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.