Involvement of alpha-calcitonin gene-related peptide in heat stress-induced delayed preconditioning in rat hearts.
1. Previous studies have shown that hyperthermia is capable of activating capsaicin-sensitive sensory nerves and stimulating the release of neurotransmitters from their peripheral terminals. Calcitonin gene-related peptide (CGRP) has recently been found to participate in delayed cardioprotection in rat isolated hearts. 2. The purpose of the present study was to explore whether the delayed cardioprotection by heat stress in vivo involves the expression and release of CGRP. 3. Sprague-Dawley rats were pretreated with whole-body hyperthermia (rectal 42 degrees C) for 15 min, 24 h before the experiments and then the left main coronary artery of rat hearts was subjected to a 45 min occlusion followed by 3 h reperfusion. The degree of myocardial injury was evaluated by measurement of infarct size and plasma creatine kinase (CK) activity. The plasma levels of CGRP and expression of CGRP (alpha and beta isoforms) mRNA in lumbar dorsal root ganglia at 4, 8, 16 or 24 h after heat stress treatment were measured. 4. Pretreatment with hyperthermia significantly reduced infarct size and CK release. Heat stress also significantly increased plasma concentrations of CGRP and the expression of alpha-CGRP mRNA, but not beta-CGRP mRNA. The effect of heat stress was completely abolished by pretreatment with capsaicin (50 mg/kg, s.c.), which selectively depletes transmitters in capsaicin-sensitive sensory nerves. 5. In summary, the results suggest that the delayed cardioprotection by heat stress involves the synthesis and release of CGRP and that the protection is mainly mediated by the alpha-CGRP isoform.
Peng
Jun
J
Department of Pharmacology, Xiang-Ya Medical College, Central South University, Changsha, Hunan, People's Republic of China.
Lu
Rong
R
Xiao
Liang
L
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000097:blood; D002211:Capsaicin / Q000494:pharmacology; D003402:Creatine Kinase / Q000097:blood; D005727:Ganglia, Spinal / Q000378:metabolism / Q000503:physiopathology; D018882:Heat Stress Disorders / Q000378:metabolism* / Q000503:physiopathology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D009203:Myocardial Infarction / Q000097:blood / Q000378:metabolism*; D015425:Myocardial Reperfusion; D020033:Protein Isoforms / Q000096:biosynthesis / Q000097:blood; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction
D020033:Protein Isoforms; D012333:RNA, Messenger; D003402:Creatine Kinase; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin