Effects of calcitonin gene-related peptide and BIBN4096BS on myocardial ischemia in anesthetized rats.
OBJECTIVE
The cardioprotective effect of calcitonin gene-related peptide (CGRP) was investigated in an ischemia rat model.


METHODS
Ischemia-reperfusion injury was provoked by 60 min left main coronary artery occlusion followed by 60 min of reperfusion in anesthetized rats. The transverse slices of ventricles were stained by 2,3,5-triphenyltetrazolium chloride to determine the infarct area. Plasma creatine phosphokinase levels were determined by means of a creatine phosphokinase (CPK) kit. A radioimmunoassay was used to determine plasma CGRP levels.


RESULTS
Intravenous infusion of CGRP (1 nmol . kg-1 . h-1) 10 min before occlusion until the end of reperfusion reduced infarct size by 89 %+/- 5 %. The reduction in infarct size was accompanied by a decrease in circulating levels of creatine phosphokinase. Infusion of the same dose of CGRP commencing from the start of reperfusion until its end induced a 40 % +/- 3 % reduction of the infarct size. The cardioprotective effects of CGRP were blocked by the novel CG RP antagonist BIBN4096BS (20 nmol . kg-1 . h-1). Although cardiac ischemia resulted in an almost 50 % increase in plasma CGRP levels in blood sampled from right cardiac ventricle, intravenous infusion of the CGRP antagonist BIBN4096BS before occlusion until the end of reperfusion had no statistically significant effect on the infarct size.


CONCLUSIONS
The present study demonstrates that CGRP is a potent myocardial protective substance.
Wu
D M
DM
Cardiovascular Research, Boehringer Ingelheim Pharma KG, Birkendorfer Str 65, D-88397 Biberach, Germany.
van Zwieten
P A
PA
Doods
H N
HN
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000037:antagonists & inhibitors / Q000097:blood / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology; D003402:Creatine Kinase / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000201:enzymology / Q000473:pathology*; D015428:Myocardial Reperfusion Injury / Q000201:enzymology / Q000473:pathology*; D010879:Piperazines; D010880:Piperidines / Q000494:pharmacology*; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar
D002316:Cardiotonic Agents; D010879:Piperazines; D010880:Piperidines; D011799:Quinazolines; D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide; C406305:olcegepant