Role of calcitonin gene-related peptide in prostaglandins-mediated ischemic preconditioning in guinea pig hearts.
OBJECTIVE
To examine the role of calcitonin gene-related peptide (CGRP) in ischemic preconditioning induced by prostaglandins in isolated guinea pig hearts.


METHODS
The isolated guinea pig hearts were perfused in a Langendorff model. The heart rate, coronary flow, left ventricular pressure, and its first derivatives (+/-dp/dt(max)) were recorded and the calcitonin gene-related peptide-like immunoreactivity (CGRP-LI) and 6-keto-PGF(1 alpha) were measured.


RESULTS
Endothelin-1 (200 pmol in 1 mL K-H buffer) reduced the left ventricular developed pressure and its first derivatives (+/-dp/dt(max)), heart rate, and coronary flow. Preconditioning with two cycles of 5-min global ischemia and 5-min reperfusion attenuated endothelin-1 induced myocardial injury, and concentrations of both CGRP and 6-keto-PGF(1alpha) in the coronary effluent were markedly raised in the preconditioning periods. Pretreatment with capsaicin, which depletes endogenous CGRP, abolished the elevated level of CGRP concomitantly with loss of the cardioprotection induced by ischemic preconditioning. CGRP(8-37) (100 nmol/L), a selective CGRP1 receptor antagonist, also abolished the protective effects of ischemic preconditioning. After pretreatment with indometacin (10 micromol/L), an inhibitor of cyclooxygenase, the protective effects of ischemic preconditioning were abolished and the release of 6-keto-PGF1alpha was no longer elevated. Pretreatment with indometacin abolished the elevated level of CGRP in the coronary effluent.


CONCLUSIONS
Endogenous prostaglandins are involved in the protective effects of ischemic preconditioning, and the beneficial effects of prostaglandins are mediated by CGRP in the guinea pig heart.
Song
Q J
QJ
Department of Pharmacology, Hunan Medical University, Changsha 410078, China.
Xiao
J
J
Deng
H W
HW
Li
Y J
YJ
D015121:6-Ketoprostaglandin F1 alpha / Q000502:physiology*; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism / Q000494:pharmacology / Q000502:physiology*; D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D002211:Capsaicin / Q000494:pharmacology; D003326:Coronary Circulation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D019332:Endothelin-1 / Q000378:metabolism; D006168:Guinea Pigs; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007213:Indomethacin / Q000494:pharmacology; D019157:Ischemic Preconditioning, Myocardial; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control; D010446:Peptide Fragments / Q000494:pharmacology; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use
D000077221:Calcitonin Gene-Related Peptide Receptor Antagonists; D016861:Cyclooxygenase Inhibitors; D019332:Endothelin-1; D010446:Peptide Fragments; D020011:Protective Agents; C058636:calcitonin gene-related peptide (8-37); D015121:6-Ketoprostaglandin F1 alpha; D015740:Calcitonin Gene-Related Peptide; D002211:Capsaicin; D007213:Indomethacin