-
Journal of Hypertension Jun 2020
Topics: Angiotensins; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Hypertension; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32371812
DOI: 10.1097/HJH.0000000000002468 -
Journal of Hypertension Jun 2020
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Betacoronavirus; COVID-19; Coronavirus; Coronavirus Infections; Humans; Pandemics; Pneumonia, Viral; SARS-CoV-2
PubMed: 32371811
DOI: 10.1097/HJH.0000000000002469 -
British Medical Journal Dec 1964
Topics: Angiotensins; Animals; Blood Vessels; Catheterization; Dogs; Femoral Artery; Hypertension; Hypertension, Renal; Kidney; Liver; Portal Vein; Renal Veins; Renin; Research; Splenic Vein
PubMed: 14214191
DOI: 10.1136/bmj.2.5423.1507 -
American Journal of Physiology.... Jan 2014This review describes the changes that occur in circulating renin-angiotensin-aldosterone system (RAAS) components in human pregnancy. These changes depend on endocrine... (Review)
Review
This review describes the changes that occur in circulating renin-angiotensin-aldosterone system (RAAS) components in human pregnancy. These changes depend on endocrine secretions from the ovary and possibly the placenta and decidua. Not only do these hormonal secretions directly contribute to the increase in RAAS levels, they also cause physiological changes within the cardiovascular system and the kidney, which, in turn, induce reflex release of renal renin. High levels of ANG II play a critical role in maintaining circulating blood volume, blood pressure, and uteroplacental blood flow through interactions with the ANG II type I receptor and through increased production of downstream peptides acting on a changing ANG receptor phenotype. The increase in ANG II early in gestation is driven by estrogen-induced increments in angiotensinogen (AGT) levels, so there cannot be negative feedback leading to reduced ANG II production. AGT can exist in various forms in terms of redox state or complexed with other proteins as polymers; these affect the ability of renin to cleave ANG I from AGT. Thus, during pregnancy the rate of ANG I production varies not only because levels of renin change in response to homeostatic demand but also because AGT changes not only in concentration but in form. Activation of the circulating and intrarenal RAASs is essential for normal pregnancy outcome subserving the increased demand for salt and, hence, water during pregnancy. Thus, the complex integration of the secretions and actions of the circulating maternal renin-angiotensin system in pregnancy plays a key role in pregnancy outcome.
Topics: Aldosterone; Angiotensins; Female; Humans; Pregnancy; Renin; Renin-Angiotensin System
PubMed: 24089380
DOI: 10.1152/ajpregu.00034.2013 -
Journal of Hepatology Sep 2007Angiotensin-converting enzyme 2 (ACE2), its product, angiotensin-(1-7) and its receptor, Mas, may moderate the adverse effects of angiotensin II in liver disease. We...
BACKGROUND/AIMS
Angiotensin-converting enzyme 2 (ACE2), its product, angiotensin-(1-7) and its receptor, Mas, may moderate the adverse effects of angiotensin II in liver disease. We examined the expression of these novel components of the renin angiotensin system (RAS) and the production and vasoactive effects of angiotensin-(1-7) in the bile duct ligated (BDL) rat.
METHODS
BDL or sham-operated rats were sacrificed at 1, 2, 3 and 4 weeks. Tissue and blood were collected for gene expression, enzyme activity and peptide measurements. In situ perfused livers were used to assess angiotensin peptide production and their effects on portal resistance.
RESULTS
Hepatic ACE2 gene and activity (P<0.0005), plasma angiotensin-(1-7) (P<0.0005) and Mas receptor expression (P<0.01) were increased following BDL compared to shams. Perfusion experiments confirmed that BDL livers produced increased angiotensin-(1-7) (P<0.05) from angiotensin II and this was augmented (P<0.01) by ACE inhibition. Whilst angiotensin II increased vasoconstriction in cirrhotic livers, angiotensin-(1-7) had no effect on portal resistance.
CONCLUSIONS
RAS activation in chronic liver injury is associated with upregulation of ACE2, Mas and hepatic conversion of angiotensin II to angiotensin-(1-7) leading to increased circulating angiotensin-(1-7). These results support the presence of an ACE2-angiotensin-(1-7)-Mas axis in liver injury which may counteract the effects of angiotensin II.
Topics: Angiotensin I; Angiotensin-Converting Enzyme 2; Angiotensins; Animals; Bile Ducts; Gene Expression; In Vitro Techniques; Ligation; Liver; Liver Cirrhosis, Biliary; Liver Cirrhosis, Experimental; Male; Peptide Fragments; Peptidyl-Dipeptidase A; Portal Vein; Proto-Oncogene Mas; Proto-Oncogene Proteins; Rats; Rats, Sprague-Dawley; Receptor, Angiotensin, Type 1; Receptors, G-Protein-Coupled; Up-Regulation; Vasoconstriction
PubMed: 17532087
DOI: 10.1016/j.jhep.2007.03.008 -
Biochemical and Biophysical Research... Oct 2019Angiotensin processing peptidases (carboxypeptidase A (CPA) and chymase) are stored in cardiac mast cell (MC) secretory granules in large quantity and are co-released...
Angiotensin processing peptidases (carboxypeptidase A (CPA) and chymase) are stored in cardiac mast cell (MC) secretory granules in large quantity and are co-released into the extracellular environment after activation/degranulation. In the human heart, chymase is primarily responsible for angiotensin II (Ang II) generation from the alternate substrate angiotensin-(1-12) (Ang-(1-12)). We investigated the individual and combined hydrolytic specificity of CPA and chymase enzymes (1:1 and 1:⅓ ratio) in the processing of the human Ang-(1-12) (hAng-(1-12)) substrate. To determine the K and V, the CPA and recombinant human chymase (rhChymase) enzymes were incubated with increasing concentrations of hAng-(1-12) substrate (0-300 μM). We found that CPA alone sequentially metabolized hAng-(1-12) substrate into angiotensin-(1-9) (Ang-(1-9), 53%), Ang II (22%) and angiotensin-(1-7) (Ang-(1-7), 11%) during a 15 min incubation. In the presence of rhChymase alone, I-hAng-(1-12) was directly metabolized into Ang II (89%) and no further hydrolysis of Ang II was detected. In the presence of both CPA + rhChymase enzymes (1:1 or 1:⅓ ratio), the amount of Ang II formation from I-hAng-(1-12) within a 5 min incubation period were 68% or 65%, respectively. In the presence of both (CPA + rhChymase), small amounts of Ang-(1-9) and Ang-(1-7) were generated from I-hAng-(1-12). The K and V values were 150 ± 5 μM and 384 ± 23 nM/min/mg of CPA and 40 ± 9 μM and 116 ± 20 nM/min/mg of rhChymase. The catalytic efficiency (V/K ratio) was higher for rhChymase/hAng-(1-12) compared to CPA/hAng-(1-12). Compared to CPA, chymase has a much higher affinity to hydrolyze the hAng-(1-12) substrate directly into Ang II. In addition, Ang II and Ang-(1-7) are the end products of chymase and CPA, respectively. Overall, our findings suggest that the Ang II generation from hAng-(1-12) is primarily mediated by chymase rather than CPA.
Topics: Amino Acid Sequence; Angiotensin I; Angiotensinogen; Angiotensins; Animals; Carboxypeptidases A; Chymases; Humans; Hydrolysis; Mast Cells; Myocardium; Peptide Fragments; Recombinant Proteins; Substrate Specificity; alpha 1-Antitrypsin
PubMed: 31466718
DOI: 10.1016/j.bbrc.2019.08.098 -
Journal of the American Heart... Aug 2018Background In pregnancy, a high plasma volume maintains uteroplacental perfusion and prevents placental ischemia, a condition linked to elevated maternal blood pressure...
Background In pregnancy, a high plasma volume maintains uteroplacental perfusion and prevents placental ischemia, a condition linked to elevated maternal blood pressure ( BP ). Reducing BP by increasing Na intake via plasma volume expansion appears contra-intuitive. We hypothesize that an appropriate Na intake in pregnancy reduces maternal BP and adapts the renin-angiotensin system in a pregnancy-specific manner. Methods and Results BP was measured by implanted telemetry in Sprague-Dawley rats before and throughout pregnancy. Pregnant and nonpregnant animals received either a normal-salt (0.4%; NS ), high-salt (8%; HS ), or low-salt (0.01%; LS ) diet, or HS (days 1-14) followed by LS (days 14-20) diet ( HS / LS ). Before delivery (day 20), animals were euthanized and organs collected. Food, water, and Na intake were monitored in metabolic cages, and urinary creatinine and Na were analyzed. Na intake and retention increased in pregnancy ( NS , LS ), leading to a positive Na balance ( NS , LS ). BP was stable during LS , but reduced in HS conditions in pregnancy. The renin-angiotensin system was adapted as expected. Activating cleavage of α- and γ-subunits of the renal epithelial Na channel and expression of-full length medullary β-subunits, accentuated further in all LS conditions, were upregulated in pregnancy. Conclusions Pregnancy led to Na retention adapted to dietary changes. HS exposure paradoxically reduced BP . Na uptake while only modestly linked to the renin-angiotensin system is enhanced in the presence of posttranslational renal epithelial Na channel modifications. This suggests (1) storage of Na in pregnancy upon HS exposure, bridging periods of LS availability; and (2) that potentially non-renin-angiotensin-related mechanisms participate in EN aC activation and consecutive Na retention.
Topics: Angiotensins; Animals; Blood Pressure; Diet, Sodium-Restricted; Drinking Behavior; Eating; Epithelial Sodium Channels; Female; Kidney; Peptidyl-Dipeptidase A; Pregnancy; RNA, Messenger; Rats; Rats, Sprague-Dawley; Receptors, Angiotensin; Renin-Angiotensin System; Sodium, Dietary; Telemetry; Water; Water-Electrolyte Balance
PubMed: 30371243
DOI: 10.1161/JAHA.117.008363 -
Nephron 2020Here, we review the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, including acute kidney injury, and examine the potential effects of... (Review)
Review
Here, we review the most recent findings on the effects of SARS-CoV-2 infection on kidney diseases, including acute kidney injury, and examine the potential effects of ARBs on the outcomes of patients with COVID-19. Lastly, we discuss the clinical management of COVID-19 patients with existing chronic renal disorders, particularly those in dialysis and with kidney transplants.
Topics: Angiotensin Receptor Antagonists; Angiotensin-Converting Enzyme 2; Angiotensin-Converting Enzyme Inhibitors; Angiotensins; Betacoronavirus; COVID-19; Coronavirus Infections; Humans; Kidney; Kidney Diseases; Kidney Transplantation; Nephrologists; Pandemics; Peptidyl-Dipeptidase A; Pneumonia, Viral; Renal Dialysis; SARS-CoV-2; Virus Replication
PubMed: 32203970
DOI: 10.1159/000507305 -
Peptides Mar 2022We engineered a monoclonal antibody (mAb) against the human C-terminus of angiotensin-(1-12) [h-Ang-(1-12)] and performed a biochemical characterization in concert with...
We engineered a monoclonal antibody (mAb) against the human C-terminus of angiotensin-(1-12) [h-Ang-(1-12)] and performed a biochemical characterization in concert with direct in vivo and ex vivo (carotid artery strips) assessments of h-Ang-(1-12) vasoconstrictor activity in 78 (36 females) transgenic rats expressing the human angiotensinogen gene [TGR(hAGT)L1623] and 26 (10 female) Sprague Dawley (SD) controls. The mAb shows high specificity in neutralizing angiotensin II formation from h-Ang-(1-12) and did not cross-react with human and rat angiotensins. Changes in arterial pressure and heart rate in Inactin® hydrate anesthetized rats were measured before and after h-Ang-(1-12) injections [dose range: 75-300 pmol/kg i.v.] prior to and 30-60 minutes after administration of the h-Ang-(1-12) mAb. Neutralization of circulating Ang-(1-12) inhibited the pressor action of h-Ang-(1-12), prevented Ang-(1-12) constrictor responses in carotid artery rings in both SD and TGR(hAGT)L1623 rats, and caused a fall in the arterial pressure of male and female transgenic rats. The Ang-(1-12) mAb did not affect the response of comparable dose-related pressor responses to Ang II, pre-immune IgG, or the rat sequence of Ang-(1-12). This h-Ang-(1-12) mAb can effectively suppress the pressor actions of the substrate in the circulation of hypertensive rats or in carotid artery strips from both SD and transgenic rats. The demonstration that this Ang-(1-12) mAb by itself, induced a fall in arterial pressure in transgenic hypertensive rats supports further exploring the potential abilities of Ang-(1-12) mAb in the treatment of hypertension.
Topics: Angiotensin I; Angiotensin II; Angiotensinogen; Animals; Antibodies, Monoclonal; Blood Pressure; Female; Humans; Hypertension; Male; Peptide Fragments; Rats; Rats, Sprague-Dawley
PubMed: 34933010
DOI: 10.1016/j.peptides.2021.170714 -
Histochemistry and Cell Biology May 2017The renal tissular renin-angiotensin and bradykinin-kallikrein systems control kidney function together with the renal sympathetic innervation but their interaction is...
The renal tissular renin-angiotensin and bradykinin-kallikrein systems control kidney function together with the renal sympathetic innervation but their interaction is still unclear. To further elucidate this relationship, we investigated these systems in rats 6 days after left kidney denervation (DNX, n = 8) compared to sham-operated controls (CTR, n = 8). Plasma renin concentration was unchanged in DNX vs. CTR (p = NS). Kidney bradykinin (BK) and angiotensin (Ang) I and II concentrations decreased bilaterally in DNX vs. CTR rats (~20 to 40%, p < 0.05) together with Ang IV and V concentrations that were extremely low (p = NS). Renin, Ang III and dopamine concentrations decreased by ~25 to 50% and norepinephrine concentrations by 99% in DNX kidneys (p < 0.05) but were unaltered in opposite kidneys. Ang II/I and KA were comparable in DNX, contralateral and CTR kidneys. Ang III/II increased in right vs. DNX or CTR kidneys (40-50%, p < 0.05). Ang II was mainly located in tubular epithelium by immunocytological staining and its cellular distribution was unaffected by DNX. Moreover, the angiotensinergic and catecholaminergic innervation of right kidneys was unchanged vs. CTR. We found an important dependency of tissular Ang and BK levels on the renal innervation that may contribute to the resetting of kidney function after DNX. The DNX-induced peptide changes were not readily explained by kidney KA, renin or plasma Ang I generation. However, tissular peptide metabolism and compartmentalization may have played a central role. The mechanisms behind the concentration changes remain unclear and deserve further clarification.
Topics: Angiotensins; Animals; Bradykinin; Denervation; Kallikreins; Kidney; Male; Rats; Rats, Wistar; Renin
PubMed: 28220244
DOI: 10.1007/s00418-017-1543-y