measured with FAPGG as substrate, but not with HHL as substrate. We conclude that measurement of ACE activity in vitro with FAPGG as substrate provides a reliable measure of changes in conversion of ANG I to ANG II in vivo during CEI therapy.

scholarly journals Dual RAS blockade normalizes angiotensin-converting enzyme-2 expression and prevents hypertension and tubular apoptosis in Akita angiotensinogen-transgenic mice

2012 ◽  
Vol 302 (7) ◽  
pp. F840-F852 ◽  
Author(s):  
Chao-Sheng Lo ◽  
Fang Liu ◽  
Yixuan Shi ◽  
Hasna Maachi ◽  
Isabelle Chenier ◽  
...  
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Angiotensin Converting Enzyme 2 ◽  
Gene And Protein Expression ◽  
Intrarenal Ras ◽  
Renal Proximal Tubular ◽  
The Right

We investigated the effects of dual renin-angiotensin system (RAS) blockade on angiotensin-converting enzyme-2 (Ace2) expression, hypertension, and renal proximal tubular cell (RPTC) apoptosis in type 1 diabetic Akita angiotensinogen (Agt)-transgenic (Tg) mice that specifically overexpress Agt in their RPTCs. Adult (11 wk old) male Akita and Akita Agt-Tg mice were treated with two RAS blockers (ANG II receptor type 1 blocker losartan, 30 mg·kg−1·day−1) and angiotensin-converting enzyme (ACE) inhibitor perindopril (4 mg·kg−1·day−1) in drinking water. Same-age non-Akita littermates and Agt-Tg mice served as controls. Blood pressure, blood glucose, and albuminuria were monitored weekly. The animals were euthanized at age 16 wk. The left kidneys were processed for immunohistochemistry and apoptosis studies. Renal proximal tubules were isolated from the right kidneys to assess gene and protein expression. Urinary ANG II and ANG 1–7 were quantified by ELISA. RAS blockade normalized renal Ace2 expression and urinary ANG 1–7 levels (both of which were low in untreated Akita and Akita Agt-Tg), prevented hypertension, albuminuria, tubulointerstitial fibrosis and tubular apoptosis, and inhibited profibrotic and proapoptotic gene expression in RPTCs of Akita and Akita Agt-Tg mice compared with non-Akita controls. Our results demonstrate the effectiveness of RAS blockade in preventing intrarenal RAS activation, hypertension, and nephropathy progression in diabetes and support the important role of intrarenal Ace2 expression in modulating hypertension and renal injury in diabetes.

Effect of sex hormones on renal estrogen and angiotensin type 1 receptors in female and male rats

2007 ◽  
Vol 292 (2) ◽  
pp. R794-R799 ◽  
Author(s):  
Jennifer L. Rogers ◽  
Adam R. Mitchell ◽  
Christine Maric ◽  
Kathryn Sandberg ◽  
Adam Myers ◽  
...  
Keyword(s):  
Male Rats ◽  
High Dose ◽  
Sham Operation ◽  
Protective Effects ◽  
Ang Ii ◽  
Intact Male ◽  
Ovx Rats ◽  
17Β Estradiol ◽  
Angiotensin Type

Although the mechanisms are not understood, evidence suggests that 17β-estradiol (E2) confers protection from cardiovascular and renal complications in many diseases. We have reported that E2 decreases angiotensin type 1 receptors (AT1Rs) in different tissues and hypothesize that E2 exerts tonic inhibition on AT1Rs, reducing effects of ANG II. This study determined the effects of E2 and dihydrotestosterone (DHT) on cortical estrogen receptors (ERs) and glomerular AT1R binding in rats. Animals underwent sham operation, ovariectomy (Ovx) or orchidectomy (Cas) and were treated (Ovx ± E2; Cas ± DHT) for 3 wk. Cortical ERα protein was 2.5 times greater, and ERβ was 80% less in females vs. males ( P < 0.01). Glomerular AT1R binding was lower in females than males [4,657 ± 838 vs. 7,457 ± 467 counts per minute (cpm), P < 0.01]. Ovx reduced ERα protein by 50%, whereas E2 increased ERα expression after Ovx. The decrease in cortical ERα in Ovx rats was associated with a significant increase in AT1R binding (6,908 ± 609 cpm), and E2 prevented this increase. There was no change in ERα or AT1R binding following Cas ± DHT (25 mg) treatment, although Cas did elevate cortical ERβ (P < 0.01). Interestingly, the high dose DHT (200 mg) elevated ERα 150% above intact levels and profoundly decreased AT1R binding (1,824 ± 705 cpm, P < 0.001 vs. intact male). This indicates that under normal conditions, glomerular AT1R binding is significantly greater in male than female animals, which may be important in development of cardiovascular and renal disease in males. Furthermore, E2 regulates ERα and is inversely associated with glomerular AT1R binding, supporting our hypothesis that E2 tonically suppresses AT1Rs and suggesting a potential mechanism for the protective effects of estrogen.

Differential ANG II generation in plasma and tissue of mice with decreased expression of the ACE gene

2002 ◽  
Vol 282 (6) ◽  
pp. H2254-H2258 ◽  
Author(s):  
Chih-Chang Wei ◽  
Baohong Tian ◽  
Gilbert Perry ◽  
Qing Cheng Meng ◽  
Yiu-Fai Chen ◽  
...  
Keyword(s):  
Genetic Variation ◽  
Steady State ◽  
Angiotensin Converting Enzyme ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Heterozygous Deletion ◽  
Wild Type ◽  
Vascular Space ◽  
Plasma Angiotensin ◽  
Ace Activity

We utilized mice with homozygous disruption of angiotensin-converting enzyme (ACE) (−/−), mice with heterozygous deletion of ACE (+/−), and wild-type mice (+/+) to test the hypothesis that genetic variation in ACE modulates tissue and plasma angiotensin (ANG) II concentrations. With the use of ANG I as substrate, kidney, heart, and lung ACE activity was reduced 80% in −/− mice compared with +/+ mice. However, ANG II concentrations and ANG II-to-ANG I ratios in the kidney, heart, and lung did not differ among genotypes. In contrast, plasma ANG II concentrations in −/− mice were <2 fmol/ml, whereas plasma ANG I concentrations were extremely high (765 fmol/ml). Chymase activity was increased 14-fold in the kidney ( P < 0.05) and 1.5-fold in the heart ( P < 0.05) of −/− versus +/+ mice but did not differ among genotypes in the lung. ANG II formation from enzymes other than ACE and chymase contributed <2% of total ANG II formation in all genotypes. These data suggest that ACE is essential to ANG II formation in the vascular space, whereas chymase may provide an important mechanism in maintaining steady-state ANG II levels in tissue.

ANG II is involved in the LPS-induced production of proinflammatory cytokines in dehydrated rats

2003 ◽  
Vol 284 (4) ◽  
pp. R1092-R1097 ◽  
Author(s):  
Michio Miyoshi ◽  
Katsumi Nagata ◽  
Toshiaki Imoto ◽  
Osamu Goto ◽  
Akiko Ishida ◽  
...  
Keyword(s):  
Plasma Concentration ◽  
Angiotensin Converting Enzyme ◽  
Receptor Antagonist ◽  
Proinflammatory Cytokines ◽  
Ace Inhibitor ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Single Intravenous Injection

We have previously reported results that led us to speculate that ANG II is involved in the LPS-induced production of proinflammatory cytokines, especially under dehydrated conditions. To test this possibility, in this study we examined the effects of an angiotensin-converting enzyme (ACE) inhibitor and an antagonist of the type-1 ANG II receptor (AT1 receptor) on the LPS-induced production of the proinflammatory cytokines IL-1 and IL-6 in dehydrated rats. A single intravenous injection of LPS induced a marked increase in the expression of IL-1β mRNA in the liver, an effect that was significantly attenuated by pretreatment with the ACE inhibitor. Furthermore, the ACE inhibitor reduced the LPS-induced increase in the hepatic concentration of IL-1β protein. When the AT1-receptor antagonist was given intravenously before the LPS, the increase in the hepatic concentration of IL-1β was significantly reduced. Finally, the ACE inhibitor reduced the LPS-induced increase in the plasma concentration of IL-6. These results represent the first in vivo evidence that ANG II and its AT1 receptor play important roles in the production of proinflammatory cytokines that is induced by LPS under dehydrated conditions.

Altered angiotensin-converting enzyme in lung and extrapulmonary tissues of hypoxia-adapted rats

1988 ◽  
Vol 65 (1) ◽  
pp. 218-227 ◽  
Author(s):  
S. Oparil ◽  
A. J. Narkates ◽  
R. M. Jackson ◽  
H. S. Ann
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Active Sites ◽  
Chronic Hypoxia ◽  
Plasma Renin ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypoxia Exposure ◽  
Catalytically Active ◽  
Tissue Homogenates ◽  
Ace Activity

The effects of exposing rats to hypoxia (10% O2) at normal atmospheric pressure for periods of 14 or 28 days on angiotensin-converting enzyme (ACE) activity and stores of angiotensin I (ANG I) and angiotensin II (ANG II) in lung, kidney, brain, and testis were examined. ACE activity was measured by spectrophotometric assay, and active sites of ACE were estimated by measuring the binding of 125I-351A [N-(1-carbonyl-3-phenyl-propyl)-L-lysyl-L-proline], a highly specific active site-directed inhibitor of ACE, to tissue homogenates and perfused lungs. Hypoxia exposure produced progressive reductions in ACE activity in lung homogenates and in ACE inhibitor binding to perfused lungs. ANG II levels in lungs from hypoxia-adapted animals were significantly less than air controls, suggesting that the reduction in intrapulmonary ACE activity was associated with reduced local generation of ANG II. ACE activity was increased in kidney and unchanged in brain and testis of hypoxia-adapted rats compared with air controls. Thus the effects of chronic hypoxia on catalytically active ACE and ACE active sites in the intact animal were organ specific. Adaptation to chronic hypoxia did not significantly alter plasma renin activity or ANG I or ANG II levels or serum ACE content. The hypoxia-induced alterations in lung and kidney ACE were reversible after return to a normoxic environment.

Effect of long-term treatment with urocortin on the activity of somatic angiotensin-converting enzyme in spontaneously hypertensive rats

2010 ◽  
Vol 88 (2) ◽  
pp. 168-176 ◽  
Author(s):  
Cui Yang ◽  
Xiuxia Liu ◽  
Shengnan Li
Keyword(s):  
Angiotensin Converting Enzyme ◽  
Spontaneously Hypertensive Rats ◽  
Term Treatment ◽  
Ang Ii ◽  
Converting Enzyme ◽  
Hypertensive Rats ◽  
Spontaneously Hypertensive ◽  
Long Term Treatment ◽  
Ace Activity

Our previous acute study on urocortin (Ucn) demonstrated that Ucn altered serum and tissue angiotensin-converting enzyme (ACE) activity in rats. Therefore, the present investigation was designed to explore the effect of long-term treatment with Ucn on somatic ACE (sACE) and other components of the renin–angiotensin system (RAS). After 8 weeks of intravenous administration of Ucn in spontaneously hypertensive rats (SHR), serum and tissue sACE, angiotensin II (Ang II), nitric oxide (NO), Ang-(1–7), and tissue chymase activities were evaluated. RT-PCR analysis was performed to determine the quantity of tissue sACE mRNA. Serum sACE activity was reduced by Ucn, although tissue sACE activity and tissue sACE mRNA were elevated. Chymase activity was observed to be enhanced by Ucn, whereas the ACE inhibitor enalapril failed to influence chymase. Serum and tissue Ang II activity was reduced, but NO and Ang-(1–7) production was increased in a concentration-dependent manner after Ucn treatment. Meanwhile, a significant decrease of the systolic blood pressure (SBP) was observed after the long-term Ucn administration, and there was a significant positive correlation (r2 = 0.6993) between serum ACE activity and SBP. Pretreatment with the corticotropin-releasing factor (CRF) blocker astressin and the extracellular signal-regulated kinase 1/2 (ERK1/2) pathway blocker PD98059 abolished these effects of Ucn. Our findings further support the hypothesis that the changes of sACE activity and the production of other RAS components may play roles in the vasodilatory property of Ucn via the activation of the ERK1/2 pathway.

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