title: CNP infusion attenuates cardiac dysfunction and inflammation in myocarditis.
abstract: 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.
authors.affiliation: Department of Regenerative Medicine and Tissue Engineering, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita, Osaka 565-8565, Japan.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Obata
authors.forename: Bobby
authors.initials: B
authors.lastname: Yanagawa
authors.forename: Koichi
authors.initials: K
authors.lastname: Tanaka
authors.forename: Shunsuke
authors.initials: S
authors.lastname: Ohnishi
authors.forename: Masaharu
authors.initials: M
authors.lastname: Kataoka
authors.forename: Yoshinori
authors.initials: Y
authors.lastname: Miyahara
authors.forename: Hatsue
authors.initials: H
authors.lastname: Ishibashi-Ueda
authors.forename: Makoto
authors.initials: M
authors.lastname: Kodama
authors.forename: Yoshifusa
authors.initials: Y
authors.lastname: Aizawa
authors.forename: Kenji
authors.initials: K
authors.lastname: Kangawa
authors.forename: Noritoshi
authors.initials: N
authors.lastname: Nagaya
mesh_terms: 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
chemical_list: 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