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

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.

Clock Genes Display Rhythmic Expression in Human Hearts

“…As stated earlier, myocardial clock genes and their rhythms had previously been researched only in mice Herichova et al, 2007;Storch et al, 2002;Young et al, 2001). Storch et al (2002) described the acrophase of the PER1 and PER2 circadian FIGURE 4 Relative quantity, sliding means, and cosinor function of BMAL1 in the human myocardium.…”

“…The fact that we found rhythms of PER mRNA almost exactly in antiphase to BMAL1 mRNA additionally confirms our results. Furthermore, it has been demonstrated that alterations in PER1 and PER2 circadian rhythms are associated with not only various cellular pathology (e.g., some cancers: Chen et al, 2005;Gery et al, 2006Gery et al, , 2007Krugluger et al, 2007;Lee, 2006;Winter et al, 2007) but also with hypertension (Herichova et al, 2007) and myocardial hypertrophy (Young et al, 2001). Thus, Per genes seem to be of special relevance for cellular functionality also in the heart.…”

“…These "clock genes" have been found to control 8 -10% of the genes expressed in each tissue in a distinct way (Albrecht, 2002;Balsalobre et al, 1998;Konopka & Benzer, 1971;Storch et al, 2002). The expression of clock genes has been reported in a number of tissues (Abe et al, 2002;Balsalobre et al, 1998;Chen-Goodspeed & Lee, 2007), including the myocardium (Herichova et al, 2007;Young et al, 2001). Consequently, cardiac clock genes have been associated with distinct 24 h variation in the myocardial oxidative and non-oxidative metabolism of carbohydrates and lipids .…”

Disrupted circadian rhythm in rats with nephrectomy-induced chronic kidney disease

“…e l s e v i e r . c o m / l o c a t e / l i f e s c i e the homeostatic functions of the peripheral organs, including heart and kidney (Herichova et al, 2007). The circadian rhythm of clock gene expression may be modified to some extent between peripheral tissues, as denoted by differences in amplitude and phasing, and operates differently .…”

“…This phenomenon could be partially explained by the variation of circadian blood pressure (Elung-Jensen et al, 2008). Modified circadian gene expression both centrally and peripherally has been shown in an animal model of hypertensive rats (Herichova et al, 2007). Treatment of CKD from chronobiological points of view might be beneficial to patients with early CKD.…”