Selective Expression of Des-Arg9-Br Sensitive (Bi) Receptors in Vivo and in Vitro by Angiotensin Converting Enzyme Inhibitors

Absctract Context In vitro and in vivo evidence has supported the role of angiotensin II blockade in reducing leiomyoma cell proliferation and growth. However, no population-based study to date has investigated this potential association. Objective This work aims to determine whether prior angiotensin-converting enzyme inhibitor (ACEi) use is associated with a reduced odds of leiomyoma development. Design A nested case-control study was conducted. Setting The population was assembled from the Truven Health MarketScan Research Database, which includes private health insurance claims from January 1, 2012 to December 31, 2017. Patients or Other Participants We included (n = 353 917) women age 18 to 65 with hypertension. Cases (n = 13 108) with a leiomyoma diagnosis were matched to controls (n = 340 808) with no such diagnosis at a 1:26 ratio by age and region of origin within the United States. Intervention Prior ACEi use was determined from outpatient drug claims. Main Outcome Measure Leiomyoma development was indicated by a first-time diagnosis code. Results Women on an ACEi experienced a 31.8% reduced odds of developing clinically recognized leiomyoma compared to nonusers (odds ratio [OR] 0.68; 95% CI, 0.65-0.72). This association was significant for each age group: 30 to 39 years (OR 0.86; 95% CI, 0.74-0.99), 40 to 49 years (OR 0.71; 95% CI, 0.66-0.76), 50 to 59 years (OR 0.63; 95% CI, 0.58-0.69), and 60 to 65 years (OR 0.58; 95% CI, 0.50-0.69). Of the ACEis, lisinopril (OR 0.67; 95% CI, 0.64-0.71), quinapril (OR 0.62; 95% CI, 0.41-0.92), and ramipril (OR 0.35; 95% CI, 0.23-0.50) demonstrated a significant association with reduced leiomyoma incidence. Conclusions ACEi use was associated with a reduced odds of developing clinically recognized leiomyoma in adult hypertensive women.

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Angiotensin-converting enzyme inhibitors attenuate propofol-induced pro-oxidative and antifibrinolytic effect in human endothelial cells

Journal of the Renin-Angiotensin-Aldosterone System ◽

10.1177/1470320316687197 ◽

2017 ◽

Vol 18 (1) ◽

pp. 147032031668719 ◽

Cited By ~ 2

Author(s):

Marzena Wojewodzka-Zelezniakowicz ◽

Anna Gromotowicz-Poplawska ◽

Wioleta Kisiel ◽

Emilia Konarzewska ◽

Janusz Szemraj ◽

...

Keyword(s):

Oxidative Stress ◽

Endothelial Cells ◽

Angiotensin Converting Enzyme ◽

Enzyme Inhibitors ◽

Umbilical Vein ◽

Angiotensin Converting Enzyme Inhibitors ◽

Mrna Levels ◽

Converting Enzyme ◽

Converting Enzyme Inhibitors

Introduction: The aim of this study was to investigate the effects of plasma and tissue angiotensin-converting enzyme inhibitors (ACE-Is) against propofol-induced endothelial dysfunction and to elucidate the involved mechanisms in vitro. Materials and methods: We examined the effects of propofol (50 μM), quinaprilat and enalaprilat (10−5 M) on fibrinolysis (t-PA, PAI-1, TAFI antigen levels), oxidative stress parameters (H2O2 and MDA antigen levels and SOD and NADPH oxidase mRNA levels) and nitric oxide bioavailability (NO2/NO3 concentration and NOS expression at the level of mRNA) in human umbilical vein endothelial cells (HUVECs). Results: We found that both ACE-Is promoted similar endothelial fibrinolytic properties and decreased oxidative stress in vitro. Propofol alone increased the release of antifibrinolytic and pro-oxidative factors from the endothelium and increased mRNA iNOS expression. We also found that the incubation of HUVECs in the presence of propofol following ACE-Is pre-incubation caused weakness of the antifibrinolytic and pro-oxidative potential of propofol and this effect was similar after both ACE-Is. Conclusions: This observation suggests that the studied ACE-Is exerted protective effects against endothelial cell dysfunction caused by propofol, independently of hemodynamics.

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Abstract P423: Chronic Doxycycline Administration Inhibits Angiotensin Converting Enzyme Activity and Exerts Antioxidants Effects in Renovascular Hypertensive Rats

Hypertension ◽

10.1161/hyp.70.suppl_1.p423 ◽

2017 ◽

Vol 70 (suppl_1) ◽

Author(s):

Elen Rizzi Sanchez ◽

Giselle F Bonacio ◽

Danielle A Guimaraes ◽

Gustavo Oliveira Paula ◽

Jefferson Henrich Amaral ◽

...

Keyword(s):

Angiotensin Converting Enzyme ◽

Cardiovascular Effects ◽

Angiotensin Converting Enzyme Inhibitors ◽

Converting Enzyme ◽

Hypertensive Rats ◽

Angiotensin I ◽

Converting Enzyme Inhibitors ◽

Ace Activity

Doxycycline (Dox), an established matrix metalloproteinase (MMP) inhibitor, and angiotensin-converting enzyme inhibitors (ACEi) present beneficial cardiovascular effects which could be consequence of their antioxidants properties. Furthermore, some evidences have shown other biochemical similarities between Dox and ACEi suggesting that Dox could also inhibit ACE and ACEi directly interact with MMPs and inhibit these proteases. Supporting this idea, Dox is able to chelate divalent metals, such as calcium and zinc, which are essential for the ACE activity. In this regard, we hypothesized that Dox inhibits ACE activity in hypertensive rats which leads to a reduction in ROS production and decrease hypertension. Sham-operated or 2K1C hypertensive rats were treated with Dox (30 mg/Kg/day) or water for 4 weeks. Systolic blood pressure (SBP) was monitored weekly. Dox treatment reduced SBP in 2K1C rats from 200±12 mmHg to 158±8 mmHg (P<0.05). In addition, Dox treatment attenuated reactive oxygen species (ROS) levels in hypertensive animals measured by lucigenin chemiluminescense (in RLU/mg of aorta: from 711±1.0 to 377±93; P<0.05). ACE activity in aorta was increased in untreated 2K1C rats (22±0.8 nmols/min/g) when compared with the Sham group (12±1.0 nmols/min/g; P<0.05) and Dox treatment was able to reduce ACE activity in 2K1C rats (15±2.0 nmols/min/g; P<0.05). To evaluate whether Dox inhibits ACE activity in vitro , aortic tissues from 2K1C rats were incubated with Dox or Captopril (a known ACEi ). Dox in vitro did not affect ACE activity while captopril inhibited 80% of its activity. To verify whether Dox could inhibit ACE activity in vivo , an acute assay was performed with different doses of angiotensin I (in μg/Kg: 0.03, 0.3 and 3), after the single administration of Dox or saline (i.p.). Angiotensin I infusion increased mean arterial pressure dose-dependently and Dox pretreatment did not attenuated these increases significantly (P>0.05) as Captopril.Taken together, these results show that chronic treatment with Dox inhibits ACE activity in aorta of 2K1C rats, which contribute to ROS reduction and SBP attenuation. However, the mechanism by which Dox inhibits ACE activity needs further investigation.

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