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. 2007 Feb;296(1-2):25-34. doi: 10.1007/s11010-006-9294-4. Epub 2006 Aug 15.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ARNTL Transcription Factors
  • Animals
  • Basic Helix-Loop-Helix Transcription Factors / genetics
  • Basic Helix-Loop-Helix Transcription Factors / metabolism
  • Biological Clocks / genetics*
  • Blood Pressure / physiology*
  • CLOCK Proteins
  • Cell Cycle Proteins / genetics
  • Cell Cycle Proteins / metabolism
  • Circadian Rhythm / physiology
  • DNA-Binding Proteins / genetics
  • DNA-Binding Proteins / metabolism
  • Gene Expression Regulation / physiology*
  • Heart / physiology*
  • Kidney / physiology*
  • Male
  • Medulla Oblongata / anatomy & histology
  • Medulla Oblongata / physiology
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism
  • Period Circadian Proteins
  • Rats
  • Rats, Inbred SHR
  • Rats, Inbred Strains*
  • Rats, Sprague-Dawley
  • Renin-Angiotensin System / physiology
  • Solitary Nucleus / cytology
  • Solitary Nucleus / physiology
  • Suprachiasmatic Nucleus / cytology
  • Suprachiasmatic Nucleus / physiology
  • Trans-Activators / genetics
  • Trans-Activators / metabolism
  • Transcription Factors / genetics
  • Transcription Factors / metabolism

Substances

  • ARNTL Transcription Factors
  • Basic Helix-Loop-Helix Transcription Factors
  • Cell Cycle Proteins
  • DBP protein, rat
  • DNA-Binding Proteins
  • Nuclear Proteins
  • Per2 protein, rat
  • Period Circadian Proteins
  • Trans-Activators
  • Transcription Factors
  • CLOCK Proteins
  • Clock protein, rat