Objective: 

Both calcitonin gene-related peptide (CGRP) and adrenomedullin (AM) regulates vascular tone in the heart, being cardioprotective in hypoxia. Additionally CGRP exerts positive inotropic and chronotropic effect, while AM exhibit antiproliferative and antiapoptotic functions in the myocardium. Their actions are mediated through specific G protein-coupled receptors, calcitonin receptor-like receptor (CRLR), respectively. Ligand affinity of CRLR is determined by receptor activity modifying proteins (RAMP1-3). CGRP binds to the complex formed by CRLR/RAMP1, whereas CRLR/RAMP2 and CRLR/RAMP3 serve as receptors for ADM. Here, we investigated this signalling systems in the control rat heart and compared it to that in diabetic rats.

Methods: 

The separated rat heart compartments from animals 8 weeks after administration of streptozotocin (STZ; 65 mg/kg i.v) and in the age-matched controls (n=6 per group) were analyzed by real-time RT-PCR. Relative expression of AM, CGRP, CRLR, RAMP1-3 mRNA was expressed as a ratio of target gene Cq value to Cq value of reference gene – beta-actin. The results were considered significantly different when p<0.05.

Results: 

We have observed some changes in relative expression of the genes just in right heart compartments. In the right atrium AM expression declined to 50% of controls, while in the right ventricle RAMP1 was strongly upregulated. Relative expressions of other tested genes were not significantly altered.

Conclusions: 

In summary, the shifts observed in short-term diabetes may favour a trend of a pronounced CGRP signalling. These observations may provide a new possible therapeutic strategy for diabetic cardiomyopathy.

Granted by GAUK 99510 and DFG, 436 TSE 113/51/0-1.