CNP infusion attenuates cardiac dysfunction and inflammation in myocarditis.
Myocarditis is an acute inflammatory disease of the myocardium for which there is currently no specific therapy. We investigated the therapeutic potential of C-type natriuretic peptide (CNP) in acute experimental autoimmune myocarditis. One week after injection of porcine myosin into male Lewis rats, CNP (0.05 microg/kg/min) was continuously administered for 2 weeks. CNP infusion significantly increased maximum dP/dt, decreased left ventricular end-diastolic pressure, and improved fractional shortening compared with vehicle administration. In vehicle-treated hearts, severe necrosis and marked infiltration of CD68-positive inflammatory cells were observed. Myocardial and serum levels of monocyte chemoattractant protein-1 were elevated in myocarditis. However, these changes were attenuated by CNP infusion. In addition, treatment with CNP significantly increased myocardial capillary density. Guanylyl cyclase-B, a receptor for CNP, was expressed in myocarditic heart, and cyclic guanosine monophosphate was elevated by CNP infusion. In conclusion, CNP infusion attenuated cardiac function in acute myocarditis through anti-inflammatory and angiogenic effects.
Obata
Hiroaki
H
Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
Yanagawa
Bobby
B
Tanaka
Koichi
K
Ohnishi
Shunsuke
S
Kataoka
Masaharu
M
Miyahara
Yoshinori
Y
Ishibashi-Ueda
Hatsue
H
Kodama
Makoto
M
Aizawa
Yoshifusa
Y
Kangawa
Kenji
K
Nagaya
Noritoshi
N
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology; D018932:Chemokine CCL2 / Q000097:blood; D006152:Cyclic GMP / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay; D006162:Guanylate Cyclase / Q000235:genetics; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D007249:Inflammation / Q000276:immunology / Q000473:pathology / Q000517:prevention & control*; D008297:Male; D009205:Myocarditis / Q000097:blood / Q000000981:diagnostic imaging / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D045283:Natriuretic Agents / Q000008:administration & dosage / Q000494:pharmacology; D020098:Natriuretic Peptide, C-Type / Q000008:administration & dosage / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011863:Radioimmunoassay; D051381:Rats; D011917:Rats, Inbred Lew; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D014463:Ultrasonography; D014841:von Willebrand Factor / Q000378:metabolism
C491768:Ccl2 protein, mouse; D018932:Chemokine CCL2; D045283:Natriuretic Agents; D012333:RNA, Messenger; D014841:von Willebrand Factor; D020098:Natriuretic Peptide, C-Type; D006162:Guanylate Cyclase; D006152:Cyclic GMP