Nebivolol alters the expression of pro‐fibrosis microRNAs in Dahl Salt sensitive rats

Background MicroRNAs (miRNAs) are small (~22 nt) noncoding single‐stranded RNA molecules that downregulate gene expression. Studies have shown that miRNAs control diverse aspects of heart disease, including hypertrophy, remodeling, heart failure, and arrhythmia. Purpose To assess the effects of Nebivolol (Neb), a new β‐blocker drug with nitric oxide enhancing and anti‐inflammatory effects, on the cardiac expression of miRNAs in a model of salt‐sensitive hypertension. Methods Six‐week old Dahl Salt Sensitive (SS/JrHsdMcwiCrl) rats received either normal chow (control) or AIN‐76A high‐salt (HS)(8% NaCl) diet for 8 weeks. At 4 weeks the high‐salt fed rats were randomized to Neb (10 mg/kg/d) or vehicle for 4 weeks, administered by Alzet osmotic pump. Hearts were harvested, mRNA was extracted and sent to L.C. Sciences (Houston, TX) for microRNA‐microarray. Results were confirmed by qRT‐PCR. Results HS diet induced hypertension. Neb attenuated this increase. HS diet increased the expression of miR‐21 and miR 146a and decreased the expression of miR30c, miR499 and miR27a (Table). Neb reversed the effects of HS diet and significantly increased miR499 and miR27a above control. Conclusions MiR21 and miR30c are known to control myocardial fibrosis. MiR21 is associated with left ventricular hypertrophy. HS diet alters the expression of a set of miRNAs, including these two pro‐fibrosis miRNAs. Neb reversed the HS‐induced changes in blood pressure and miRNA expression.