Skip to main content
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1986 Jul;78(1):31–39. doi: 10.1172/JCI112566

Angiotensinogen gene is expressed and differentially regulated in multiple tissues of the rat.

D J Campbell, J F Habener
PMCID: PMC329527  PMID: 3013940

Abstract

To define the role of local synthesis of angiotensinogen in tissue angiotensin production, we have quantitated angiotensinogen messenger RNA (mRNA) levels in 17 different tissues of four groups of rats: control rats, nephrectomized rats, rats given dexamethasone, ethynylestradiol, and triiodothyronine, and nephrectomized rats given dexamethasone, ethynylestradiol, and triiodothyronine. Angiotensinogen mRNA was identified in 12 tissues: liver, kidney, brain, spinal cord, aorta, mesentery, atria, lung, adrenal, large intestine, stomach, and spleen. Angiotensinogen mRNA was not identified in pituitary, ventricle, testis, small intestine, or pancreas. When expressed per gram tissue wet weight, angiotensinogen mRNA levels of extrahepatic tissues were less than 4% of hepatic levels. However, when expressed per milligram total RNA, angiotensinogen mRNA levels of brain, spinal cord, aorta, and mesentery were 26-42% of hepatic levels. Regulation of angiotensinogen mRNA levels was tissue specific. This demonstration of a widespread tissue distribution of angiotensinogen mRNA may indicate a similarly widespread distribution of local angiotensin systems that are independent of the circulating renin-angiotensin system.

Full text

PDF
31

Images in this article

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Aguilera G., Schirar A., Baukal A., Catt K. J. Circulating angiotensin II and adrenal receptors after nephrectomy. Nature. 1981 Feb 5;289(5797):507–509. doi: 10.1038/289507a0. [DOI] [PubMed] [Google Scholar]
  2. Arakawa K., Yuki M., Ikeda M. Chemical identity of tryptensin with angiotensin. Biochem J. 1980 Jun 1;187(3):647–653. doi: 10.1042/bj1870647. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blumberg A. L., Denny S. E., Marshall G. R., Needleman P. Blood vessel-hormone interactions: angiotensin, bradykinin, and prostaglandins. Am J Physiol. 1977 Mar;232(3):H305–H310. doi: 10.1152/ajpheart.1977.232.3.H305. [DOI] [PubMed] [Google Scholar]
  4. Boucher R., Demassieux S., Garcia R., Genest J. Tonin, angiotensin II system. A review. Circ Res. 1977 Oct;41(4 Suppl 2):26–29. doi: 10.1161/01.res.41.4.26. [DOI] [PubMed] [Google Scholar]
  5. Campbell D. J., Bouhnik J., Coezy E., Pinet F., Clauser E., Menard J., Corvol P. Characterization of precursor and secreted forms of rat angiotensinogen. Endocrinology. 1984 Mar;114(3):776–785. doi: 10.1210/endo-114-3-776. [DOI] [PubMed] [Google Scholar]
  6. Campbell D. J., Bouhnik J., Ménard J., Corvol P. Identity of angiotensinogen precursors of rat brain and liver. Nature. 1984 Mar 8;308(5955):206–208. doi: 10.1038/308206a0. [DOI] [PubMed] [Google Scholar]
  7. Campbell D. J. The site of angiotensin production. J Hypertens. 1985 Jun;3(3):199–207. doi: 10.1097/00004872-198506000-00002. [DOI] [PubMed] [Google Scholar]
  8. Celio M. R., Inagami T. Angiotensin II immunoreactivity coexists with renin in the juxtaglomerular granular cells of the kidney. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3897–3900. doi: 10.1073/pnas.78.6.3897. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Chirgwin J. M., Przybyla A. E., MacDonald R. J., Rutter W. J. Isolation of biologically active ribonucleic acid from sources enriched in ribonuclease. Biochemistry. 1979 Nov 27;18(24):5294–5299. doi: 10.1021/bi00591a005. [DOI] [PubMed] [Google Scholar]
  10. Clauser E., Bouhnik J., Coezy E., Corvol P., Menard J. Synthesis and release of immunoreactive angiotensinogen by rat liver slices. Endocrinology. 1983 Apr;112(4):1188–1193. doi: 10.1210/endo-112-4-1188. [DOI] [PubMed] [Google Scholar]
  11. De Fernández M. T., Paladini A. C., Delius A. E. Isolation and identification of a pepsitensin. Biochem J. 1965 Nov;97(2):540–546. doi: 10.1042/bj0970540. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Desjardins-Giasson S., Gutkowska J., Garcia R., Genest J. Renin substrate in rat mesenteric artery. Can J Physiol Pharmacol. 1981 Jun;59(6):528–532. doi: 10.1139/y81-079. [DOI] [PubMed] [Google Scholar]
  13. Dorer F. E., Lentz K. E., Kahn J. R., Levine M., Skeggs L. T. A comparison of the substrate specificities of cathepsin D and pseudorenin. J Biol Chem. 1978 May 10;253(9):3140–3142. [PubMed] [Google Scholar]
  14. Dzau V. J., Brenner A., Emmett N., Haber E. Identification of renin and renin-like enzymes in rat brain by a renin-specific antibody. Clin Sci (Lond) 1980 Dec;59 (Suppl 6):45s–47s. doi: 10.1042/cs059045s. [DOI] [PubMed] [Google Scholar]
  15. Favaloro J., Treisman R., Kamen R. Transcription maps of polyoma virus-specific RNA: analysis by two-dimensional nuclease S1 gel mapping. Methods Enzymol. 1980;65(1):718–749. doi: 10.1016/s0076-6879(80)65070-8. [DOI] [PubMed] [Google Scholar]
  16. Fernandez L. A., Twickler J., Mead A. Neovascularization produced by angiotensin II. J Lab Clin Med. 1985 Feb;105(2):141–145. [PubMed] [Google Scholar]
  17. Field L. J., McGowan R. A., Dickinson D. P., Gross K. W. Tissue and gene specificity of mouse renin expression. Hypertension. 1984 Jul-Aug;6(4):597–603. doi: 10.1161/01.hyp.6.4.597. [DOI] [PubMed] [Google Scholar]
  18. Fordis C. M., Megorden J. S., Ropchak T. G., Keiser H. R. Absence of renin-like activity in rat aorta and microvessels. Hypertension. 1983 Sep-Oct;5(5):635–641. doi: 10.1161/01.hyp.5.5.635. [DOI] [PubMed] [Google Scholar]
  19. Ganong W. F. The brain renin-angiotensin system. Annu Rev Physiol. 1984;46:17–31. doi: 10.1146/annurev.ph.46.030184.000313. [DOI] [PubMed] [Google Scholar]
  20. Ganten D., Hermann K., Unger T., Lang R. E. The tissue renin-angiotensin systems: focus on brain angiotensin, adrenal gland and arterial wall. Clin Exp Hypertens A. 1983;5(7-8):1099–1118. doi: 10.3109/10641968309048844. [DOI] [PubMed] [Google Scholar]
  21. Gregory T. J., Wallis C. J., Printz M. P. Regional changes in rat brain angiotensinogen following bilateral nephrectomy. Hypertension. 1982 Nov-Dec;4(6):827–838. doi: 10.1161/01.hyp.4.6.827. [DOI] [PubMed] [Google Scholar]
  22. Gunther S., Gimbrone M. A., Jr, Alexander R. W. Regulation by angiotensin II of its receptors in resistance blood vessels. Nature. 1980 Sep 18;287(5779):230–232. doi: 10.1038/287230a0. [DOI] [PubMed] [Google Scholar]
  23. Haas E., Lewis L. V., Scipione P., Koshy T. J., Varde A. U., Renerts L. Angiotensin-producing enzyme I of serum: formation by immunization with renin. J Hypertens. 1984 Apr;2(2):131–140. doi: 10.1097/00004872-198404000-00003. [DOI] [PubMed] [Google Scholar]
  24. Hasegawa H., Shainoff J. R., Lewis L. A., Masson G. M. Further evidence for the existence of angiotensinogen stimulating activity (ASA) after nephrectomy. Proc Soc Exp Biol Med. 1976 Oct;153(1):37–43. doi: 10.3181/00379727-153-39476. [DOI] [PubMed] [Google Scholar]
  25. Herrmann H. C., Dzau V. J. The feedback regulation of angiotensinogen production by components of the renin-angiotensin system. Circ Res. 1983 Mar;52(3):328–334. doi: 10.1161/01.res.52.3.328. [DOI] [PubMed] [Google Scholar]
  26. Hobart P. M., Shen L. P., Crawford R., Pictet R. L., Rutter W. J. Comparison of the nucleic acid sequence of anglerfish and mammalian insulin mRNA's from cloned cDNA's. Science. 1980 Dec 19;210(4476):1360–1363. doi: 10.1126/science.7001633. [DOI] [PubMed] [Google Scholar]
  27. Husain A., Smeby R. R., Wilk D., Dzau V. J., Bumpus F. M. Biochemical and immunological properties of dog brain isorenin. Endocrinology. 1984 Jun;114(6):2210–2215. doi: 10.1210/endo-114-6-2210. [DOI] [PubMed] [Google Scholar]
  28. Levens N. R., Peach M. J., Carey R. M. Role of the intrarenal renin-angiotensin system in the control of renal function. Circ Res. 1981 Feb;48(2):157–167. doi: 10.1161/01.res.48.2.157. [DOI] [PubMed] [Google Scholar]
  29. Lewicki J. A., Fallon J. H., Printz M. P. Regional distribution of angiotensinogen in rat brain. Brain Res. 1978 Dec 15;158(2):359–371. doi: 10.1016/0006-8993(78)90681-9. [DOI] [PubMed] [Google Scholar]
  30. Lilly L. S., Pratt R. E., Alexander R. W., Larson D. M., Ellison K. E., Gimbrone M. A., Jr, Dzau V. J. Renin expression by vascular endothelial cells in culture. Circ Res. 1985 Aug;57(2):312–318. doi: 10.1161/01.res.57.2.312. [DOI] [PubMed] [Google Scholar]
  31. Lind R. W., Swanson L. W., Ganten D. Organization of angiotensin II immunoreactive cells and fibers in the rat central nervous system. An immunohistochemical study. Neuroendocrinology. 1985 Jan;40(1):2–24. doi: 10.1159/000124046. [DOI] [PubMed] [Google Scholar]
  32. Loudon M., Bing R. F., Thurston H., Swales J. D. Arterial wall uptake of renal renin and blood pressure control. Hypertension. 1983 Sep-Oct;5(5):629–634. doi: 10.1161/01.hyp.5.5.629. [DOI] [PubMed] [Google Scholar]
  33. Maruta H., Arakawa K. Confirmation of direct angiotensin formation by kallikrein. Biochem J. 1983 Jul 1;213(1):193–200. doi: 10.1042/bj2130193. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Menard J., Galen F. X., Devaux C., Kopp N., Auzan C., Corvol P. Immunochemical differences between angiotensin I-forming enzymes in man. Clin Sci (Lond) 1980 Dec;59 (Suppl 6):41s–44s. doi: 10.1042/cs059041s. [DOI] [PubMed] [Google Scholar]
  35. Misumi J., Bouhnik J., Alhenc-Gelas F., Corvol P., Ménard J. Effects of circulating renin substrate on renal function in isolated perfused rat kidney. J Hypertens Suppl. 1983 Dec;1(2):40–42. [PubMed] [Google Scholar]
  36. Morris B. J., Johnston C. I. Renin substrate in granules from rat kidney cortex. Biochem J. 1976 Mar 15;154(3):625–637. doi: 10.1042/bj1540625. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Naruse K., Inagami T., Celio M. R., Workman R. J., Takii Y. Immunohistochemical evidence that angiotensins I and II are formed by intracellular mechanism in juxtaglomerular cells. Hypertension. 1982 May-Jun;4(3 Pt 2):70–74. [PubMed] [Google Scholar]
  38. Naruse K., Takii Y., Inagami T. Immunohistochemical localization of renin in luteinizing hormone-producing cells of rat pituitary. Proc Natl Acad Sci U S A. 1981 Dec;78(12):7579–7583. doi: 10.1073/pnas.78.12.7579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Navar L. G., Rosivall L. Contribution of the renin-angiotensin system to the control of intrarenal hemodynamics. Kidney Int. 1984 Jun;25(6):857–868. doi: 10.1038/ki.1984.102. [DOI] [PubMed] [Google Scholar]
  40. Nieuwenhuis J. J., Theron J. J. Cardiac substances that influence blood-pressure. II. Potent pressor activity in rat and rabbit atrial muscle. Biochem Biophys Res Commun. 1985 Jun 14;129(2):472–478. doi: 10.1016/0006-291x(85)90175-5. [DOI] [PubMed] [Google Scholar]
  41. Ohkubo H., Kageyama R., Ujihara M., Hirose T., Inayama S., Nakanishi S. Cloning and sequence analysis of cDNA for rat angiotensinogen. Proc Natl Acad Sci U S A. 1983 Apr;80(8):2196–2200. doi: 10.1073/pnas.80.8.2196. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Okamura T., Clemens D. L., Inagami T. Generation of angiotensins in cultured pheochromocytoma cells. Neurosci Lett. 1984 May 4;46(2):151–156. doi: 10.1016/0304-3940(84)90433-6. [DOI] [PubMed] [Google Scholar]
  43. Pandey K. N., Maki M., Inagami T. Detection of renin mRNA in mouse testis by hybridization with renin cDNA probe. Biochem Biophys Res Commun. 1984 Dec 14;125(2):662–667. doi: 10.1016/0006-291x(84)90590-4. [DOI] [PubMed] [Google Scholar]
  44. Pandey K. N., Misono K. S., Inagami T. Evidence for intracellular formation of angiotensins: coexistence of renin and angiotensin-converting enzyme in Leydig cells of rat testis. Biochem Biophys Res Commun. 1984 Aug 16;122(3):1337–1343. doi: 10.1016/0006-291x(84)91238-5. [DOI] [PubMed] [Google Scholar]
  45. Peach M. J. Renin-angiotensin system: biochemistry and mechanisms of action. Physiol Rev. 1977 Apr;57(2):313–370. doi: 10.1152/physrev.1977.57.2.313. [DOI] [PubMed] [Google Scholar]
  46. Re R., Fallon J. T., Dzau V., Quay S. C., Haber E. Renin synthesis by canine aortic smooth muscle cells in culture. Life Sci. 1982 Jan 4;30(1):99–106. doi: 10.1016/0024-3205(82)90641-5. [DOI] [PubMed] [Google Scholar]
  47. Reilly C. F., Tewksbury D. A., Schechter N. M., Travis J. Rapid conversion of angiotensin I to angiotensin II by neutrophil and mast cell proteinases. J Biol Chem. 1982 Aug 10;257(15):8619–8622. [PubMed] [Google Scholar]
  48. Richoux J. P., Cordonnier J. L., Bouhnik J., Clauser E., Corvol P., Menard J., Grignon G. Immunocytochemical localization of angiotensinogen in rat liver and kidney. Cell Tissue Res. 1983;233(2):439–451. doi: 10.1007/BF00238309. [DOI] [PubMed] [Google Scholar]
  49. Sernia C., Mowchanuk M. D. Brain angiotensinogen: in vitro synthesis and chromatographic characterization. Brain Res. 1983 Jan 24;259(2):275–283. doi: 10.1016/0006-8993(83)91258-1. [DOI] [PubMed] [Google Scholar]
  50. Sernia C., Reid I. A. Release of angiotensinogen by rat brain in vitro. Brain Res. 1980 Jun 16;192(1):217–225. doi: 10.1016/0006-8993(80)91021-5. [DOI] [PubMed] [Google Scholar]
  51. Steele M. K., Brownfield M. S., Ganong W. F. Immunocytochemical localization of angiotensin immunoreactivity in gonadotropes and lactotropes of the rat anterior pituitary gland. Neuroendocrinology. 1982;35(3):155–158. doi: 10.1159/000123373. [DOI] [PubMed] [Google Scholar]
  52. Swales J. D., Abramovici A., Beck F., Bing R. F., Loudon M., Thurston H. Arterial wall renin. J Hypertens Suppl. 1983 Oct;1(1):17–22. [PubMed] [Google Scholar]
  53. Swales J. D. Arterial wall or plasma renin in hypertension? Clin Sci (Lond) 1979 Apr;56(4):293–298. doi: 10.1042/cs0560293. [DOI] [PubMed] [Google Scholar]
  54. Tanaka T., Ohkubo H., Nakanishi S. Common structural organization of the angiotensinogen and the alpha 1-antitrypsin genes. J Biol Chem. 1984 Jul 10;259(13):8063–8065. [PubMed] [Google Scholar]
  55. Taugner R., Hackenthal E., Helmchen U., Ganten D., Kugler P., Marin-Grez M., Nobiling R., Unger T., Lockwald I., Keilbach R. The intrarenal renin-angiotensin-system. An immunocytochemical study on the localization of renin, angiotensinogen, converting enzyme and the angiotensins in the kidney of mouse and rat. Klin Wochenschr. 1982 Oct 1;60(19):1218–1222. doi: 10.1007/BF01716726. [DOI] [PubMed] [Google Scholar]
  56. Thomas P. S. Hybridization of denatured RNA transferred or dotted nitrocellulose paper. Methods Enzymol. 1983;100:255–266. doi: 10.1016/0076-6879(83)00060-9. [DOI] [PubMed] [Google Scholar]
  57. Tonnesen M. G., Klempner M. S., Austen K. F., Wintroub B. U. Identification of a human neutrophil angiotension II-generating protease as cathepsin G. J Clin Invest. 1982 Jan;69(1):25–30. doi: 10.1172/JCI110437. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Wallis C. J., Printz M. P. Adrenal regulation of regional brain angiotensinogen content. Endocrinology. 1980 Jan;106(1):337–342. doi: 10.1210/endo-106-1-337. [DOI] [PubMed] [Google Scholar]
  59. Zern M. A., Yap S. H., Strair R. K., Kaysen G. A., Shafritz D. A. Effects of chronic renal failure on protein synthesis and albumin messenger ribonucleic acid in rat liver. J Clin Invest. 1984 Apr;73(4):1167–1174. doi: 10.1172/JCI111302. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES