Disruption of Circadian Gene Expression in Skeletal Muscle but not Liver in Pre-Hypertensive SHR Vs. WKY Rats

Recently, alterations of the molecular clock and circadian rhythms have been implicated as contributing factors to cardiovascular and skeletal muscle disease. Woon et al. (2007) determined that a polymorphism found in the congenic interval of the SHR rat is associated with hypertension and type II diabetes. Here, we examined the expression of circadian genes in striated muscle (cardiac and skeletal muscle) in young pre-hypertensive SHR (6 weeks old) and age-matched Wistar-Kyoto (WKY) male rats. The rats were entrained to a 12 hour light: 12 hour dark cycle for 2 weeks and then placed in constant darkness for 30 hours. Cardiac muscle (left ventricle), skeletal muscle (soleus) and non-muscle tissue (liver) were collected every 4 hours for 40 hrs, totally 10 time points. Expression of core clock genes (Bmal1, Clock, Per2, Rorα, Rev-erb) and the clock-controlled gene, Dbp, were analyzed using real-time quantitative PCR. Expression of Bmal1 has a clear circadian pattern in muscle and liver tissue of rats. The pattern and amplitude of circadian expression of Bmal1 were not altered between WKY and SHR strains in every tissue studied. In contrast, expression of the other clock genes, Rorα, Dbp, Rev-erb, Clock and Per2, were significantly dys-regulated in the soleus muscle from the SHR rat. In the left ventricle, circadian expression of Per2 was dampened in the SHR but the other clock genes were unchanged. In liver, there were no differences in expression of any of the clock genes between the SHR and WKY rats. These data suggest that components of the molecular clock are disrupted in striated muscle prior to overt signs of hypertension. The contribution of this disruption in the clock to hypertension and type II diabetes are to be determined.