Disease relevance of Ren1

• The aim of this investigation was to examine the interrelation between renal mRNA levels of renin and angiotensin II receptor type 1 (AT1) in a renin-dependent form of experimental hypertension [1].
• It has been proposed that the macula densa participates in the regulation of increased renin expression in renovascular hypertension (RVH) and that prostaglandins may be among the mediators of macula densa function [2].
• To better understand the mechanism for the vascular disease, the expression of COX-2 and renin were examined [3].
• We studied whether chronic and simultaneous administration of enalapril and losartan would result in additive or synergistic effects in the (mREN-2)27 transgenic rat (TGR), the investigated targets being blood pressure, cardiac hypertrophy, renin-angiotensin system blockade achieved, and plasma active renin concentration [4].
• Our results show that in the kidney of rats with intense proteinuria, ACE and angiotensinogen were upregulated, while gene expression of renin was inhibited and AT1 was unmodified [5].

Psychiatry related information on Ren1

• Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin [6].
• Furthermore, the maximum exposure to losartan and EXP3174 correlates with the ontogeny of the renin angiotensin system on approximately GD 17 and the critical period for losartan-induced renal lesions (GD15-20) [7].
• A similar rise in plasma renin activity occurred in the two groups receiving antihypertensive drugs, whereas the perindopril but not the triple therapy group had suppressed plasma angiotensin-converting enzyme activity [8].
• The increase in serum vasopressin (VP) and renin concentrations observed in the 3 month animals following chronic water deprivation were absent in the aged rats (p less than 0.05 and p less than 0.02, respectively) [9].
• The influence of dietary modification of polyunsaturated fatty acids (PUFA) on renin secretion, renal vascular tone and prostanoid excretion was studied in isolated perfused rat kidneys under basal conditions and in response to angiotensin II [10].

High impact information on Ren1

• Significant linkage was established between diastolic blood pressure and a microsatellite marker of the renin gene (REN) on rat chromosome 13, and between pulse pressure and the carboxypeptidase B gene (CPB) on chromosome 2 [11].
• The substrate specificity of tonin shows that it differs from kallikreins and is definitely not a renin-like enzyme or an angiotensin-converting enzyme [12].
• Whereas many different enzymes are able to cleave angiotensinogen (renin substrate) to release angiotensin I (AI) or angiotensin II (AII), angiotensinogen is the only known precursor of AI and AII [13].
• Intracranial injection of angiotensin II (AII) or activation of the cerebral isorenin-angiotensin system with intracranial renin causes an immediate thirst and a delayed sodium appetite in the rat [14].
• We conclude that the polydipsia of diabetes insipidus partly results from elevated plasma renin activities and angiotensin II concentrations seen in this syndrome [15].

Chemical compound and disease context of Ren1

• The augmented distal tubular renin may contribute to increased intratubular ANG II levels and distal nephron sodium reabsorption in ANG II-dependent hypertension [16].
• The effects are independent of aldosterone and blood pressure and have important implications in renin-dependent hypertension and chronic cardiac failure when circulating Ang II is elevated [17].
• We tested the hypothesis that the inducible isoform of prostaglandin G/H synthase, cyclooxygenase-2, contributes to the stimulation of renin synthesis in renovascular hypertension [18].
• Two of the most highly recognized factors implicated in the pathogenesis of hypertension, atherosclerosis, congestive heart failure and associated cardiovascular disease are the renin angiotensin system (RAS) and estrogen [19].
• DESIGN AND METHODS: To investigate the role of the renin-angiotensin system in fructose-induced hypertension we measured angiotensinogen, renin and angiotensin II type 1 (AT1) receptor mRNA levels in tissues of Sprague-Dawley rats that were fed either standard rat chow or a diet containing 66% fructose [20].

Biological context of Ren1

• Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats [21].
• This rat cDNA was used to isolate the complete copy of a renin gene from a rat genomic library, and a comparison of this genomic clone with rat genomic DNA showed that renin is a single-copy gene in the rat [22].
• We have isolated full-length cDNAs for renin from a rat kidney cDNA library [22].
• Renin gene expression is subject to complex developmental and tissue-specific regulation [23].
• Nucleotide sequence of rat renin cDNA [24].

Anatomical context of Ren1

• Mast cells: a unique source of renin [25].
• Characterization of the local renin-angiotensin system in the rat adrenal zona glomerulosa indicated a dual targeting of renin both to the secretory pathway and mitochondria [26].
• To investigate the transport of renin into mitochondria, we constructed a series of amino-terminal deletion variants of preprorenin [26].
• Finally, we show that the intracellular domain of Notch1, Ets-1, and HOXD10.PBX1b.PREP1 activate the rat renin promoter cooperatively in COS-7 cells [23].
• Renin protein levels measured in the kidney medulla, to avoid contribution from juxtaglomerular apparatus cells, were higher in ANG II-infused rats [1.64 +/- 0.3 vs. 1.00 +/- 0.1 densitometric units (DU) compared with sham-operated rats; P < 0.05], and ARB treatment prevented this increase (1.01 +/- 0.1) [16].

Associations of Ren1 with chemical compounds

• To determine whether increased COX-2expression in response to ACE inhibition mediated increases in renin production, rats were treated with captopril for one week with or without the specific COX-2 inhibitor, SC58236 [27].
• Metabolic and renal histological changes and the renin-Ang system components in the plasma and kidneys were determined at 8, 16, and 24 weeks following streptozotocin treatment [28].
• Renin (EC 3.4.23.15) is an aspartyl protease that cleaves its only known substrate, angiotensinogen, to release the vasopressor hormone angiotensin [22].
• Renin mRNA expression was regulated strictly in parallel in both kidneys, a low-salt diet or furosemide treatment stimulating and a high-salt diet suppressing it [29].
• Chronic treatment with NS 398 did not decrease renal renin content (31.8 +/- 1.8 versus 33.5 +/- 2.6 ng Ang I/ mg per h, with NS 398 versus controls), nor did it influence systemic blood pressure or renal haemodynamics [30].
• Collectively, these data suggest that pancreatic functional/structural changes are driven, in part, by tissue renin-angiotensin system-mediated increases in NADPH oxidase and reactive oxygen species generation, abnormalities attenuated with direct renin inhibition [31].

Physical interactions of Ren1

• However, the solid-phase antibody-bound tonin-alpha 1-macroglobulin complex could not hydrolyze the plasma protein renin substrate [32].
• Results of vasopressin V1A receptor binding kinetics and plasma renin or aldosterone concentrations did not suggest a lasting effect of OPC-21268 on the vasopressin system or of ramipril on the renin-angiotensin system following treatment withdrawal.(ABSTRACT TRUNCATED AT 250 WORDS)[33]

Co-localisations of Ren1

• Tubular renin immunostaining was apically distributed in principal cells colocalizing with aquaporin-2 in connecting tubules and cortical and medullary collecting ducts [34].

Regulatory relationships of Ren1

• Chronic cyclooxygenase-2 inhibition blunts low sodium-stimulated renin without changing renal haemodynamics [30].
• This suggests that inhibition of nNOS stimulates renin release but that this stimulatory effect in the long run might be depressed by the increase in blood pressure [35].
• We hypothesized that AT2 receptors inhibit angiotensin II (Ang II) through inhibition of renin biosynthesis [36].
• BACKGROUND: It is well established that the diuretic- and renin-stimulated effects of loop diuretics can be attenuated by nonselective cyclooxygenase inhibitors [37].
• In the present study we used the Ang II subtype 1 (AT1) receptor antagonist losartan to investigate whether rising plasma Ang II levels stimulate angiotensinogen production to counteract the falling plasma angiotensinogen levels caused by increasing renin activity in plasma [38].

Other interactions of Ren1

• Cyclooxygenase-2 inhibition decreases renin content and lowers blood pressure in a model of renovascular hypertension [2].
• This is supported by the significant inverse correlation (r = .71, P < .01) between plasma renin activity and AT1A mRNA expression measured in the clipped kidney of the hypertensive rats [1].
• Inhibition of angiotensin AT(1) receptors by candesartan from postnatal day 1 to day 5 increased COX-2 mRNA (2.5-fold), protein, and distribution, renin mRNA (7-fold) and PRC (20- to 70-fold), but had no influence on COX-1 mRNA [39].
• Moreover, a significant correlation was found between brain NO synthase and AT1 receptor mRNAs, but not with mRNA of the AT2 receptor, ACE and renin [40].
• Renin qRTPCR in ANG II-infused rats showed higher mRNA levels in the kidney medulla compared with sham-operated rats (5.5 +/- 2.3 vs. 0.04 +/- 0.02 ratio to GAPDH mRNA levels; P < 0.001); however, renin transcript levels were normalized in the ARB-treated rats [16].

Analytical, diagnostic and therapeutic context of Ren1

• The HMC-1 renin RT-PCR product is 100% homologous to Homo sapiens renin [25].
• Molecular cloning of rat renin cDNA and its gene [22].
• An Ets-binding site (-143 to -138 bp) has also been identified in the rat renin promoter by sequence comparisons and electrophoretic mobility shift assays [23].
• Northern blot analysis of polyA+ RNA obtained from the kidneys of renal hypertensive rats showed increased levels of renin mRNA in the clipped kidney, whereas a decrease was observed in the unclipped kidney [1].
• After 1 wk of ligation, the animals were treated with subcutaneous infusions of furosemide (12 mg x kg(-1) x day(-1)) or with a low-salt or a high-salt diet (0.02% wt/wt; 8% wt/wt), and COX-2 as well as renin mRNA expression were determined in the ligated and the nonligated contralateral kidney [29].

References