Renal renin-angiotensin system in diabetes: functional, immunohistochemical, and molecular biological correlations

1993 ◽  
Vol 265 (4) ◽  
pp. F477-F486 ◽  
Author(s):  
S. Anderson ◽  
F. F. Jung ◽  
J. R. Ingelfinger
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Hydraulic Pressure ◽  
Ang Ii ◽  
Glomerular Injury ◽  
Renal Vasculature ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ace Activity ◽  
Immunohistochemical Studies

Recent evidence indicates a role for the renin-angiotensin system (RAS) in the pathogenesis of glomerular injury in diabetes. To further explore the RAS in diabetes, studies were conducted in nondiabetic control rats and in moderately hyperglycemic diabetic (DM) rats. In DM rats, both acute and chronic therapy with the specific angiotensin II (ANG II) receptor antagonist losartan did not affect glomerular hyperfiltration or hyperperfusion but selectively normalized the glomerular capillary hydraulic pressure and ultrafiltration coefficient. To determine the basis of intrarenal hemodynamic responsiveness to RAS inhibition, we conducted biochemical, molecular biological, and immunohistochemical studies to assess endogenous RAS activity. Values for plasma renin concentration and serum angiotensin-converting enzyme (ACE) activity in DM rats were normal. In contrast, intrarenal renin protein content, and renin and angiotensinogen mRNAs, were increased in DM rats, suggesting disproportionate activation of the intrarenal RAS. Total renal ACE activity was significantly reduced in DM rats, but immunohistochemical studies indicated redistribution of ACE in the diabetic kidney. Proximal tubule ACE activity was reduced, but ACE immunostaining intensity was enhanced in glomeruli and renal vasculature. Together, these observations indicate increased RAS activity in those sites (glomeruli and vasculature) most likely to regulate hemodynamic function, potentially explaining the prominent responses to pharmacological blockade of ANG II formation and/or action.

Anti-Hypertensive Effect of Water Extract of Danshen on Renovascular Hypertension Through Inhibition of the Renin Angiotensin System

2002 ◽  
Vol 30 (01) ◽  
pp. 87-93 ◽  
Author(s):  
Dae Gill Kang ◽  
Yong Gab Yun ◽  
Jang Hyun Ryoo ◽  
Ho Sub Lee
Keyword(s):  
Plasma Concentration ◽  
Water Extract ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Dependent Manner ◽  
Converting Enzyme ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Ace Activity ◽  
Dose Dependent

A study was designed to elucidate the mechanism of anti-hypertensive effects of Danshen in the two-kidney, one clip (2K1C) Goldblatt renovascular hypertensive model, which is the renin-angiotensin system (RAS)-dependent hypertensive model. We investigated the effects of water extracts of Danshen on the angiotensin converting enzyme (ACE) activities, systolic blood pressure (SBP), and hormone levels in the plasma of 2K1C rats. ACE activity was inhibited by the addition of Danshen extract in a dose-dependent manner. SBP was decreased significantly after administration of Danshen extract in 2K1C, whereas plasma renin activity (PRA) was not changed. The plasma concentration of aldosterone (PAC) was decreased significantly in 2K1C group administered with Danshen extract, whereas the plasma concentration of ANP was increased by administration of Danshen extract for three weeks. These results suggest that Danshen has an anti-hypertensive effect through the inhibition of ACE, an essential regulatory enzyme of RAS.

Characterization of the renin-angiotensin system in the turtle Pseudemys scripta

1984 ◽  
Vol 247 (1) ◽  
pp. R15-R23 ◽  
Author(s):  
M. D. Cipolle ◽  
J. E. Zehr
Keyword(s):  
Pressor Response ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Ang Ii ◽  
Freshwater Turtles ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Fourfold Increase ◽  
Inactive Form ◽  
Pseudemys Scripta

Studies were conducted in freshwater turtles Pseudemys scripta to define some characteristics of the renin-angiotensin system in this reptile. Dialyzed acid-treated kidney extract (1 g tissue per ml water) produced a prolonged pressor response in unanesthetized turtles, which was eliminated by boiling the extract or by pretreating the turtle with [Sar1, Ile8]angiotensin II. A rat pressor assay was employed because turtle angiotensin (ANG) was bound poorly by the anti-[Asp1, Ile5, His9]ANG I used in our radioimmunoassay. Kidney extract incubated with homologous plasma (pH 5.5 and 25 degrees C) produced a time-dependent pressor response in rats. The pressor activity of the product was eliminated by dialysis or by pretreating the rats with [Sar1, Ile8]ANG II. The pressor response in anesthetized turtles to ANG I was significantly reduced by captopril, whereas the ANG II response remained unchanged, thus demonstrating the presence of ANG-converting enzyme activity in these animals. We determined the velocity of turtle ANG formation at various dilutions of enzyme (kidney extract) or substrate (plasma). Turtle kidney extract incubated with homologous plasma displayed typical Michaelis-Menten kinetics. Finally we conducted experiments to determine whether a portion of turtle plasma renin exists in an inactive form. Trypsinization caused a slight increase in plasma renin activity (PRA), whereas acidification to pH 3.3 yielded a fourfold increase in PRA.

Upregulation of renin-angiotensin system and downregulation of kallikrein in obstructive nephropathy

1993 ◽  
Vol 264 (5) ◽  
pp. F874-F881 ◽  
Author(s):  
S. S. el-Dahr ◽  
J. Gee ◽  
S. Dipp ◽  
B. G. Hanss ◽  
R. C. Vari ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Obstructive Nephropathy ◽  
Mrna Levels ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Kininase Ii ◽  
Plasma Angiotensin ◽  
Renin Mrna

The purpose of this study was to delineate the effects of prolonged (1 and 5 wk) unilateral ureteral obstruction (UUO) on the intrarenal renin-angiotensin and kallikrein-kinin systems in the rat. Systolic blood pressure (SBP) and plasma angiotensin (ANG) II levels were significantly higher at 1 and 5 wk of obstruction than in sham-operated groups. Also, plasma renin activity and ANG I levels were elevated at 1 wk (P < 0.05), and plasma angiotensin-converting enzyme (ACE)-kininase II activity was elevated at 5 wk (P < 0.05). Blockade of ANG II receptors with losartan (Dup 753) prevented the rise in SBP after UUO and normalized SBP in chronically hypertensive UUO rats. Renin mRNA levels and ANG II content were elevated in the obstructed kidneys at 1 and 5 wk compared with sham-operated kidneys (P < 0.05). ACE-kininase II activity was elevated in both the obstructed and contralateral kidneys at 5 wk compared with sham-operated kidneys (P < 0.05). In marked contrast to renin, total immunoreactive kallikrein contents and tissue kallikrein mRNA levels in the obstructed kidneys were reduced to 25% of sham-operated kidneys both at 1 and 5 wk (P < 0.001). The results indicate that urinary obstruction activates renin and suppresses kallikrein gene expression. Activation of ACE-kininase II by UUO also serves to enhance intrarenal ANG II generation and kinin degradation. The results implicate ANG II overproduction and kinin deficiency in the pathogenesis of UUO-induced hypertension and intrarenal vasoconstriction.

Low LBNP tolerance in men is associated with attenuated activation of the renin-angiotensin system

2000 ◽  
Vol 279 (3) ◽  
pp. R822-R829 ◽  
Author(s):  
John E. Greenleaf ◽  
Trine Welløw Petersen ◽  
Anders Gabrielsen ◽  
Bettina Pump ◽  
Peter Bie ◽  
...  
Keyword(s):  
Lower Body Negative Pressure ◽  
Venous Pressure ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
The Body ◽  
Ang Ii ◽  
Lower Body ◽  
Central Venous ◽  
Angiotensin System ◽  
Renin Angiotensin

Plasma vasoactive hormone concentrations [epinephrine (pEpi), norepinephrine (pNE), ANG II (pANG II), vasopressin (pVP), endothelin-1 (pET-1)] and plasma renin activity (pRA) were measured periodically and compared during lower body negative pressure (LBNP) to test the hypothesis that responsiveness of the renin-angiotensin system, the latter being one of the most powerful vasoconstrictors in the body, is of major importance for LBNP tolerance. Healthy men on a controlled diet (2,822 cal/day, 2 mmol · kg−1· day−1 Na+) were exposed to 30 min of LBNP from −15 to −50 mmHg. LBNP was uneventful for seven men [25 ± 2 yr, high-tolerance (HiTol) group], but eight men (26 ± 3 yr) reached presyncope after 11 ± 1 min [ P < 0.001, low-tolerance (LoTol) group]. Mean arterial pressure (MAP) did not change measurably, but central venous pressure and left atrial diameter decreased similarly in both groups (5–6 mmHg, by ≈30%, P < 0.05). Control (0 mmHg LBNP) hormone concentrations were similar between groups, however, pRAdiffered between them (LoTol 0.6 ± 0.1, HiTol 1.2 ± 0.1 ng ANG I · ml−1 · h−1, P < 0.05). LBNP increased ( P < 0.05) pRA and pANG II, respectively, more in the HiTol group (9.9 ± 2.2 ng ANG I · ml−1· h−1 and 58 ± 12 pg/ml) than in LoTol subjects (4.3 ± 0.9 ng ANG I · ml−1 · h−1 and 28 ± 6 pg/ml). In contrast, the increase in pVP was higher ( P < 0.05) in the LoTol than in the HiTol group. The increases ( P < 0.05) for pNE were nonsignificant between groups, and pET-1 remained unchanged. Thus there may be a causal relationship between attenuated activation of pRA and pANG II and presyncope, with pVP being a possible cofactor. Measurement of resting pRA may be of predictive value for those with lower hypotensive tolerance.

Characterization of renin-angiotensin system enzyme activities in cultured mouse podocytes

2007 ◽  
Vol 293 (1) ◽  
pp. F398-F407 ◽  
Author(s):  
Juan Carlos Q. Velez ◽  
Alison M. Bland ◽  
John M. Arthur ◽  
John R. Raymond ◽  
Michael G. Janech
Keyword(s):  
Mesangial Cells ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Glomerular Injury ◽  
Renin Substrate ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Neprilysin Inhibitor ◽  
Aminopeptidase A ◽  
Aminopeptidase A Inhibitor

Intraglomerular ANG II has been linked to glomerular injury. However, little is known about the contribution of podocytes (POD) to intraglomerular ANG II homeostasis. The aim of the present study was to examine the processing of angiotensin substrates by cultured POD. Our approach was to use matrix-assisted laser desorption/ionization time-of-flight (MALDI-TOF) mass spectrometry for peptide determination from conditioned cell media and customized AQUA peptides for quantification. Immortalized mouse POD were incubated with 1-2 μM ANG I, ANG II, or the renin substrate ANG-(1-14) for different time intervals and coincubated in parallel with various inhibitors. Human mesangial cells (MES) were used as controls. POD incubated with 1 μM ANG I primarily formed ANG-(1-9) and ANG-(1-7). In contrast, MES incubated with ANG I primarily generated ANG II. In POD, ANG-(1-7) was the predominant product, and its formation was inhibited by a neprilysin inhibitor. Modest angiotensin-converting enzyme (ACE) activity was also detected in POD, although only after cells were incubated with 2 μM ANG I. In addition, we observed that POD degraded ANG II into ANG III and ANG-(1-7). An aminopeptidase A inhibitor inhibited ANG III formation, and an ACE2 inhibitor led to ANG II accumulation. Furthermore, we found that POD converted ANG-(1-14) to ANG I and ANG-(1-7). This conversion was inhibited by a renin inhibitor. These findings demonstrate that POD express a functional intrinsic renin-angiotensin system characterized by neprilysin, aminopeptidase A, ACE2, and renin activities, which predominantly lead to ANG-(1-7) and ANG-(1-9) formation, as well as ANG II degradation. These findings may reflect a specific role of POD in maintenance of intraglomerular renin-angiotensin system balance.

Isoproterenol-induced cardiac hypertrophy: role of circulatory versus cardiac renin-angiotensin system

2001 ◽  
Vol 281 (6) ◽  
pp. H2410-H2416 ◽  
Author(s):  
Frans H. H. Leenen ◽  
Roselyn White ◽  
Baoxue Yuan
Keyword(s):  
Cardiac Hypertrophy ◽  
Enzyme Inhibitor ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Left Ventricular ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Male Wistar Rats ◽  
Β Receptor

To assess the possible contribution of the circulatory and cardiac renin-angiotensin system (RAS) to the cardiac hypertrophy induced by a β-agonist, the present study evaluated the effects of isoproterenol, alone or combined with an angiotensin I-converting enzyme inhibitor or AT1 receptor blocker, on plasma and LV renin activity, ANG I, and ANG II, as well as left ventricular (LV) and right ventricular (RV) weight. Male Wistar rats received isoproterenol by osmotic minipump subcutaneously and quinapril or losartan once daily by gavage. Plasma and LV ANGs were measured by radioimmunoassay after separation by HPLC. Isoproterenol alone decreased blood pressure, more markedly when combined with losartan or quinapril. Isoproterenol significantly increased LV and RV weight and total collagen. Neither losartan nor quinapril inhibited the increases in LV or RV weight. Losartan prevented the increase in RV collagen but enhanced the increase in LV collagen. Isoproterenol increased plasma renin, ANG I, and ANG II three- to fourfold. Isoproterenol combined with losartan or quinapril, caused marked further increases except for a significant decrease in plasma ANG II with quinapril. Isoproterenol alone did not increase LV ANG II and, combined with losartan or quinapril, actually decreased LV ANG II. These results indicate that isoproterenol-induced cardiac hypertrophy is associated with clear increases in plasma ANG II, but not in LV ANG II. Both losartan and quinapril lower LV ANG II below control levels, but do not prevent the isoproterenol-induced cardiac hypertrophy. These findings do not support a role for the circulatory or cardiac RAS in the cardiac trophic responses to β-receptor stimulation.

scholarly journals Renin knockout rat: control of adrenal aldosterone and corticosterone synthesis in vitro and adrenal gene expression

2015 ◽  
Vol 308 (1) ◽  
pp. R73-R77 ◽  
Author(s):  
Hershel Raff ◽  
Ashley Gehrand ◽  
Eric D. Bruder ◽  
Matthew J. Hoffman ◽  
William C. Engeland ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Immunohistochemical Analysis ◽  
Zona Glomerulosa ◽  
Ang Ii ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Aldosterone Production ◽  
Renin Mrna

The classic renin-angiotensin system is partly responsible for controlling aldosterone secretion from the adrenal cortex via the peptide angiotensin II (ANG II). In addition, there is a local adrenocortical renin-angiotensin system that may be involved in the control of aldosterone synthesis in the zona glomerulosa (ZG). To characterize the long-term control of adrenal steroidogenesis, we utilized adrenal glands from renin knockout (KO) rats and compared steroidogenesis in vitro and steroidogenic enzyme expression to wild-type (WT) controls (Dahl S rat). Adrenal capsules (ZG; aldosterone production) and subcapsules [zona reticularis/fasciculata (ZFR); corticosterone production] were separately dispersed and studied in vitro. Plasma renin activity and ANG II concentrations were extremely low in the KO rats. Basal and cAMP-stimulated aldosterone production was significantly reduced in renin KO ZG cells, whereas corticosterone production was not different between WT and KO ZFR cells. As expected, adrenal renin mRNA expression was lower in the renin KO compared with the WT rat. Real-time PCR and immunohistochemical analysis showed a significant decrease in P450aldo ( Cyp11b2) mRNA and protein expression in the ZG from the renin KO rat. The reduction in aldosterone synthesis in the ZG of the renin KO adrenal seems to be accounted for by a specific decrease in P450aldo and may be due to the absence of chronic stimulation of the ZG by circulating ANG II or to a reduction in locally released ANG II within the adrenal gland.

The effect of hypothalamo-pituitary disconnection on the renin-angiotensin system in the late-gestation fetal sheep

2005 ◽  
Vol 288 (5) ◽  
pp. R1279-R1287 ◽  
Author(s):  
Kai Chen ◽  
Luke C. Carey ◽  
Jingfang Liu ◽  
Nancy K. Valego ◽  
Stephen B. Tatter ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Fetal Tissue ◽  
Late Gestation ◽  
Receptor Subtype ◽  
Postnatal Life ◽  
Ang Ii ◽  
Fetal Sheep ◽  
Angiotensin System ◽  
Renin Angiotensin

The activity of the renin-angiotensin system (RAS) increases significantly in the late-gestation fetal sheep. Fetal cortisol is also increased during this time, and it is thought that the increase in cortisol may modulate the RAS changes. Previous studies have examined the effects of cortisol infusion on RAS activity, but the effects of blocking the peripartum increase in cortisol concentrations on the developmental changes in the RAS are not known. Therefore, we utilized the technique of hypothalamic-pituitary disconnection (HPD), which prevents the cortisol surge from occurring, to investigate the importance of the late-gestation increase in cortisol on the ontogenic changes in RAS activity. HPD of fetal sheep was performed at 120 days of gestational age (dGA), and fetuses were delivered between 135 and 139 dGA. Control fetuses were sham operated. HPD blocked the late-gestation cortisol increase but did not alter renal renin mRNA, renal renin or prorenin protein content, nor plasma renin levels compared with sham operated. However, HPD fetuses had increased ANG II receptor subtype 1 (AT1) mRNA and protein expression in the kidney and lungs. ANG II receptor subtype 2 (AT2) expression was not altered in these tissues at either mRNA or protein level. HPD did not change AT1 or AT2 mRNA in the left ventricle but did result in decreased protein levels for both receptors. These studies demonstrate that blockade of the naturally occurring increase in fetal cortisol concentration in late gestation is associated with tissue-specific alterations in expression of AT1 and AT2 receptors. These changes may impact on fetal tissue maturation and hence have consequences in postnatal life.

Vasoactive intestinal peptide down-regulates the intrahepatic renin–angiotensin system in the anaesthetized rat

2000 ◽  
Vol 99 (3) ◽  
pp. 201-206
Author(s):  
V. Z. C. YE ◽  
K. A. DUGGAN
Keyword(s):  
Angiotensin Ii ◽  
Vasoactive Intestinal Peptide ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Sprague Dawley ◽  
Angiotensin I ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Sodium Loading ◽  
Ace Activity

Gastric sodium loading results in an increase in the portal venous concentration of vasoactive intestinal peptide (VIP) and down-regulation of both the intrahepatic and circulating renin–angiotensin systems. In the present study we sought to determine whether an increase in the concentration of VIP in the portal circulation might act to down-regulate the intrahepatic and/or circulating renin–angiotensin systems. Male Sprague–Dawley rats were infused intraportally with haemaccel vehicle or VIP in haemaccel for 60 min. Livers were harvested and blood was sampled. Angiotensin-converting enzyme (ACE) activity and angiotensinogen, angiotensin I, angiotensin II and renin concentrations were measured. VIP infusion decreased hepatic ACE activity (P < 0.05), the hepatic angiotensinogen concentration (P < 0.001) and the hepatic angiotensin I concentration (P < 0.05). The plasma angiotensinogen concentration and serum ACE activity were also decreased by intraportal VIP infusion (P < 0.05 for each). Plasma renin, angiotensin I and angiotensin II concentrations were unchanged by VIP infusion. We conclude that an increase in the portal venous VIP concentration down-regulates the intrahepatic renin–angiotensin system. These changes are similar to those reported after gastric sodium loading, and we suggest, therefore, that the increase in portal venous VIP that occurs after gastric sodium is the means by which the gastric sodium sensor signals the liver to effect these changes in the renin–angiotensin system.

The Renin Angiotensin System and Bipolar Disorder: A Systematic Review

2020 ◽  
Vol 27 (6) ◽  
pp. 520-528 ◽  
Author(s):  
Izabela Guimarães Barbosa ◽  
Giulia Campos Ferreira ◽  
Diomildo Ferreira Andrade Júnior ◽  
Cássio Rocha Januário ◽  
André Rolim Belisário ◽  
...  
Keyword(s):  
Systematic Review ◽  
Bipolar Disorder ◽  
Cardiovascular Diseases ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin Receptors ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Search Terms

Bipolar Disorder (BD) is a chronic a multifactorial psychiatric illness that affects mood, cognition, and functioning. BD is associated with several psychiatric conditions as well clinical comorbidities, particularly cardiovascular diseases. The neurobiology of BD is complex and multifactorial and several systems have been implicated. Considering that the Renin Angiotensin System (RAS) plays an important role in cardiovascular diseases and that recently evidence has suggested its role in psychiatric disorders, the aim of the present study is to summarize and to discuss recent findings related to the modulation of RAS components in BD. A systematic search of the literature using the electronic databases MEDLINE and LILACS was conducted through March 2019. The search terms were: “Bipolar Disorder”; “Renin Angiotensin System”; “Angiotensin 2”; “Angiotensin receptors”; “Angiotensin 1-7”; “ACE”; “ACE2”; “Mas Receptor”. We included original studies assessing RAS in BD patients. Two hundred twenty-two citations were initially retrieved. Eleven studies were included in our systematic review. In the majority of studies (6 of 8), the ACE insertion/deletion (I/D) polymorphism did not differ between BD patients and controls. BD patients presented higher plasma renin activity in comparison with controls. The studies evaluating the RAS molecules in BD are very scarce and heterogeneous. The literature suggests a potential role of RAS in BD. Further studies are necessary to investigate this relationship.

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