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

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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.

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References

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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: 810–813

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  9. Takahashi JS (2004) Finding new Clock components: past and future. J Biol Rhythms 19: 339–347

    Article  PubMed  CAS  Google Scholar 

  10. Lemmer B, Mattes A, Bohm M, Ganten D (1993) Circadian blood pressure variation in transgenic hypertensive rats. Hypertension 22: 97–101

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  13. Mullins JJ, Peters J, Ganten D (1990) Fulminant hypertension in transgenic rats harbouring the mouse Ren-2 gene. Nature 344: 541–544

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  18. Palkovits M (1973) Isolated removal of hypothalamic or other brain nuclei of the rat. Brain Res 59:449–450

    Article  PubMed  CAS  Google Scholar 

  19. Palkovits M, Brownstein MJ (1988) Maps and Guide to Microdissection of the Rat Brain. Elsevier Science Publishing Co., New York, pp 1–242

    Google Scholar 

  20. Chomczynski P, Sacchi N (1987) Single-step method of RNA isolation by acid guanidinium thiocyanate–phenol–chloroform extraction. Anal Biochem 162: 156–159

    Article  PubMed  CAS  Google Scholar 

  21. Nelson W, Tong YL, Lee JK, Halberg F (1979) Methods for cosinor–rhythmometry. Chronobiologia 6: 305–323

    PubMed  CAS  Google Scholar 

  22. Klemfuss H, Clopton PL (1993) Seeking tau: a comparison of six methods. J Interdisciplinary Cycle Res 24: 1–16

    Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  32. Dampney RA (1994) Functional organization of central pathways regulating the cardiovascular system. Physiol Rev 74: 323–364

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  35. Young ME, Razeghi P, Taegtmeyer H (2001) Clock genes in the heart: characterization and attenuation with hypertrophy. Circ Res 88: 1142–1150

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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: 1107–1115

    Article  PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  41. Johnston CI (1994) Tissue angiotensin converting enzyme in cardiac and vascular hypertrophy, repair, and remodeling. Hypertension 23: 258–268

    PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  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: 461–474

    Article  PubMed  CAS  Google Scholar 

  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

    Article  PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  47. Campos LA, Iliescu R, Baltatu O, Bader M: Hypertonie 2003: 27. Wissenschaftlicher Kongress der Deutschen Hochdruckliga (2003), Bonn, pp. Doc03hochV16

  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

    Article  PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  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

    PubMed  CAS  Google Scholar 

  51. Kaschina E, Unger T (2003) Angiotensin AT1/AT2 receptors: regulation, signalling and function. Blood Press 12: 70–88

    Article  PubMed  CAS  Google Scholar 

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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.

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Correspondence to Michal Zeman.

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Herichová, I., Mravec, B., Stebelová, K. et al. Rhythmic clock gene expression in heart, kidney and some brain nuclei involved in blood pressure control in hypertensive TGR(mREN-2)27 rats. Mol Cell Biochem 296, 25–34 (2007). https://doi.org/10.1007/s11010-006-9294-4

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