Reversal of isoprenaline-induced cardiac remodeling by rutaecarpine via stimulation of calcitonin gene-related peptide production.
Dysfunction of capsaicin-sensitive sensory nerves is involved in cardiac remodeling, and rutaecarpine has been shown to exert a beneficial effect on cardiac function through activating the sensory nerves. This study was conducted to explore the potential inhibitory effect of rutaecarpine on cardiac remodeling and the underlying mechanisms. A rat cardiac remodeling model was established by injection of isoprenaline (5 mg/kg per day, s.c.) for 10 days. Rutaecarpine (10 or 40 mg/kg, i.g.) was coadministrated with isoprenaline to evaluate the effect of rutaecarpine on cardiac remodeling. After echocardiographic analysis was performed, blood samples were collected to quantify calcitonin gene-related peptide (CGRP), dorsal root ganglia were isolated for examining CGRP mRNA expression, and the hearts were weighed and saved for evaluating the parameters related to apoptosis and hypertrophy. Isoprenaline significantly increased the ratio of left ventricle weight to body weight, the cross-sectional area of cardiomyocytes, cardiac apoptosis, and collagen deposition concomitantly with decreased CGRP production, which were reversed by rutaecarpine treatment. The beneficial effects of rutaecarpine were attenuated by pretreatment with capsaicin, which selectively depleted CGRP. These results suggest that rutaecarpine was able to reverse isoprenaline-induced cardiac remodeling through stimulating CGRP production.
Li
Jian-Zhe
JZ
Department of Pharmacology, Central South University, Changsha, China.
Peng
Jun
J
Xiao
Li
L
Zhang
Yi-Shuai
YS
Liao
Mei-Chun
MC
Li
Xiao-Hui
XH
Hu
Chang-Ping
CP
Deng
Han-Wu
HW
Li
Yuan-Jian
YJ
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001835:Body Weight / Q000187:drug effects; D015740:Calcitonin Gene-Related Peptide / Q000096:biosynthesis* / Q000097:blood; D004452:Echocardiography; D005727:Ganglia, Spinal / Q000378:metabolism; D006352:Heart Ventricles / Q000187:drug effects* / Q000294:innervation; D020287:In Situ Nick-End Labeling; D026121:Indole Alkaloids / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D008297:Male; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011799:Quinazolines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020257:Ventricular Remodeling / Q000187:drug effects*; D052999:Quinazolinones
D015740:Calcitonin Gene-Related Peptide; D026121:Indole Alkaloids; D007545:Isoproterenol; D011799:Quinazolines; C028632:rutecarpine; D052999:Quinazolinones