ENDOTHELIN SYSTEM mRNA VARIATION IN THE HEART OF ZUCKER RATS: EVALUATION OF A POSSIBLE BALANCE WITH NATRIURETIC PEPTIDES

Background: The deregulation of neurohormonal systems, including the natriuretic peptide (NP) and endothelin (ET) systems, may increase the possibility of developing obesity-related risk. The aim of our paper was to evaluate ET system mRNA variation in heart of the Zucker rat model together with the simultaneous evaluation of the NP system transcriptomic profile. In order to analyze the link between the ET-1 system and the inflammatory process, the cardiac expression of interleukin (IL)-6 and tumor necrosis factor (TNF)-? was also measured. Methods and Results: Zucker rats of 9-13 weeks were subdivided into obese rats (O, n=20), and controls (CO, n=20): half of them were studied under fasting conditions (CO fc -O fc ) and the remainder after the induction of acute hyperglycemia (CO AH -O AH ). Cardiac mRNA expression of TNF-?, IL-6, NP/ET-1 systems was evaluated by Real Time-PCR. No significant difference for pre-proET-1, ET-A and ET-B mRNA expression was detected between O and CO, whereas significantly lower mRNA levels of the ECE-1 were observed in O (p=0.02). Regarding NPs, only BNP mRNA expression decreased significantly in O with respect to CO (p=0.01). A down-regulation of NPR-B and NPR-C and an up-regulation of NPR-A was observed in O. No significant difference for IL-6 and TNF-? mRNA was revealed. Subdividing into fasting and hyperglycemic rats, many of the genes studied maintained their mRNA expression pattern almost unchanged. Conclusions: The modulation of ET-1/NP systems in obesity could be a useful starting point for future studies aimed at identifying new therapeutic strategies for the treatment of cardiometabolic syndrome.