Assessment of mitochondrial DNA polymorphisms in salt-sensitive hypertension in Dahl salt-sensitive rats

Abstract

The Dahl salt-sensitive (DS) rat is the most prevalently used animal model of salt-sensitive hypertension. The purpose of the present study was to test the hypothesis that mitochondrial DNA (mtDNA) polymorphisms influence blood pressure in DS rats. We produced two strains of female F1 rats, one from female DS and male Lewis rats (DL) and the other from Lewis female and DS male rats (LD). These two strains had the same autosomal genetic background, but their mitochondria had different origins. The DL and LD rats had DS and Lewis mitochondria, respectively. A high-salt diet was started at 4 weeks of age. Radiotelemetry devices were implanted into the lower abdominal aorta of these F1 rats at 9 weeks of age. Blood pressure was monitored for 24 h at 11, 12, 13, 14, and 19 weeks of age. No significant differences were observed in blood pressure levels between the strains. Although more than 100 polymorphisms were detected between DS and Lewis rats, it is unlikely that polymorphisms in mtDNA contribute to hypertension in DS rats. Moreover, we found no difference between DS and Lewis rats in the mtDNA copy number in the kidneys, the liver, and the ventricles of the heart before and after salt loading. Thus, it is unlikely that mitochondrial dysfunction due to high blood pressure exacerbated target organ damage. Intriguingly, the time course of body weight gain differed significantly between DL and LD F1 rats, suggesting the influence of mitochondrial polymorphisms on body composition.