Advertisement

Molecular and Cellular Biochemistry

, Volume 296, Issue 1–2, pp 25–34 | Cite as

Rhythmic clock gene expression in heart, kidney and some brain nuclei involved in blood pressure control in hypertensive TGR(mREN-2)27 rats

  • Iveta Herichová
  • Boris Mravec
  • Katarína Stebelová
  • Ol’ga Križanová
  • Dana Jurkovičová
  • Richard Kvetňanský
  • Michal Zeman
Article

Abstract

Hypertensive TGR(mREN-2)27 rats exerting inverted blood pressure (BP) profile were used to study clock gene expression in structures responsible for BP control. TGR and control Sprague Dawley male rats were synchronized to the light:dark cycle 12:12 with food and water ad libitum. Daily rhythm in per2, bmal1, clock and dbp expression in the suprachiasmatic nucleus (SCN), rostral ventrolateral medulla (RVLM), nucleus of the solitary tract (NTS), heart and kidney was determined in both groups. Sampling occurred in regular 4 h intervals when rats of both strains were 11-weeks-old. Blood pressure and relative heart weight were significantly elevated in TGR rats in comparison with control. Expression of bmal1 and clock was up regulated in SCN of TGR rats but daily rhythm in per2 and dbp expression was similar in both groups. Mesor of per2 expression in RVLM was significantly higher in TGR than in control rats. In NTS of TGR rats expression of per2 was phase delayed by 3.5 h in comparison with control and bmal1 did not exert rhythmic pattern. Our study provided the first evidence about modified function of central and peripheral circadian oscillators in TGR rats at the level of clock gene expression. Expression of clock genes exerted up regulation in SCN and RVLM and down regulation in NTS. Circadian oscillators in selected brain structures were influenced more than oscillators in the heart and kidney by additional renin gene. Interactions of RAS and circadian system probably contribute to the development of inverted BP profile in TGR rats.

Key words

clock genes medulla SCN blood pressure hypertension 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

Notes

Acknowledgments

This study was supported by Science and Technology Assistance Agency under the contract No. APVT-20–022704 and SP 51/0280800/02808021. Authors are grateful to Dr. L. Červenka and Prof. M. Bader for providing experimental animals.

References

  1. 1.
    Guo H, Brewer JM, Champhekar A, Harris RB, Bittman EL (2005) Differential control of peripheral circadian rhythms by suprachiasmatic-dependent neural signals. Proc Natl Acad Sci USA 102: 3111–3116 PubMedCrossRefGoogle Scholar
  2. 2.
    Pando MP, Morse D, Cermakian N, Sassone-Corsi P (2002) Phenotypic rescue of a peripheral clock genetic defect via SCN hierarchical dominance. Cell 110: 107–117 PubMedCrossRefGoogle Scholar
  3. 3.
    Silver R, LeSauter J, Tresco PA, Lehman MN (1996) A diffusible coupling signal from the transplanted suprachiasmatic nucleus controlling circadian locomotor rhythms. Nature 382: 810–813PubMedCrossRefGoogle Scholar
  4. 4.
    Hogenesch JB, Gu YZ, Jain S, Bradfield CA (1998) The basic-helix–loop-helix-PAS orphan MOP3 forms transcriptionally active complexes with circadian and hypoxia factors. Proc Natl Acad Sci USA 95: 5474–5479 PubMedCrossRefGoogle Scholar
  5. 5.
    Kume K, Zylka MJ, Sriram S, Shearman LP, Weaver DR, Jin X, Maywood ES, Hastings MH, Reppert SM (1999) mCRY1 and mCRY2 are essential components of the negative limb of the circadian clock feedback loop. Cell 98: 193–205 PubMedCrossRefGoogle Scholar
  6. 6.
    Shearman LP, Zylka MJ, Weaver DR, Kolakowski LF Jr., Reppert SM (1997) Two period homologs: circadian expression and photic regulation in the suprachiasmatic nuclei. Neuron 19: 1261–1269 PubMedCrossRefGoogle Scholar
  7. 7.
    Sun ZS, Albrecht U, Zhuchenko O, Bailey J, Eichele G, Lee CC (1997) RIGUI, a putative mammalian ortholog of the Drosophila period gene. Cell 90: 1003–1011 PubMedCrossRefGoogle Scholar
  8. 8.
    Vitaterna MH, King DP, Chang AM, Kornhauser JM, Lowrey PL, McDonald JD, Dove WF, Pinto LH, Turek FW, Takahashi JS (1994) Mutagenesis and mapping of a mouse gene, Clock, essential for circadian behavior. Science 264: 719–725 PubMedCrossRefGoogle Scholar
  9. 9.
    Takahashi JS (2004) Finding new Clock components: past and future. J Biol Rhythms 19: 339–347 PubMedCrossRefGoogle Scholar
  10. 10.
    Lemmer B, Mattes A, Bohm M, Ganten D (1993) Circadian blood pressure variation in transgenic hypertensive rats. Hypertension 22: 97–101 PubMedGoogle Scholar
  11. 11.
    Shimamura T, Nakajima M, Iwasaki T, Hayasaki Y, Yonetani Y, Iwaki K (1999) Analysis of circadian blood pressure rhythm and target-organ damage in stroke-prone spontaneously hypertensive rats. J Hypertens 17: 211–220 PubMedCrossRefGoogle Scholar
  12. 12.
    Tabuchi M, Umegaki K, Ito T, Suzuki M, Ikeda M, Tomita T (2001) Disturbance of circadian rhythm in heart rate, blood pressure and locomotive activity at the stroke-onset in malignant stroke-prone spontaneously hypertensive rats. Jpn J Pharmacol 85: 197–202 PubMedCrossRefGoogle Scholar
  13. 13.
    Mullins JJ, Peters J, Ganten D (1990) Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature 344: 541–544 PubMedCrossRefGoogle Scholar
  14. 14.
    Witte K, Lemmer B (1999) Development of inverse circadian blood pressure pattern in transgenic hypertensive TGR(mREN2)27 rats. Chronobiol Int 16: 293–303 PubMedCrossRefGoogle Scholar
  15. 15.
    Lemmer B, Witte K, Enzminger H, Schiffer S, Hauptfleisch S (2003) Transgenic TGR(mREN2)27 rats as a model for disturbed circadian organization at the level of the brain, the heart, and the kidneys. Chronobiol Int 20: 711–738 PubMedCrossRefGoogle Scholar
  16. 16.
    Canal-Corretger MM, Witte K, Diez-Noguera A, Lemmer B (2001) Effect of short light–dark cycles on young and adult TGR(mREN2)27 rats. Chronobiol Int 18: 641–656 PubMedCrossRefGoogle Scholar
  17. 17.
    Lemmer B, Hauptfleisch S, Witte K (2000) Loss of 24 h rhythm and light-induced c-fos mRNA expression in the suprachiasmatic nucleus of the transgenic hypertensive TGR(mRen2)27 rat and effects on cardiovascular rhythms. Brain Res 883: 250–257 PubMedCrossRefGoogle Scholar
  18. 18.
    Palkovits M (1973) Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res 59:449–450 PubMedCrossRefGoogle Scholar
  19. 19.
    Palkovits M, Brownstein MJ (1988) Maps and Guide to Microdissection of the Rat Brain. Elsevier Science Publishing Co., New York, pp 1–242Google Scholar
  20. 20.
    Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162: 156–159 PubMedCrossRefGoogle Scholar
  21. 21.
    Nelson W, Tong YL, Lee JK, Halberg F (1979) Methods for cosinor–rhythmometry. Chronobiologia 6: 305–323 PubMedGoogle Scholar
  22. 22.
    Klemfuss H, Clopton PL (1993) Seeking tau: a comparison of six methods. J Interdisciplinary Cycle Res 24: 1–16 Google Scholar
  23. 23.
    Lopez-Molina L, Conquet F, Dubois-Dauphin M, Schibler U (1997) The DBP gene is expressed according to a circadian rhythm in the suprachiasmatic nucleus and influences circadian behavior. EMBO J 16: 6762–6771 PubMedCrossRefGoogle Scholar
  24. 24.
    Honma S, Ikeda M, Abe H, Tanahashi Y, Namihira M, Honma K, Nomura M (1998) Circadian oscillation of BMAL1, a partner of a mammalian clock gene Clock, in rat suprachiasmatic nucleus. Biochem Biophys Res Commun 250: 83–87 PubMedCrossRefGoogle Scholar
  25. 25.
    von Gall C, Noton E, Lee C, Weaver DR (2003) Light does not degrade the constitutively expressed BMAL1 protein in the mouse suprachiasmatic nucleus. Eur J Neurosci 18: 125–133 CrossRefGoogle Scholar
  26. 26.
    Hamada T, LeSauter J, Venuti JM, Silver R (2001) Expression of Period genes: rhythmic and nonrhythmic compartments of the suprachiasmatic nucleus pacemaker. J Neurosci 21: 7742–7750 PubMedGoogle Scholar
  27. 27.
    Hamada T, Antle MC, Silver R (2004) Temporal and spatial expression patterns of canonical clock genes and clock-controlled genes in the suprachiasmatic nucleus. Eur J Neurosci 19: 1741–1748 PubMedCrossRefGoogle Scholar
  28. 28.
    Maywood ES, O’Brien JA, Hastings MH (2003) Expression of mCLOCK and other circadian clock-relevant proteins in the mouse suprachiasmatic nuclei. J Neuroendocrinol 15: 329–334 PubMedCrossRefGoogle Scholar
  29. 29.
    Sano H, Hayashi H, Makino M, Takezawa H, Hirai M, Saito H, Ebihara S (1995) Effects of suprachiasmatic lesions on circadian rhythms of blood pressure, heart rate and locomotor activity in the rat. Jpn Circ J 59: 565–573 PubMedGoogle Scholar
  30. 30.
    Witte K, Schnecko A, Buijs RM, van der Vliet J, Scalbert E, Delagrange P, Guardiola-Lemaitre B, Lemmer B (1998) Effects of SCN lesions on circadian blood pressure rhythm in normotensive and transgenic hypertensive rats. Chronobiol Int 15: 135–145 PubMedCrossRefGoogle Scholar
  31. 31.
    Dampney RA, Polson JW, Potts PD, Hirooka Y, Horiuchi J (2003) Functional organization of brain pathways subserving the baroreceptor reflex: studies in conscious animals using immediate early gene expression. Cell Mol Neurobiol 23: 597–616 PubMedCrossRefGoogle Scholar
  32. 32.
    Dampney RA (1994) Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 74: 323–364 PubMedGoogle Scholar
  33. 33.
    Herichova I, Zeman M, Stebelova K, Ravingerova T (2005) Effect of streptozotocin-induced diabetes on daily expression of per2 and dbp in the heart and liver and melatonin rhythm in the pineal gland of Wistar rat. Mol Cell Biochem 270: 223–229 PubMedCrossRefGoogle Scholar
  34. 34.
    Yamamoto T, Nakahata Y, Soma H, Akashi M, Mamine T, Takumi T (2004) Transcriptional oscillation of canonical clock genes in mouse peripheral tissues. BMC Mol Biol 5:18 PubMedCrossRefGoogle Scholar
  35. 35.
    Young ME, Razeghi P, Taegtmeyer H (2001) Clock genes in the heart: characterization and attenuation with hypertrophy. Circ Res 88: 1142–1150 PubMedGoogle Scholar
  36. 36.
    Mohri T, Emoto N, Nonaka H, Fukuya H, Yagita K, Okamura H, Yokoyama M (2003) Alterations of circadian expressions of clock genes in Dahl salt-sensitive rats fed a high-salt diet. Hypertension 42: 189–194 PubMedCrossRefGoogle Scholar
  37. 37.
    Naito Y, Tsujino T, Kawasaki D, Okumura T, Morimoto S, Masai M, Sakoda T, Fujioka Y, Ohyanagi M, Iwasaki T (2003) Circadian gene expression of clock genes and plasminogen activator inhibitor-1 in heart and aorta of spontaneously hypertensive and Wistar-Kyoto rats. J Hypertens 21: 1107–1115PubMedCrossRefGoogle Scholar
  38. 38.
    Zhao Y, Bader M, Kreutz R, Fernandez-Alfonso M, Zimmermann F, Ganten U, Metzger R, Ganten D, Mullins JJ, Peters J (1993) Ontogenetic regulation of mouse Ren-2d renin gene in transgenic hypertensive rats, TGR(mREN2)27. Am J Physiol 265: E699–707 PubMedGoogle Scholar
  39. 39.
    Jurkovicova D, Kvetnansky R, Krizanova O (1999) Expression of cardiac renin and its modulation by stress in normotensive and hypertensive rats. Gen Physiol Biophys 18: 323–333 PubMedGoogle Scholar
  40. 40.
    Ekker M, Tronik D, Rougeon F (1989) Extra-renal transcription of the renin genes in multiple tissues of mice and rats. Proc Natl Acad Sci USA 86: 5155–5158 PubMedCrossRefGoogle Scholar
  41. 41.
    Johnston CI (1994) Tissue angiotensin converting enzyme in cardiac and vascular hypertrophy, repair, and remodeling. Hypertension 23: 258–268 PubMedGoogle Scholar
  42. 42.
    Allen AM, Moeller I, Jenkins TA, Zhuo J, Aldred GP, Chai SY, Mendelsohn FA (1998) Angiotensin receptors in the nervous system. Brain Res Bull 47: 17–28 PubMedCrossRefGoogle Scholar
  43. 43.
    Gasc JM, Shanmugam S, Sibony M, Corvol P (1994) Tissue-specific expression of type 1 angiotensin II receptor subtypes. An in situ hybridization study. Hypertension 24: 531–537 PubMedGoogle Scholar
  44. 44.
    Schiffer S, Pummer S, Witte K, Lemmer B (2001) Cardiovascular regulation in TGR(mREN2)27 rats: 24 h variation in plasma catecholamines, angiotensin peptides, and telemetric heart rate variability. Chronobiol Int 18: 461–474PubMedCrossRefGoogle Scholar
  45. 45.
    Kopkan L, Kramer HJ, Huskova Z, Vanourkova Z, Skaroupkova P, Thurmova M, Cervenka L (2005) The role of intrarenal angiotensin II in the development of hypertension in Ren-2 transgenic rats. J Hypertens 23: 1531–1539 PubMedCrossRefGoogle Scholar
  46. 46.
    Baltatu O, Janssen BJ, Bricca G, Plehm R, Monti J, Ganten D, Bader M (2001) Alterations in blood pressure and heart rate variability in transgenic rats with low brain angiotensinogen. Hypertension 37: 408–413 PubMedGoogle Scholar
  47. 47.
    Campos LA, Iliescu R, Baltatu O, Bader M: Hypertonie 2003: 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga (2003), Bonn, pp. Doc03hochV16Google Scholar
  48. 48.
    da Silva Lemos M, Nardoni Goncalves Braga A, Roberto da Silva J, Augusto Souza Dos Santos R (2005) Altered cardiovascular responses to chronic angiotensin II infusion in aged rats. Regul Pept 132: 67–73 PubMedCrossRefGoogle Scholar
  49. 49.
    Nonaka H, Emoto N, Ikeda K, Fukuya H, Rohman MS, Raharjo SB, Yagita K, Okamura H, Yokoyama M (2001) Angiotensin II induces circadian gene expression of clock genes in cultured vascular smooth muscle cells. Circulation 104: 1746–1748 PubMedGoogle Scholar
  50. 50.
    Cugini P, Lucia P (2004) Circadian rhythm of the renin–angiotensin-aldosterone system: a summary of our research studies. Clin Ter 155: 287–291 PubMedGoogle Scholar
  51. 51.
    Kaschina E, Unger T (2003) Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press 12: 70–88 PubMedCrossRefGoogle Scholar

Copyright information

© Springer Science+Business Media, Inc. 2006

Authors and Affiliations

  • Iveta Herichová
    • 1
  • Boris Mravec
    • 2
    • 3
  • Katarína Stebelová
    • 1
  • Ol’ga Križanová
    • 4
  • Dana Jurkovičová
    • 4
  • Richard Kvetňanský
    • 3
  • Michal Zeman
    • 1
  1. 1.Department of Animal Physiology and EthologyComenius University BratislavaBratislavaSlovak Republic
  2. 2.Institute of Pathophysiology, Faculty of MedicineComenius UniversityBratislavaSlovak Republic
  3. 3.Institute of Experimental EndocrinologySlovak Academy of SciencesBratislavaSlovak Republic
  4. 4.Institute of Molecular Physiology and GeneticsSlovak Academy of SciencesBratislavaSlovak Republic

Personalised recommendations