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Gene Review

Ren  -  renin

Rattus norvegicus

Synonyms: Angiotensinogenase, RATRENAA, RENAA, Ren1, Renin
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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


High impact information on Ren1


Chemical compound and disease context of Ren1


Biological context of Ren1


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 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


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].


  1. Renin and angiotensin II receptor gene expression in kidneys of renal hypertensive rats. Haefliger, J.A., Bergonzelli, G., Waeber, G., Aubert, J.F., Nussberger, J., Gavras, H., Nicod, P., Waeber, B. Hypertension (1995) [Pubmed]
  2. Cyclooxygenase-2 inhibition decreases renin content and lowers blood pressure in a model of renovascular hypertension. Wang, J.L., Cheng, H.F., Harris, R.C. Hypertension (1999) [Pubmed]
  3. A role for uric acid in the progression of renal disease. Kang, D.H., Nakagawa, T., Feng, L., Watanabe, S., Han, L., Mazzali, M., Truong, L., Harris, R., Johnson, R.J. J. Am. Soc. Nephrol. (2002) [Pubmed]
  4. Additive effects of enalapril and losartan in (mREN-2)27 transgenic rats. Richer, C., Bruneval, P., Ménard, J., Giudicelli, J.F. Hypertension (1998) [Pubmed]
  5. Angiotensin-converting enzyme is upregulated in the proximal tubules of rats with intense proteinuria. Largo, R., Gómez-Garre, D., Soto, K., Marrón, B., Blanco, J., Gazapo, R.M., Plaza, J.J., Egido, J. Hypertension (1999) [Pubmed]
  6. Effect of Losartan, a nonpeptide angiotensin II receptor antagonist, on drinking behavior and renal actions of centrally administered renin. Barbella, Y., Cierco, M., Israel, A. Proc. Soc. Exp. Biol. Med. (1993) [Pubmed]
  7. Toxicokinetic analysis of losartan during gestation and lactation in the rat. Spence, S.G., Zacchei, A.G., Lee, L.L., Baldwin, C.L., Berna, R.A., Mattson, B.A., Eydelloth, R.S. Teratology (1996) [Pubmed]
  8. The effects of perindopril and triple therapy in a normotensive model of diabetic nephropathy. O'Brien, R.C., Cooper, M.E., Jerums, G., Doyle, A.E. Diabetes (1993) [Pubmed]
  9. Vasopressin and renin response to dehydration in aged rats. Sladek, C.D., McNeill, T.H., Gregg, C.M., Blair, M.L., Baggs, R.B. Neurobiol. Aging (1981) [Pubmed]
  10. An inhibitory effect of dietary polyunsaturated fatty acids on renin secretion in the isolated perfused rat kidney. Codde, J.P., Croft, K.D., Barden, A., Mathews, E., Vandongen, R., Beilin, L.J. J. Hypertens. (1984) [Pubmed]
  11. Genetic determinants of diastolic and pulse pressure map to different loci in Lyon hypertensive rats. Dubay, C., Vincent, M., Samani, N.J., Hilbert, P., Kaiser, M.A., Beressi, J.P., Kotelevtsev, Y., Beckmann, J.S., Soubrier, F., Sassard, J. Nat. Genet. (1993) [Pubmed]
  12. Amino acid sequence of rat submaxillary tonin reveals similarities to serine proteases. Lazure, C., Leduc, R., Seidah, N.G., Thibault, G., Genest, J., Chrétien, M. Nature (1984) [Pubmed]
  13. Identity of angiotensinogen precursors of rat brain and liver. Campbell, D.J., Bouhnik, J., Ménard, J., Corvol, P. Nature (1984) [Pubmed]
  14. Renin-like effects of NGF evaluated using renin-angiotensin antagonists. Avrith, D.B., Lewis, M.E., Fitzsimons, J.T. Nature (1980) [Pubmed]
  15. Captopril (SQ 14225) depresses drinking and aldosterone in rats lacking vasopressin. Henderson, I.W., McKeever, A., Kenyon, C.J. Nature (1979) [Pubmed]
  16. AT1 receptor-mediated enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Prieto-Carrasquero, M.C., Kobori, H., Ozawa, Y., Gutiérrez, A., Seth, D., Navar, L.G. Am. J. Physiol. Renal Physiol. (2005) [Pubmed]
  17. Differential effects of angiotensin II on cardiac cell proliferation and intramyocardial perivascular fibrosis in vivo. McEwan, P.E., Gray, G.A., Sherry, L., Webb, D.J., Kenyon, C.J. Circulation (1998) [Pubmed]
  18. Coordinate expression of cyclooxygenase-2 and renin in the rat kidney in renovascular hypertension. Hartner, A., Goppelt-Struebe, M., Hilgers, K.F. Hypertension (1998) [Pubmed]
  19. Estrogen regulates angiotensin AT1 receptor expression via cytosolic proteins that bind to the 5' leader sequence of the receptor mRNA. Krishnamurthi, K., Verbalis, J.G., Zheng, W., Wu, Z., Clerch, L.B., Sandberg, K. Endocrinology (1999) [Pubmed]
  20. The tissue renin-angiotensin system in rats with fructose-induced hypertension: overexpression of type 1 angiotensin II receptor in adipose tissue. Giacchetti, G., Sechi, L.A., Griffin, C.A., Don, B.R., Mantero, F., Schambelan, M. J. Hypertens. (2000) [Pubmed]
  21. Effects of renin gene transfer on blood pressure and renin gene expression in a congenic strain of Dahl salt-resistant rats. St Lezin, E.M., Pravenec, M., Wong, A.L., Liu, W., Wang, N., Lu, S., Jacob, H.J., Roman, R.J., Stec, D.E., Wang, J.M., Reid, I.A., Kurtz, T.W. J. Clin. Invest. (1996) [Pubmed]
  22. Molecular cloning of rat renin cDNA and its gene. Burnham, C.E., Hawelu-Johnson, C.L., Frank, B.M., Lynch, K.R. Proc. Natl. Acad. Sci. U.S.A. (1987) [Pubmed]
  23. Activation of the rat renin promoter by HOXD10.PBX1b.PREP1, Ets-1, and the intracellular domain of notch. Pan, L., Glenn, S.T., Jones, C.A., Gross, K.W. J. Biol. Chem. (2005) [Pubmed]
  24. Nucleotide sequence of rat renin cDNA. Tada, M., Fukamizu, A., Seo, M.S., Takahashi, S., Murakami, K. Nucleic Acids Res. (1988) [Pubmed]
  25. Mast cells: a unique source of renin. Silver, R.B., Reid, A.C., Mackins, C.J., Askwith, T., Schaefer, U., Herzlinger, D., Levi, R. Proc. Natl. Acad. Sci. U.S.A. (2004) [Pubmed]
  26. An alternative transcript of the rat renin gene can result in a truncated prorenin that is transported into adrenal mitochondria. Clausmeyer, S., Stürzebecher, R., Peters, J. Circ. Res. (1999) [Pubmed]
  27. Angiotensin II attenuates renal cortical cyclooxygenase-2 expression. Cheng, H.F., Wang, J.L., Zhang, M.Z., Miyazaki, Y., Ichikawa, I., McKanna, J.A., Harris, R.C. J. Clin. Invest. (1999) [Pubmed]
  28. Inhibition of diabetic nephropathy by a decoy peptide corresponding to the "handle" region for nonproteolytic activation of prorenin. Ichihara, A., Hayashi, M., Kaneshiro, Y., Suzuki, F., Nakagawa, T., Tada, Y., Koura, Y., Nishiyama, A., Okada, H., Uddin, M.N., Nabi, A.H., Ishida, Y., Inagami, T., Saruta, T. J. Clin. Invest. (2004) [Pubmed]
  29. Upregulation of macula densa cyclooxygenase-2 expression is not dependent on glomerular filtration. Schweda, F., Kammerl, M., Wagner, C., Krämer, B.K., Kurtz, A. Am. J. Physiol. Renal Physiol. (2004) [Pubmed]
  30. Chronic cyclooxygenase-2 inhibition blunts low sodium-stimulated renin without changing renal haemodynamics. Harding, P., Carretero, O.A., Beierwaltes, W.H. J. Hypertens. (2000) [Pubmed]
  31. Renin inhibition attenuates insulin resistance, oxidative stress, and pancreatic remodeling in the transgenic Ren2 rat. Habibi, J., Whaley-Connell, A., Hayden, M.R., DeMarco, V.G., Schneider, R., Sowers, S.D., Karuparthi, P., Ferrario, C.M., Sowers, J.R. Endocrinology (2008) [Pubmed]
  32. Formation of angiotensin II by tonin-inhibitor complex. Ikeda, M., Sasaguri, M., Maruta, H., Arakawa, K. Hypertension (1988) [Pubmed]
  33. Attenuation of genetic hypertension after short-term vasopressin V1A receptor antagonism. Burrell, L.M., Phillips, P.A., Risvanis, J., Aldred, K.L., Hutchins, A.M., Johnston, C.I. Hypertension (1995) [Pubmed]
  34. Enhancement of collecting duct renin in angiotensin II-dependent hypertensive rats. Prieto-Carrasquero, M.C., Harrison-Bernard, L.M., Kobori, H., Ozawa, Y., Hering-Smith, K.S., Hamm, L.L., Navar, L.G. Hypertension (2004) [Pubmed]
  35. Effects of long-term inhibition of neuronal nitric oxide synthase on blood pressure and renin release. Ollerstam, A., Skøtt, O., Ek, J., Persson, A.E., Thorup, C. Acta Physiol. Scand. (2001) [Pubmed]
  36. Angiotensin subtype-2 receptors inhibit renin biosynthesis and angiotensin II formation. Siragy, H.M., Xue, C., Abadir, P., Carey, R.M. Hypertension (2005) [Pubmed]
  37. Inhibition of COX-2 counteracts the effects of diuretics in rats. Kammerl, M.C., Nüsing, R.M., Richthammer, W., Krämer, B.K., Kurtz, A. Kidney Int. (2001) [Pubmed]
  38. Angiotensinogen depletion by high renin levels in hypertensive rats: no evidence for tonic stimulation of angiotensinogen by angiotensin II. Gahnem, F., Camargo, M.J., von Lutterotti, N., Laragh, J.H., Sealey, J.E. J. Hypertens. (1995) [Pubmed]
  39. Cyclooxygenase-2 contributes to elevated renin in the early postnatal period in rats. Stubbe, J., Jensen, B.L., Bachmann, S., Morsing, P., Skøtt, O. Am. J. Physiol. Regul. Integr. Comp. Physiol. (2003) [Pubmed]
  40. Nitric oxide synthase mRNA levels correlate with gene expression of angiotensin II type-1 but not type-2 receptors, renin or angiotensin converting enzyme in selected brain areas. Krizanová, O., Kiss, A., Záciková, L., Jezová, D. Physiological research / Academia Scientiarum Bohemoslovaca. (2001) [Pubmed]
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