Protective effects of rutaecarpine in cardiac anaphylactic injury is mediated by CGRP.
Previous investigations have indicated that rutaecarpine activates the vanilloid receptor to evoke calcitonin gene-related peptide (CGRP) release. CGRP has been shown to alleviate cardiac anaphylactic injury. In the present study, the effect of rutaecarpine on cardiac anaphylaxis was examined. Challenge of presensitized guinea-pig hearts with a specific antigen caused marked decreases in coronary flow (CF), left ventricular pressure (LVP) and its derivatives (+/- dp/dt(max)), an increase in heart rate, and prolongation of the P-R interval. Rutaecarpine (0.3 or 1 microM) markedly increased the content of calcitonin gene-related peptide (CGRP) in the coronary effluent and decreased the content of tumor necrosis factor-alpha (TNF-alpha) in myocardial tissues concomitantly with a significant improvement of cardiac function and alleviation of the extension of the P-R interval. Rutaecarpine at the concentration of 1 microM also inhibited the sinus tachycardia. The protective effects of rutaecarpine on cardiac anaphylaxis were abolished by CGRP (8-37), a selective CGRP receptor antagonist. These results suggest that the protective effects of rutaecarpine on cardiac anaphylactic injury are related to inhibition of TNF-alpha production by stimulation of CGRP release.
Yi
Hong-Hui
HH
Department of Pharmacology, School of Pharmaceutical Sciences, Central South University, Changsha, Hunan, P. R. China.
Rang
Wei-Qing
WQ
Deng
Pan-Yue
PY
Hu
Chang-Ping
CP
Liu
Gui-Zhen
GZ
Tan
Gui-Shan
GS
Xu
Kang-Ping
KP
Li
Yuan-Jian
YJ
D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D000707:Anaphylaxis / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D001794:Blood Pressure; D002316:Cardiotonic Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D003331:Coronary Vessels / Q000503:physiopathology; D032086:Evodia; D005260:Female; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate; D026121:Indole Alkaloids; D008297:Male; D009206:Myocardium / Q000378:metabolism; D008517:Phytotherapy; D011799:Quinazolines; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D052999:Quinazolinones
D000470:Alkaloids; D002316:Cardiotonic Agents; D026121:Indole Alkaloids; D011799:Quinazolines; D014409:Tumor Necrosis Factor-alpha; C028632:rutecarpine; D052999:Quinazolinones