Objectives: 

The cardiac sensory nervous system is responsible for pain perception and for initiating a protective cardiovascular response during myocardial ischemia that is frequent complication of diabetes mellitus. Here, we investigated the effect of long term streptozotocin (STZ) diabetes on the expression of members of the calcitonin/calcitonin gene-related peptide (CGRP) family. Peptides as adrenomedullin (AM), intermedin (IM) and CGRP share the system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP). The CRLR/RAMP2 or CRLR/RAMP3 complex forms the AM receptor, whereas the CRLR/RAMP1 forms the CGRP receptor. Both CGRP and AM regulates vascular tone in the heart. Additionally, ADM exhibit cardioprotective functions.

Materials: 

Diabetes mellitus was induced by a single application of STZ. Expressions of AM, IM, CGRP, CRLR, RAMP1-3 in heart compartments and sensory ganglia were assessed 26 weeks thereafter. Relative expression of mRNA was expressed as a ratio of target gene Cq value to Cq value of reference gene. The results were considered significantly different when p<0.05.

Results: 

In control heart atria, real-time PCR revealed a rank order of expression of RAMP2>AM=CRLR>RAMP1=RAMP3>IM=CGRP, while in the ventricles RAMP2=CRLR=AM>RAMP1=RAMP3>IM=CGRP. In course of STZ diabetes, moderate upregulation of CRLR expression were seen in the left atrium and significant substantial overexpression of RAMP3 in the left ventricle, while other genes remained unchanged in all heart compartments. In the nodose ganglion, a small significant increase in CGRP expression was also observed.

Conclusions: 

Upregulation of RAMP3 would allow AM to exert its beneficial action on the heart affected by diabetic cardiomyopathy in higher extend. Persistence or even upregulation of receptor system would give an opportunity for possible pharmacological intervention.

Granted by GAUK 99510.