Increase in cardiac P2X1- and P2Y2-receptor mRNA levels in congestive heart failure

We wanted to study the expression of P2-receptors at the mRNA-level in the heart and if it is affected by congestive heart failure (CHF). To quantify the P2 receptor mRNA-expression we used a competitive RT-PCR protocol which is based on an internal RNA standard. The P2 receptor mRNA-expression was quantified in hearts from CHF rats and compared to sham-operated rats. Furthermore, the presence of receptor mRNA was studied in the myocardium from patients with heart failure. In the sham operated rats the G-protein coupled P2Y-receptors were expressed at a higher level than the ligand gated ion-channel receptor (P2X(1)). Among the P2Y-receptors the P2Y(6)-receptor was most abundantly expressed (P2Y(6) > P2Y(1) > P2Y(2) = P2Y(4) > P2X(1)). A prominent change was seen for the P2X(1)- and P2Y(2)-receptor mRNA levels which were increased 2.7-fold and 4.7-fold respectively in the myocardium from the left ventricle of CHF-rats. In contrast, the P2Y(1)-, P2Y(4)- and P2Y(6)-receptor mRNA levels were not significantly altered in CHF rats. In human myocard the P2X(1)-, P2Y1-, P2Y(2)-, P2Y(6)- and P2Y(11)-receptors were detected by RT-PCR in both right and left atria and ventricles, while the P2Y(4)-receptor band was weak or absent. In conclusion, most of the studied P2-receptors were expressed in both rat and human hearts. Furthermore, the P2X1- and P2Y(2)-receptor mRNA were upregulated in CHF, suggesting a pathophysiological role for these receptors in the development of heart failure.