Cardiometabolic Parameters and Transcription Factors in Rat Models of Prehypertension With or Without Hypertriglyceridemia: Focus on NRF2 and PPARα Gene Expression

This study investigated selected cardiovascular, hepatic, and metabolic parameters, including Nfe2l2, Hmox1 (an NRF2 target gene), and Ppara gene expression, in adult male normotensive Wistar-Kyoto (WKY), borderline hypertensive (BHR) and hereditary hypertriglyceridemic (HTG) rats. BHR and HTG rats exhibited increased blood pressure vs. WKY, but there were no differences in blood pressure of BHR and HTG rats. In contrast, HTG had elevated hematocrit, triacylglycerol levels, glycemia and atherogenic index of plasma, and decreased total cholesterol and HDL-cholesterol compared to BHR rats. In addition, nitric oxide synthase activity in the heart and liver was significantly reduced in HTG vs. BHR. Gene expressions of Nfe2l2, Ppara, and Hmox1 were significantly elevated in the hearts of HTG rats compared to both WKY and BHR. In contrast, hepatic expression levels of Nfe2l2 and Hmox1 were significantly reduced in BHR and HTG compared to WKY, while Ppara expression in the liver was significantly reduced in HTG vs. both BHR and WKY. Vascular studies revealed that endothelium-dependent relaxation was reduced in HTG rats vs. BHR, suggesting a dominant effect of hypertriglyceridemia, while endothelium-independent relaxation was reduced in both HTG and BHR rats vs. WKY, suggesting a dominant effect of prehypertension in this vascular bed. Contraction responses were also more pronounced in HTG rats vs. BHR. Overall, this study showed that inherited hypertriglyceridemia (combined with prehypertension) alters vascular function and redox–metabolic balance in a tissue-dependent manner and represents a more significant cardiometabolic risk in later periods of life than prehypertension itself.