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.

Localization of components of the renin–angiotensin system in the suprachiasmatic nucleus of normotensive Sprague–Dawley rats

2004 ◽  
Vol 1008 (2) ◽  
pp. 212-223 ◽  
Author(s):  
Martin Alexander Thomas ◽  
Gerta Fleissner ◽  
Marion Stöhr ◽  
Stefan Hauptfleisch ◽  
Björn Lemmer
Keyword(s):  
Suprachiasmatic Nucleus ◽  
Renin Angiotensin System ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Sprague Dawley Rats

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.

Modulation of the intrahepatic renin–angiotensin system after stimulation of the gastric sodium monitor in the rat

1999 ◽  
Vol 98 (1) ◽  
pp. 57-64
Author(s):  
V. Z. C. YE ◽  
K. A. DUGGAN
Keyword(s):  
Renin Angiotensin System ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Angiotensin System ◽  
Low Sodium Diet ◽  
Low Sodium ◽  
Sprague Dawley Rats ◽  
Sodium Load ◽  
Ace Activity ◽  
Stimulation Of

Changes in the rate of formation of angiotensin II (ANG II) participate in mediating the natriuresis that occurs in direct response to a gastric sodium stimulus (upper-gut sodium monitor). As this natriuresis is also dependent on intrahepatic events, we investigated whether changes in hepatic and plasma angiotensinogen levels and hepatic angiotensin-converting enzyme (ACE) activity might explain the decrease in ANG II synthesis. Male Sprague–Dawley rats, equilibrated on a low-sodium diet, were anaesthetized and received a sodium load of 1.5 mmol/kg (using 3× normal saline) either intragastrically or intravenously. Blood and livers were sampled before and at various times after sodium administration. ACE activity in serum and tissues was determined by generation of histidyl-leucine. Angiotensinogen was determined by radioimmunoassay of angiotensin I generated by incubation in the presence of exogenous renin. Plasma angiotensinogen had decreased significantly by 15 min after sodium administration (P< 0.005), while hepatic angiotensinogen was also decreased significantly from 30 min after the sodium load (P< 0.01). Hepatic ACE activity decreased in response to sodium (P< 0.005) from 30 min. We conclude that stimulation of the gastric sodium monitor regulates angiotensinogen synthesis and secretion by the liver, as well as hepatic ACE activity.

Role of tissue renin angiotensin system in two-kidney, one-clip hypertensive rats

1993 ◽  
Vol 264 (3) ◽  
pp. F510-F514
Author(s):  
R. Morishita ◽  
J. Higaki ◽  
H. Okunishi ◽  
F. Nakamura ◽  
M. Nagano ◽  
...  
Keyword(s):  
Mrna Level ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Ang Ii ◽  
Gene Expressions ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Significant Difference ◽  
Renin Mrna ◽  
The Brain

To investigate the molecular pathology of two-kidney, one-clip (2K-1C) rats, we examined the gene expressions of the renin-angiotensin system (RAS) and angiotensin II (ANG II) concentration in various tissues in the early (4 wk) and chronic (16 wk) phases of hypertension. Four weeks after clipping, the brain renin mRNA level was lower in 2K-1C rats than in control rats (P < 0.05). On the other hand, the levels of brain and renal angiotensinogen mRNA were not significantly different in the two groups. The brain and adrenal ANG II concentrations were significantly higher in 2K-1C rats than in control rats. Sixteen weeks after clipping, there was no significant difference in the brain renin mRNA levels in the two groups, and renal and brain angiotensinogen mRNA levels were normal. Moreover, the ANG II concentrations in the adrenals and brain (except the cortex) of 2K-1C rats were not significantly higher than those in control rats. These results show a differential pattern of tissue RAS gene expression in rats during the development of 2K-1C hypertension, which is regulated in a tissue-specific manner. Furthermore, the data suggest that brain ANG II may be affected by circulating ANG II, but not by the brain renin angiotensin system, and may regulate brain renin, probably by negative feedback through its own receptor.

scholarly journals Alterations of the renin-angiotensin system at the RVLM of transgenic rats with low brain angiotensinogen

2001 ◽  
Vol 280 (2) ◽  
pp. R428-R433 ◽  
Author(s):  
Ovidiu Baltatu ◽  
Marco A. P. Fontes ◽  
Maria J. Campagnole-Santos ◽  
Sordaine Caligiorni ◽  
Detlev Ganten ◽  
...  
Keyword(s):  
Renin Angiotensin System ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Transgenic Rats ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
The Mean ◽  
Low Levels

The transgenic rats TGR(ASrAOGEN) (TGR) with low levels of brain angiotensinogen were analyzed for cardiovascular reactivity to microinjections of ANG II and angiotensin receptor (AT1) antagonists [CV-11974, AT1 specific; A-779, ANG-(1–7) selective; sarthran, nonspecific] into the rostral ventrolateral medulla (RVLM) of conscious rats. Microinjection of ANG II resulted in a significantly higher increase in the mean arterial pressure (MAP) of TGR than control [Sprague-Dawley (SD)] rats, suggesting an upregulation of ANG II receptors in TGR. CV-11974 produced an increase in MAP of SD but not in TGR rats. A-779 produced a depressor response in SD but not in TGR rats. Conversely, sarthran produced a similar decrease of MAP in both rat groups. The pressor effect of the AT1 antagonist may indicate an inhibitory role of AT1 receptors in the RVLM. On the other hand, ANG-(1–7) appears to have a tonic excitatory role in this region. The altered response to specific angiotensin antagonists in TGR further supports the functionally relevant decrease in angiotensins in the brains of TGR and corroborates the importance of the central renin-angiotensin system in cardiovascular homeostasis.

Novel expression and regulation of the renin-angiotensin system in metanephric organ culture

2000 ◽  
Vol 279 (2) ◽  
pp. R522-R530 ◽  
Author(s):  
Victoria F. Norwood ◽  
Marjorie Garmey ◽  
Jeffrey Wolford ◽  
Robert M. Carey ◽  
R. Ariel Gomez
Keyword(s):  
Organ Culture ◽  
Renin Angiotensin System ◽  
Feedback Mechanism ◽  
Renin Activity ◽  
Ang Ii ◽  
Isolated Cells ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Renin Mrna ◽  
Positive Feedback Mechanism

To evaluate the presence and regulation of the renin-angiotensin system (RAS) in metanephric organ culture, embryonic day 14 (E14) rat metanephroi were cultured for 6 days. mRNAs for renin and both ANG II receptors (AT1 and AT2) are expressed at E14, and all three genes continue to be expressed in culture. Renin mRNA is localized to developing tubules and ureteral branches in the cultured explants. At E14, renin immunostaining is found in isolated cells scattered within the mesenchyme. As differentiation progresses, renin localizes to the ureteric epithelium, developing tubules and glomeruli. E14 metanephroi contain ANG II, and peptide production persists in culture. Renin activity is present at E14 (6.13 ± 0.61 pg ANG I · kidney−1 · h−1) and in cultured explants (28.84 ± 1.13 pg ANG I · kidney−1 · h−1). Renin activity in explants is increased by ANG II treatment (70.1 ± 6.36 vs. 40.97 ± 1.94 pg ANG I · kidney−1 · h−1 in control). This increase is prevented by AT1 blockade, whereas AT2 antagonism has no effect. These studies document an operational local RAS and a previously undescribed positive-feedback mechanism for renin generation in avascular, cultured developing metanephroi. This novel expression pattern and regulatory mechanism highlight the unique ability of developing renal cells to express an active RAS.

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