In situ localization of renin and its mRNA in neonatal ureteral obstruction

1990 ◽  
Vol 258 (4) ◽  
pp. F854-F862 ◽  
Author(s):  
S. S. el-Dahr ◽  
R. A. Gomez ◽  
M. S. Gray ◽  
M. J. Peach ◽  
R. M. Carey ◽  
...  
Keyword(s):  
Ureteral Obstruction ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Renin Angiotensin ◽  
Renal Vasoconstriction ◽  
Renin Mrna ◽  
Renin Content

Angiotensin II is an important mediator of renal vasoconstriction resulting from chronic unilateral ureteral obstruction (UUO). Distribution of renin mRNA and immunoreactive renin (IR) was examined in kidneys of 1-mo-old Sprague-Dawley rats subjected to either sham operation (n = 21), left complete UUO (n = 21), or right uninephrectomy (UNX, n = 16) at 2 days of age. There were no differences among the three groups in mean arterial pressure or plasma renin activity. Unlike sham kidneys, in which IR was detected in less than 55% of juxtaglomerular apparatuses (JGA) and was confined to a juxtaglomerular location, IR in both kidneys of animals with UUO appeared in greater than 75% of JGA and extended along most of the length of the afferent arteriole (P less than 0.01). In contrast, IR in kidneys of UNX rats was localized to the JGA as in sham-operated animals. Compared with sham-operated kidneys, renal renin content was increased in the obstructed kidneys (P less than 0.01) but decreased in the intact opposite kidneys of UUO rats and in the remaining kidneys of UNX rats (P less than 0.05). Renin mRNA, detected by in situ hybridization histochemistry, was localized to the JGA in kidneys of all groups. However, the fraction of JGA containing detectable renin mRNA was higher in obstructed kidneys than in intact opposite, UNX, or sham kidneys (P less than 0.05). In conclusion, UUO alters intrarenal renin independent of the systemic renin-angiotensin system. The greater distribution of IR, increased renin content, and renin gene expression of kidneys with ipsilateral UUO are consistent with a role for renin-angiotensin in mediating the vasoconstriction resulting from UUO.

Regulation of angiotensin II AT1 and AT2 receptors in neonatal ureteral obstruction

1997 ◽  
Vol 273 (2) ◽  
pp. R503-R509 ◽  
Author(s):  
K. H. Yoo ◽  
V. F. Norwood ◽  
S. S. el-Dahr ◽  
I. Yosipiv ◽  
R. L. Chevalier
Keyword(s):  
Angiotensin Ii ◽  
Receptor Binding ◽  
Ureteral Obstruction ◽  
Interstitial Fibrosis ◽  
Renin Angiotensin System ◽  
Sham Operation ◽  
At2 Receptor ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Renal Vasoconstriction

Chronic unilateral ureteral obstruction (UUO) in early development activates the intrarenal renin-angiotensin system and leads to profound renal vasoconstriction, renal growth arrest, and interstitial fibrosis. To investigate the response of the AT1 and AT2 subtypes of the angiotensin II (ANG II) receptors to UUO, Sprague-Dawley rats underwent UUO or control sham operation in the first 48 h of life and were studied 1-28 days later. Renal mRNA for renin, AT1 and AT2 receptor, and receptor binding and distribution were determined. In contrast to controls, renin mRNA increased from 14 to 28 days in the obstructed kidney. After ipsilateral UUO, AT1 mRNA was suppressed at 1 day, but had increased compared with controls at 28 days. AT2 receptor mRNA fell rapidly in all kidneys from 1 to 3 days of age, after which it remained undetectable. Compared with the intact opposite kidney, AT2 mRNA was suppressed in the obstructed kidney 1 day after UUO. Compared with controls, AT1 and AT2 receptor binding was decreased by ipsilateral UUO at 1 day, whereas AT1 binding was increased at 28 days. Renal ANG II content was increased in the obstructed compared with the intact opposite kidney 28 days after UUO. In view of the increase in renal renin and angiotensin II production resulting from UUO, increased renal AT1 mRNA and receptor binding are likely to contribute to the vasoconstriction and interstitial fibrosis of the neonatal kidney after prolonged UUO.

What Stimulates the Renin—Angiotensin System in Rats with two-Kidney Renal Hypertension?

1983 ◽  
Vol 64 (5) ◽  
pp. 463-470
Author(s):  
Y. Takata ◽  
A. E. Doyle ◽  
M. Veroni ◽  
S. G. Duffy
Keyword(s):  
Blood Pressure ◽  
Plasma Renin Activity ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Renin Activity ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Contralateral Kidney ◽  
The One ◽  
Renin Content

1. Blood pressure, the hypotensive effect of captopril, plasma renin activity, renal renin content and kidney weight were measured in the two-kidney—one-clip model, the one-kidney—one-clip model and the two-kidney—one-clip model with the ureter of the contralateral kidney ligated in rats. The ureteric ligation was performed to abolish urinary excretion from the contralateral kidney in the two-kidney—one-clip model. 2. The development of hypertension after renal artery constriction was earlier and greater in the one-kidney—one-clip model and the two-kidney—one-clip model with ureter of the contralateral kidney ligated than in the two-kidney—one-clip model. A single oral dose of captopril produced a greater fall in blood pressure in both the two-kidney models than in the one-kidney—one-clip group. 3. Plasma renin activity and renal renin content of the clipped kidney were higher in the two-kidney model rats, whether or not the ureter had been ligated, than in the one-kidney—one-clip model animals, although more than half the rats from the two-kidney model had normal values. There was a significant correlation between plasma renin activity and the response to captopril in all groups, whereas in none of the three groups was the correlation between plasma renin activity and blood pressure significant. 4. The clipped kidney had a higher renin content than did the contralateral kidney, and the weight of the ischaemic kidney was decreased compared with the contralateral kidney whether it was untouched or had its ureter ligated. The weight of the clipped kidney was in the order one-kidney—one-clip model > two-kidney—one-clip model with ureter of the contralateral kidney ligated > two-kidney—one-clip model. 5. It was concluded that the renin-angiotensin system was stimulated to the similar degree in some animals for the two-kidney—one-clip models, whether or not the ureter of the contralateral kidney had been ligated, compared with the one-kidney—one-clip animals. This finding suggests that the contralateral kidney can stimulate renin secretion and synthesis in the clipped kidney independently of Na+ excretion.

Peripheral and central angiotensin II regulates expression of genes of the renin-angiotensin system

1992 ◽  
Vol 262 (5) ◽  
pp. E651-E657 ◽  
Author(s):  
K. Kohara ◽  
K. B. Brosnihan ◽  
C. M. Ferrario ◽  
A. Milsted
Keyword(s):  
Northern Blot Analysis ◽  
Renin Angiotensin System ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Expression Of Genes ◽  
Sprague Dawley Rats ◽  
Renin Mrna ◽  
Lower Brain Stem

We investigated whether angiotensin (ANG) II has the potential to regulate expression of genes of the renin-angiotensin system (RAS) in peripheral and central tissues. ANG II (0.1 or 6.0 nmol/h) was infused by osmotic minipump into male Sprague-Dawley rats (225-250 g) for 5 days, either intravenously or intracerebroventricularly. We measured angiotensinogen mRNA in liver, adrenal glands, and brain (hypothalamus and lower brain stem), renin mRNA in the kidney, and angiotensin-converting enzyme (ACE) mRNA in the lung and testis by Northern blot analysis. We demonstrated that plasma ANG II increases the levels of liver angiotensinogen mRNA, decreases kidney renin mRNA, and decreases lung ACE mRNA. Intracerebroventricular administration of ANG II resulted in a different pattern of responses of the peripheral RAS components. Liver angiotensinogen mRNA was increased, and kidney renin mRNA was decreased by both doses of ANG II, whereas lung ACE mRNA remained unresponsive at either dose. Centrally mediated influences of ANG II are most likely indirect since plasma ANG II concentration was not changed. This study has revealed that ANG II has profound diverse effects that influence the regulation of its formation. Further, results indicate that genes of the RAS responded to exogenous ANG II in both tissue- and route-specific ways.

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.

scholarly journals Local renin-angiotensin system contributes to hyperthyroidism-induced cardiac hypertrophy

1999 ◽  
Vol 160 (1) ◽  
pp. 43-47 ◽  
Author(s):  
H Kobori ◽  
A Ichihara ◽  
Y Miyashita ◽  
M Hayashi ◽  
T Saruta
Keyword(s):  
Angiotensin Ii ◽  
Thyroid Hormone ◽  
Cardiac Hypertrophy ◽  
Plasma Renin Activity ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Plasma Angiotensin ◽  
Renin Mrna

We have reported previously that thyroid hormone activates the circulating and tissue renin-angiotensin systems without involving the sympathetic nervous system, which contributes to cardiac hypertrophy in hyperthyroidism. This study examined whether the circulating or tissue renin-angiotensin system plays the principal role in hyperthyroidism-induced cardiac hypertrophy. The circulating renin-angiotensin system in Sprague-Dawley rats was fixed by chronic angiotensin II infusion (40 ng/min, 28 days) via mini-osmotic pumps. Daily i.p. injection of thyroxine (0.1 mg/kg per day, 28 days) was used to mimic hyperthyroidism. Serum free tri-iodothyronine, plasma renin activity, plasma angiotensin II, cardiac renin and cardiac angiotensin II were measured with RIAs. The cardiac expression of renin mRNA was evaluated by semiquantitative reverse transcriptase-polymerase chain reaction. Plasma renin activity and plasma angiotensin II were kept constant in the angiotensin II and angiotensin II+thyroxine groups (0.12+/-0.03 and 0.15+/-0.03 microgram/h per liter, 126+/-5 and 130+/-5 ng/l respectively) (means+/-s.e.m.). Despite stabilization of the circulating renin-angiotensin system, thyroid hormone induced cardiac hypertrophy (5.0+/-0.5 vs 3.5+/-0.1 mg/g) in conjunction with the increases in cardiac expression of renin mRNA, cardiac renin and cardiac angiotensin II (74+/-2 vs 48+/-2%, 6.5+/-0.8 vs 3.8+/-0.4 ng/h per g, 231+/-30 vs 149+/-2 pg/g respectively). These results indicate that the local renin-angiotensin system plays the primary role in the development of hyperthyroidism-induced cardiac hypertrophy.

The Renin-Angiotensin System in Acute Renal Failure of Rats

1975 ◽  
Vol 48 (6) ◽  
pp. 467-473 ◽  
Author(s):  
W. Rauh ◽  
P. Oster ◽  
R. Dietz ◽  
F. Gross
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Angiotensin Ii ◽  
Passive Immunization ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Glycerol Injection ◽  
Renin Content

1. Acute renal failure was produced in rats by intramuscular injection of glycerol. Subsequently, changes in the concentrations of renin and of angiotensin II in plasma and the renin content of the kidneys were followed. 2. At 4 and 8 h after glycerol administration, plasma renin and angiotensin II had increased two-to three-fold; they remained elevated for 48 h and then returned towards normal. At 7 days, the values were still slightly raised. 3. At 4 and 8 h after glycerol injection, kidney renin had decreased but it had increased after 24 and 48 h. 4. Passive immunization with angiotensin II antibodies, given at the time of glycerol injection and 2 and 4 h afterwards, prevented the development of acute renal failure. When angiotensin II antiserum was administered later (8, 10 and 12 h after glycerol) it had no effect. 5. Stimulation of the renin-angiotensin system may be involved in the pathogenesis of the early phase of acute renal failure.

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.

Distribution and content of renin and renin mRNA in remnant kidney of adult rat

1992 ◽  
Vol 263 (4) ◽  
pp. F731-F738 ◽  
Author(s):  
C. Pupilli ◽  
R. L. Chevalier ◽  
R. M. Carey ◽  
R. A. Gomez
Keyword(s):  
Left Kidney ◽  
Weight Ratio ◽  
Plasma Renin ◽  
Sham Operation ◽  
Sprague Dawley ◽  
Dot Blot ◽  
Adult Rat ◽  
Sprague Dawley Rats ◽  
Renin Mrna ◽  
Dot Blot Assay

To determine whether kidney hypertrophy secondary to reduction of renal mass affects the intrarenal distribution and concentration of renin mRNA and its protein, adult male Sprague-Dawley rats were studied 4 wk after sham operation (Sham, n = 10), uninephrectomy (UNX, n = 14), or five-sixths nephrectomy (5/6 NX, n = 12). Left kidney weight-to-body weight ratio (x10(3)) was higher in 5/6 NX (6.6 +/- 0.2) than in UNX (4.5 +/- 0.2) or Sham (3.8 +/- 0.1) groups (P < 0.001). The percentage of juxtaglomerular apparatuses (%JGA) containing renin was lower in 5/6 NX (32 +/- 5) than in UNX (56 +/- 2, P < 0.001) or Sham (50 +/- 1, P < 0.05) groups. Renal renin mRNA concentrations (pg renin mRNA/microgram total RNA) detected by radiodensitometric renin mRNA dot-blot assay were lower in 5/6 NX (1.8 +/- 0.3) than in UNX (13.2 +/- 1) or Sham (14.2 +/- 1.1, P < 0.001). In situ hybridization histochemistry demonstrated that in all groups of rats renin mRNA was confined to the JGA. However, the hybridization signals (grains/JGA) were less intense in 5/6 NX (211 +/- 24) than in UNX (486 +/- 35) or Sham (541 +/- 40) groups (P < 0.001). Renal renin concentration (ng angiotensin I.mg protein-1.h-1) tended to be lower in 5/6 NX (20 +/- 15) than in UNX (44 +/- 7.8) or Sham (60.8 +/- 10) groups. In addition, plasma renin activity (ng.ml-1.h-1) was lower in 5/6 NX (3.8 +/- 0.6) than in UNX (8.8 +/- 1.8, P < 0.05) or Sham (14.3 +/- 2, P < 0.001) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

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.

Renal vascular response to heat stress in baboons--role of renin-angiotensin

1977 ◽  
Vol 43 (4) ◽  
pp. 739-746 ◽  
Author(s):  
M. M. Eisman ◽  
L. B. Rowell
Keyword(s):  
Angiotensin Ii ◽  
Renin Angiotensin System ◽  
Plasma Renin ◽  
Papio Cynocephalus ◽  
Renin Angiotensin ◽  
Renal Vasoconstriction ◽  
Ambient Temperatures ◽  
Angiotensin Ii Antagonist ◽  
Renal Vascular

To determine if hyperthermia in the baboon caused a reduction of renal blood flow (RBF) similar to that reported in man, we repeatedly exposed six unanesthetized male baboons (Papio cynocephalus) to ambient temperatures of 42.5–49.0 degrees C for 55–175 min. Internal temperatures rose 1.0–2.0 degrees C. On the average, RBF fell 23.7% per degrees C, renal vascular resistance (RVR) rose 34.0% per degrees C, and mean arterial pressure (MAP) fell by only 2.9 Torr. Plasma renin activity (PRA), measured in four baboons, rose 97.5% per degrees C. To investigate the role of the renin-angiotensin system in this renal response, we infused propranolol or saralasin (1-sar-8-ala-angiotensin II), an angiotensin II antagonist, systemically in 14 experiments on three baboons. Both propranolol and saralasin infusions prevented most of the reduction in RBF during hyperthermia. Propranolol prevented the increase in PRA. We conclude that renal vasoconstriction accompanies moderate hyperthermia in the awake baboon, and much of this response is mediated by a beta-adrenergic release of renin.

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