1. CNP infusion attenuates cardiac dysfunction and inflammation in myocarditis.
- Author
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Obata H, Yanagawa B, Tanaka K, Ohnishi S, Kataoka M, Miyahara Y, Ishibashi-Ueda H, Kodama M, Aizawa Y, Kangawa K, and Nagaya N
- Subjects
- Animals, Blood Pressure drug effects, Blood Vessels drug effects, Blood Vessels pathology, Chemokine CCL2 blood, Cyclic GMP metabolism, Enzyme-Linked Immunosorbent Assay, Guanylate Cyclase genetics, Heart physiopathology, Heart Rate drug effects, Inflammation immunology, Inflammation pathology, Male, Myocarditis blood, Myocarditis diagnostic imaging, Myocardium metabolism, Myocardium pathology, Natriuretic Agents administration & dosage, Natriuretic Agents pharmacology, Natriuretic Peptide, C-Type administration & dosage, RNA, Messenger genetics, RNA, Messenger metabolism, Radioimmunoassay, Rats, Rats, Inbred Lew, Reverse Transcriptase Polymerase Chain Reaction, Swine, Ultrasonography, von Willebrand Factor metabolism, Heart drug effects, Inflammation prevention & control, Myocarditis prevention & control, Natriuretic Peptide, C-Type pharmacology
- 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.
- Published
- 2007
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