Carperitide induces coronary vasodilation and limits infarct size in canine ischemic hearts: role of NO.
Carperitide is effective for heart failure (HF) owing to its diuretic and vasodilatory effects. This recombinant peptide may also have direct cardioprotective effects because carperitide reduces the severity of heart failure and limits infarct size. Because coronary vasodilation is an important cardioprotective treatment modality, we investigated whether carperitide increased coronary blood flow (CBF) and improved myocardial metabolic and contractile dysfunction during ischemia in canine hearts. We also tested whether carperitide is directly responsible for limiting the infarct size. We infused carperitide at 0.025-0.2 μg kg(-1) min(-1) into the canine coronary artery. A minimum dose of 0.1 μg kg(-1) min(-1) was required to obtain maximal vasodilation. To test the effects of carperitide on ischemic hearts, we reduced perfusion pressure in the left anterior descending coronary artery such that CBF decreased to one-third of the baseline value. At 10 min after carperitide was infused at a dose of 0.1 μg kg(-1) min(-1), we observed increases in CBF, fractional shortening (FS) and pH levels in coronary venous blood without concomitant increases in cardiac nitric oxide (NO) levels; these changes were attenuated using either the atrial natriuretic peptide receptor antagonist HS-142-1 or the NO synthase inhibitor L(ω)-nitroarginine methyl ester (L-NAME). Cyclic guanosine monophosphate (GMP) levels in the coronary artery were elevated in response to carperitide that also limited the infarct size after 90 min of ischemia and subsequent reperfusion. Again, these effects were blunted by L-NAME. Carperitide increases CBF, reduces myocardial contractile and metabolic dysfunction and limits infarct size. In addition, NO is necessary for carperitide-induced vasodilation and cardioprotection in ischemic hearts.
1] Department of Cardiovascular Science and Technology, Kyoto Prefectural University School of Medicine, Kyoto, Japan [2] Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
Hiroshi
H
Asanuma
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Shoji
S
Sanada
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
Masanori
M
Asakura
1] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan [2] Department of Medical Biochemistry, Osaka University Graduate School of Medicine, Suita, Japan.
Yoshihiro
Y
Asano
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
Jiyoong
J
Kim
Department of Physiology, Tokai University Graduate School of Medicine, Isehara, Japan.
Yoshiro
Y
Shinozaki
Department of Physiology, Tokai University Graduate School of Medicine, Isehara, Japan.
Hidezo
H
Mori
Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Tetsuo
T
Minamino
1] Department of Cardiovascular Medicine, Osaka University Graduate School of Medicine, Suita, Japan [2] Department of Medical Biochemistry, Osaka University Graduate School of Medicine, Suita, Japan.
Seiji
S
Takashima
Department of Cardiovascular Medicine, National Cerebral and Cardiovascular Center, Suita, Japan.
Masafumi
M
Kitakaze
D000818:Animals; D009320:Atrial Natriuretic Factor / Q000627:therapeutic use*; D003326:Coronary Circulation / Q000187:drug effects; D003331:Coronary Vessels / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D004285:Dogs; D005260:Female; D009200:Myocardial Contraction / Q000187:drug effects; D009203:Myocardial Infarction / Q000188:drug therapy* / Q000473:pathology; D017202:Myocardial Ischemia / Q000188:drug therapy* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000473:pathology; D009206:Myocardium / Q000378:metabolism; D009569:Nitric Oxide / Q000378:metabolism*; D017461:Receptors, Atrial Natriuretic Factor / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects*; D014665:Vasodilator Agents / Q000627:therapeutic use*
C472955:NPPA protein, human; D014665:Vasodilator Agents; D009569:Nitric Oxide; D009320:Atrial Natriuretic Factor; D000242:Cyclic AMP; D017461:Receptors, Atrial Natriuretic Factor