CGRP inhibits norepinephrine induced apoptosis with restoration of Bcl-2/Bax in cultured cardiomyocytes of rat

• Norepinephrine increases apoptosis of cardiomyocytes.
• Norepinephrine increases Bax and reduces Bcl-2 and ratio of Bcl-2/Bax.
• CGRP increases Bcl-2 and ratio of Bcl-2/Bax in cardiomyocytes.
• CGRP attenuates norepinephrine induced apoptosis of cardiomyocytes.

Calcitonin gene related peptide (CGRP) and norepinephrine (NE) may interact in acute myocardial ischemia, protecting cardiomyocytes but the underlying mechanism is unclear. Here we investigated the correlation of the anti-apoptotic effect of CGRP with the change of Bcl-2/Bax. Cultured cardiomyocytes were divided into four groups: (1) control group (no treatment with any test agent), (2) NE group (treated with 10−5 mol/L of NE), (3) CGRP + NE group (treated with 10−8 mol/L of CGRP and NE at 10−5 mol/L) and (4) CGRP8-37 + CGRP + NE group (treated with 10−7 mol/L of CGRP8-37, a specific antagonist of CGRP receptor, CGRP at 10−8 mol/L and NE at 10−5 mol/L). Apoptosis ratio was analyzed by flow cytometry. Bcl-2 and Bax and the coding mRNA were examined. It was found that the apoptosis ratio in NE group (29.4 ± 1.8%) was significantly greater (P < 0.05) than that of the control group (10.1 ± 1.7%). The effect of NE was attenuated by CGRP (18.7 ± 2.1%), which was reversed by CGRP8-37 (24.9 ± 2.9%). NE treatment resulted in reductions in the ratio of Bcl-2/Bax (by 33%) and their mRNA (by 53%). CGRP restored the level of Bcl-2/Bax, which was abolished by CGRP8-37. Current study suggests that norepinephrine inhibits synthesis of Bcl-2 and increases Bax and apoptosis of cardiomyocytes. CGRP restores the ratio of Bcl-2/Bax and attenuates the apoptosis induced by NE, via specific CGRP receptor.