A Widespread Abnormality of Renin Gene Expression in the Spontaneously Hypertensive Rat: Modulation in Some Tissues with the Development of Hypertension

1989 ◽  
Vol 77 (6) ◽  
pp. 629-636 ◽  
Author(s):  
Nilesh J. Samani ◽  
John D. Swales ◽  
William J. Brammar
Keyword(s):  
Gene Expression ◽  
Messenger Rna ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Angiotensin System ◽  
Spontaneously Hypertensive ◽  
Renin Angiotensin ◽  
Renin Gene ◽  
Renin Mrna ◽  
Ribonuclease Protection

1. Renin messenger RNA (mRNA) levels were compared in the kidneys, livers, brains, adrenals, aortae and hearts of spontaneously hypertensive (SHR) and Wistar—Kyoto (WKY) rats at 5 and 12 weeks of age using a ribonuclease-protection technique 2. Relative levels of renin mRNA were increased in the kidney, liver, brain, adrenal and heart of the young SHR compared with the WKY. In the aorta, levels were similar in the two strains at 5 weeks 3. In 12-week-old animals, while increased levels persisted in the liver, brain and adrenal of the SHR, the level in the kidney was now the same in the two strains and the levels in the heart and aorta were lower in the SHR compared with the WKY 4. Renin mRNA levels in the kidneys of SHR and WKY were also compared by Northern blotting and confirmed the observations made with the ribonuclease-protection technique 5. The findings indicate a widespread abnormality of renin gene expression in the SHR which is modulated in some tissues by the development of hypertension 6. While the mechanism(s) for the abnormality remains to be determined, the increased renin mRNA levels in the SHR in several tissues concerned with blood pressure regulation suggests an important role for the renin-angiotensin system in the development and maintenance of hypertension 7. However, the finding of increased renin mRNA in the liver also suggests abnormalities in other, as yet unknown, functions of the renin—angiotensin system in the SHR.

scholarly journals Expression of the renin gene in extra-renal tissues of the rat

1988 ◽  
Vol 253 (3) ◽  
pp. 907-910 ◽  
Author(s):  
N J Samani ◽  
J D Swales ◽  
W J Brammar
Keyword(s):  
Renin Angiotensin System ◽  
Regulatory Role ◽  
Mrna Levels ◽  
Dietary Salt ◽  
Angiotensin System ◽  
Rat Organs ◽  
Renin Gene ◽  
Renin Mrna ◽  
Ribonuclease Protection ◽  
The Brain

Expression of the renin gene in several rat organs is demonstrated by the detection of renin mRNA using a ribonuclease-protection technique. In two of these sites, the brain and the liver, renin mRNA levels are unaffected by changes in dietary salt which markedly affect renal renin mRNA levels. The findings provide the basis for an important ubiquitous local regulatory role for the renin-angiotensin system extending beyond the circulation.

Regulation of nonclassical renin-angiotensin system receptor gene expression in the adrenal medulla by acute and repeated immobilization stress

2015 ◽  
Vol 308 (6) ◽  
pp. R517-R529 ◽  
Author(s):  
Regina Nostramo ◽  
Lidia Serova ◽  
Marcela Laukova ◽  
Andrej Tillinger ◽  
Chandana Peddu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adrenal Medulla ◽  
Immobilization Stress ◽  
Receptor Gene ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Catecholamine Biosynthesis ◽  
Receptor Mrna

The involvement of the nonclassical renin-angiotensin system (RAS) in the adrenomedullary response to stress is unclear. Therefore, we examined basal and immobilization stress (IMO)-triggered changes in gene expression of the classical and nonclassical RAS receptors in the rat adrenal medulla, specifically the angiotensin II type 2 (AT2) and type 4 (AT4) receptors, (pro)renin receptor [(P)RR], and Mas receptor (MasR). All RAS receptors were identified, with AT2 receptor mRNA levels being the most abundant, followed by the (P)RR, AT1A receptor, AT4 receptor, and MasR. Following a single IMO, AT2 and AT4 receptor mRNA levels decreased by 90 and 50%, respectively. Their mRNA levels were also transiently decreased by repeated IMO. MasR mRNA levels displayed a 75% transient decrease as well. Conversely, (P)RR mRNA levels were increased by 50% following single or repeated IMO. Because of its abundance, the function of the (P)RR was explored in PC-12 cells. Prorenin activation of the (P)RR increased phosphorylation of extracellular signal-regulated kinase 1/2 and tyrosine hydroxylase at Ser31, likely increasing its enzymatic activity and catecholamine biosynthesis. Together, the broad and dynamic changes in gene expression of the nonclassical RAS receptors implicate their role in the intricate response of the adrenomedullary catecholaminergic system to stress.

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.

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.

Targeted disruption of the bradykinin B2 receptor gene in mice alters the ontogeny of the renin-angiotensin system

2001 ◽  
Vol 281 (5) ◽  
pp. F795-F801 ◽  
Author(s):  
Igor V. Yosipiv ◽  
Susana Dipp ◽  
Samir S. El-Dahr
Keyword(s):  
Target Genes ◽  
Receptor Gene ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Protein Levels ◽  
Age Related ◽  
Renin Mrna ◽  
Renal Kallikrein

First published July 12, 2001; 10.1152/ajprenal.0020.2001.—Angiotensin II type 1 (AT1) receptor knockout (KO) mice exhibit an activated kallikrein-kinin system (KKS) that serves to attenuate the severity of the renal vascular phenotype in these mice (Tsuchida S, Miyazaki Y, Matsusaka T, Hunley TE, Inagami T, Fogo A, and Ichikawa I, Kidney Int 56: 509–516, 1999). Conversely, gestational high salt suppresses the fetal renin-angiotensin system (RAS) and provokes aberrant renal development in bradykinin B2-KO mice (El-Dahr SS, Harrison-Bernard LM, Dipp S, Yosipiv IV, and Meleg-Smith S, Physiol Genomics 3: 121–131, 2000). Thus the cross talk between the RAS and KKS may be critical for normal renal maturation. To further define the developmental interactions between the KKS and RAS, we examined the consequences of B2 receptor gene ablation on the expression of RAS components. Renal renin mRNA levels are 50% lower in newborn B2-KO than wild-type (WT) mice. Also, the age-related decline in renin mRNA is greater in B2-KO than WT mice (3.5- vs. 2-fold, P < 0.05). Although renal angiotensinogen (Ao) protein levels are higher in newborn B2-KO than WT mice, Ao mRNA levels are not, suggesting accumulation of Ao as a result of decreased renin-mediated cleavage. Similar age-related increases (8-fold) in angiotensin I-converting enzyme (ACE) activity are observed in B2-KO and WT mice. Renal AT1 protein levels are not different in B2-KO and WT mice. Furthermore, the developmental increases in renal kallikrein mRNA and enzymatic activity are more pronounced in B2-KO compared with WT mice (mRNA: 8- vs. 3-fold; activity: 13- vs. 6-fold, P < 0.05). We conclude that 1) bradykinin stimulates renin gene expression, 2) renal kallikrein is regulated via a negative feedback loop involving the B2 receptor, and 3) Ao, ACE, and AT1 are not bradykinin-target genes.

Intracardiac detection of angiotensinogen and renin: a localized renin-angiotensin system in neonatal rat heart

1992 ◽  
Vol 263 (4) ◽  
pp. C838-C850 ◽  
Author(s):  
D. E. Dostal ◽  
K. N. Rothblum ◽  
M. I. Chernin ◽  
G. R. Cooper ◽  
K. M. Baker
Keyword(s):  
Rat Heart ◽  
Messenger Rna ◽  
Renin Angiotensin System ◽  
Neonatal Rat ◽  
Immunofluorescent Staining ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Biological Studies ◽  
Renin Mrna ◽  
Neonatal Rat Heart

There is increasing evidence that the renin-angiotensin system (RAS) modulates cardiovascular function through both blood-borne and tissue-derived components. The existence of a local RAS has been proposed in the heart based on biochemical and molecular biological studies that identify angiotensinogen and renin. We conducted the present study to determine the chamber localization of angiotensinogen and renin mRNA in neonatal rat heart and whether these components could be identified in cultured cardiomyocytes and fibroblasts obtained from neonatal rat heart. Experiments using polymerase chain reaction (PCR) indicated that whole hearts obtained from neonatal rats contained both angiotensinogen and renin mRNA. With the use of radiolabeled cDNA probes and in situ hybridization, angiotensinogen and renin transcripts were localized both in the atria and ventricles of neonatal rat hearts. Relative signal strengths for angiotensinogen were highest in the left and right ventricles. In contrast, renin signal strength was overall much lower and preferentially localized in the left ventricle. To investigate the cellular source of angiotensinogen and renin, cultured neonatal heart cardiomyocytes and ventricular fibroblasts were screened for angiotensinogen and renin messenger RNA and protein using PCR and indirect immunofluorescent staining, respectively. These experiments demonstrated that both cell types produce transcripts and the respective translation products for angiotensinogen and renin. These data suggest that the site of angiotensin II synthesis can occur at the level of the individual cardiomyocyte and fibroblast, where it may serve to directly and/or indirectly regulate cardiac rate, force, growth, and development in the neonate.

Modification of sarcolemmal Na+-K+-ATPase and Na+/Ca2+ exchanger expression in heart failure by blockade of renin-angiotensin system

2005 ◽  
Vol 288 (6) ◽  
pp. H2637-H2646 ◽  
Author(s):  
Qiming Shao ◽  
Bin Ren ◽  
Vijayan Elimban ◽  
Paramjit S. Tappia ◽  
Nobuakira Takeda ◽  
...  
Keyword(s):  
Gene Expression ◽  
Heart Failure ◽  
Cardiac Hypertrophy ◽  
Protein Content ◽  
Ace Inhibitor ◽  
Renin Angiotensin System ◽  
Mrna Levels ◽  
Angiotensin System ◽  
Renin Angiotensin ◽  
Failing Heart

The activities of both sarcolemmal (SL) Na+-K+-ATPase and Na+/Ca2+ exchanger, which maintain the intracellular cation homeostasis, have been shown to be depressed in heart failure due to myocardial infarction (MI). Because the renin-angiotensin system (RAS) is activated in heart failure, this study tested the hypothesis that attenuation of cardiac SL changes in congestive heart failure (CHF) by angiotensin-converting enzyme (ACE) inhibitors is associated with prevention of alterations in gene expression for SL Na+-K+-ATPase and Na+/Ca2+ exchanger. CHF in rats due to MI was induced by occluding the coronary artery, and 3 wk later the animals were treated with an ACE inhibitor, imidapril (1 mg·kg−1·day−1), for 4 wk. Heart dysfunction and cardiac hypertrophy in the infarcted animals were associated with depressed SL Na+-K+-ATPase and Na+/Ca2+ exchange activities. Protein content and mRNA levels for Na+/Ca2+ exchanger as well as Na+-K+-ATPase α1-, α2- and β1-isoforms were depressed, whereas those for α3-isoform were increased in the failing heart. These changes in SL activities, protein content, and gene expression were attenuated by treating the infarcted animals with imidapril. The beneficial effects of imidapril treatment on heart function and cardiac hypertrophy as well as SL Na+-K+-ATPase and Na+/Ca2+ exchange activities in the infarcted animals were simulated by enalapril, an ACE inhibitor, and losartan, an angiotensin receptor antagonist. These results suggest that blockade of RAS in CHF improves SL Na+-K+-ATPase and Na+/Ca2+ exchange activities in the failing heart by preventing changes in gene expression for SL proteins.

Stretch-mediated activation of cardiac renin gene

1994 ◽  
Vol 267 (4) ◽  
pp. H1630-H1636 ◽  
Author(s):  
P. H. Boer ◽  
M. Ruzicka ◽  
W. Lear ◽  
E. Harmsen ◽  
J. Rosenthal ◽  
...  
Keyword(s):  
Polymerase Chain Reaction ◽  
Renin Angiotensin System ◽  
Volume Overload ◽  
Mrna Levels ◽  
Shunt Surgery ◽  
Chain Reaction ◽  
Angiotensin System ◽  
Renin Gene ◽  
Renin Mrna ◽  
Polymerase Chain

This study was designed to quantitate cardiac mRNA levels encoding components of the local renin-angiotensin system during the development of volume overload-induced cardiac hypertrophy. Changes in cardiac renin mRNA levels were measured in relation to renin activity in the left ventricle (LV) and in plasma after acute passive stretch of the heart caused by an aortovenocaval shunt in the rat. A quantitative reverse-transcriptase polymerase chain reaction method with competitive internal standards was used to measure mRNA levels in total RNA derived from cardiac tissues after shunt. Seven days after shunt surgery, LV weight was increased by 23%. Renin activities were elevated four- and twofold in plasma and LV, respectively. LV angiotensinogen mRNAs were not significantly increased by shunt surgery; they were twofold higher than phosphoglycerate kinase mRNA from the housekeeping gene PGK-1. By day 7, LV levels for renin mRNA were significantly increased from well below 0.25% to approximately 1% of PGK-1 mRNA. Identity between renin polymerase chain reaction products from kidney and heart cDNAs and absence of "reninlike" amplification products were supported by Southern blotting. Volume overload caused increased expression of the renin gene in the stretched myocardium. This finding is consistent with the concept of a myocardial renin-angiotensin system that can be activated by locally produced renin and contributes to the hypertrophy of cardiac muscle.

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