scholarly journals Recombinant Expression and Characterization of Human and Murine ACE2: Species-Specific Activation of the Alternative Renin-Angiotensin-System

2012 ◽  
Vol 2012 ◽  
pp. 1-8 ◽  
Author(s):  
Marko Poglitsch ◽  
Oliver Domenig ◽  
Cornelia Schwager ◽  
Stefan Stranner ◽  
Bernhard Peball ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Recombinant Expression ◽  
Renin Angiotensin System ◽  
Functional Connection ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor ◽  
Conversion Rates ◽  
Species Specific

Angiotensin-converting enzyme 2 (ACE2) is a monocarboxypeptidase of the renin-angiotensin-system (RAS) which is known to cleave several substrates among vasoactive peptides. Its preferred substrate is Angiotensin II, which is tightly involved in the regulation of important physiological functions including fluid homeostasis and blood pressure. Ang 1–7, the main enzymatic product of ACE2, became increasingly important in the literature in recent years, as it was reported to counteract hypertensive and fibrotic actions of Angiotensin II via the MAS receptor. The functional connection of ACE2, Ang 1–7, and the MAS receptor is also referred to as the alternative axis of the RAS. In the present paper, we describe the recombinant expression and purification of human and murine ACE2 (rhACE2 and rmACE2). Furthermore, we determined the conversion rates of rhACE2 and rmACE2 for different natural peptide substrates in plasma samples and discovered species-specific differences in substrate specificities, probably leading to functional differences in the alternative axis of the RAS. In particular, conversion rates of Ang 1–10 to Ang 1–9 were found to be substantially different when applying rhACE2 or rmACE2in vitro. In contrast to rhACE2, rm ACE2 is substantially less potent in transformation of Ang 1–10 to Ang 1–9.

Effect of digoxin on the in vitro secretion of renin and angiotensin II/III immunoreactivity by the human adrenal gland

1992 ◽  
Vol 127 (3) ◽  
pp. 210-214 ◽  
Author(s):  
Matteo Pistorello ◽  
Margherita Cimolato ◽  
Francesco Pedini ◽  
Donatella Piovan ◽  
Marco Boscaro ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Adrenal Gland ◽  
Renin Angiotensin System ◽  
Aldosterone Secretion ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Superfusion System ◽  
Sustained Reduction ◽  
High Doses

Cardiac glycosides in man inhibit renin secretion, probably through a direct effect at the renal level (i.e. inhibition of juxtaglomerular cell Na/K ATPase). Since there is evidence that the human adrenal possesses an intrinsic renin-angiotensin system, we investigated the effect of digoxin on the in vitro generation of renin and angiotensin II/III, as well as of aldosterone, by the human adrenal gland. Minced normal adrenal tissues were studied in a superfusion system, measuring in the 15-min superfusate fractions active renin by immunoradiometric assay and angiotensin II/III and aldosterone by radioimmunoassay, respectively. In a first set of four experiments using different concentrations of digoxin in sequence for 45 min periods, digoxin 10−5, but not 10−8 and 10−6 mol/l, significantly reduced renin and angiotensin II/III output from adrenals, while no change in aldosterone was observed. In a second set of three experiments, the addition of digoxin 10−5 mol/l for 120 min caused a sustained reduction of renin and angiotensin II/III, but not of aldosterone. In the final experiment, the decrease of renin and angiotensin II/III during superfusion with digoxin 10−5 mol/l was significantly greater than that observed during superfusion with digoxin in the presence of antidigoxin antibodies. Our data indicate that digoxin at high doses reduces renin and angiotensin II/III but not aldosterone secretion by the human adrenal gland. This suggests two different effects of digoxin, probably both mediated by inhibition of the Na/K ATPase activity, on the adrenal renin-angiotensin- and aldosterone-secreting cells.

Presence of cellular renin-angiotensin system in chromaffin cells of bovine adrenal medulla

2002 ◽  
Vol 283 (5) ◽  
pp. H1811-H1818 ◽  
Author(s):  
Jun Ming Wang ◽  
Dirk Slembrouck ◽  
Junhui Tan ◽  
Lut Arckens ◽  
Frans H. H. Leenen ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Angiotensin Converting Enzyme ◽  
Adrenal Medulla ◽  
Chromaffin Cells ◽  
Renin Angiotensin System ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Bovine Chromaffin Cells

The presence of a local renin-angiotensin system has been established in organs that serve as angiotensin targets. In this study, the expression of angiotensinogen mRNA and subcellular localization of renin, angiotensin-converting enzyme, and angiotensin II were investigated in bovine adrenal medullary cells in primary culture. By light microscopy, expression of angiotensinogen mRNA, immunoreactive renin, angiotensin-converting enzyme, and angiotensin II were readily detectable only in the chromaffin cells. The density distribution of renin and angiotensin II in sucrose gradients suggested a concentration in chromaffin granules, a localization directly confirmed by immunoelectron microscopy. Reverse transcriptase-polymerase chain reaction and sequencing confirmed the expression of angiotensinogen in bovine chromaffin cells and the adrenal medulla. In addition, in vitro autoradiography indicated that both angiotensin-converting enzyme and angiotensin type 1 receptors were present in the adrenal medulla. These results provide the first direct evidence that chromaffin cells in the adrenal medulla are not only the target for angiotensin but should also be considered as potential local angiotensin-generating and -storing cells.

Role of angiotensin II in endothelial dysfunction induced by lipopolysaccharide in mice

2007 ◽  
Vol 293 (6) ◽  
pp. H3726-H3731 ◽  
Author(s):  
Donald D. Lund ◽  
Robert M. Brooks ◽  
Frank M. Faraci ◽  
Donald D. Heistad
Keyword(s):  
Oxidative Stress ◽  
Angiotensin Ii ◽  
Endothelial Dysfunction ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Disease States ◽  
Vasomotor Function

Endotoxin [or lipopolysaccharide (LPS)] increases levels of superoxide in blood vessels and impairs vasomotor function. Angiotensin II plays an important role in the generation of superoxide in several disease states, including hypertension and heart failure. The goal of this study was to determine whether the activation of the renin-angiotensin system contributes to oxidative stress and endothelial dysfunction after endotoxin. We examined the effects of enalapril (an angiotensin-converting enzyme inhibitor) or L-158809 (an angiotensin receptor blocker) on increases of superoxide and vasomotor dysfunction in mice treated with LPS. C57BL/6 mice were treated with either enalapril (60 mg·kg−1·day−1) or L-158809 (30 mg·kg−1·day−1) for 4 days. After the third day, LPS (10–20 mg/kg) or vehicle was injected intraperitoneally, and one day later, vasomotor function of the aorta was examined in vitro. After precontraction with PGF2α, the maximal responses to sodium nitroprusside were similar in the aorta from normal and LPS-treated mice. In contrast, the relaxation to acetylcholine was impaired after LPS (54 ± 5% at 10−5, mean ± SE) compared with vessels treated with vehicle (88 ± 1%; P < 0.05). Enalapril improved ( P < 0.05) relaxation in response to acetylcholine to 81 ± 6% after LPS. L-158809 also improved relaxation in response to acetylcholine to 77 ± 4% after LPS. Superoxide (measured with lucigenin and hydroethidine) was increased ( P < 0.05) in aorta after LPS, and levels were reduced ( P < 0.05) following enalapril and L-158809. Thus, after LPS, enalapril and L-158809 reduce superoxide levels and improve relaxation to acetylcholine in the aorta. The findings suggest that activation of the renin-angiotensin system contributes importantly to oxidative stress and endothelial dysfunction after endotoxin.

Preovulatory changes in the angiotensin II system in bovine follicles

2013 ◽  
Vol 25 (3) ◽  
pp. 539 ◽  
Author(s):  
Lucas C. Siqueira ◽  
Joabel T. dos Santos ◽  
Rogério Ferreira ◽  
Robson Souza dos Santos ◽  
Adelina M. dos Reis ◽  
...  
Keyword(s):  
Angiotensin Ii ◽  
Granulosa Cells ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Ang Ii ◽  
Hormone Production ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Theca Cells

The present study evaluated whether the gonadotrophin surge modulates components of the renin–angiotensin system and whether angiotensin II (Ang II) plays a role in the production of hormones by follicular cells during the ovulatory process. In Experiment 1, cows were ovariectomised at various times (0, 3, 6, 12 and 24h) after GnRH injection to obtain preovulatory follicles. The concentration of Ang II in follicular fluid increased after GnRH and reached a peak at 24h, concomitant with the peak of angiotensinogen (AGT) mRNA expression in granulosa cells. AGT mRNA was not expressed in theca cells. Ang II receptor type 2 and angiotensin-converting enzyme mRNA levels were transiently upregulated in theca cells. In Experiment 2, an in vitro culture was used to determine whether Ang II could modulate hormone production by healthy dominant follicles. In the absence of LH, Ang II did not alter hormonal production by either theca or granulosa cells. Ang II plus LH increased progesterone and prostaglandin secretion by granulosa cells. In summary, the renin–angiotensin system is actively controlled during the preovulatory period and Ang II amplifies the stimulatory effects of LH on the secretion of progesterone and prostaglandins by granulosa cells.

Physical Exercise and ACE2-Angiotensin-(1-7)-Mas Receptor Axis of the Renin Angiotensin System

2017 ◽  
Vol 24 (9) ◽  
Author(s):  
Albena Nunes-Silva ◽  
Guilherme Carvalho Rocha ◽  
Daniel Massote Magalhaes ◽  
Lucas Neves Vaz ◽  
Marcelo Henrique Salviano de Faria ◽  
...  
Keyword(s):  
Physical Exercise ◽  
Renin Angiotensin System ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Mas Receptor
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