Carperitide, a synthetic
alpha-human atrial natriuretic peptide (
ANP) is a newly developed
drug for the treatment of
heart failure. However, effects of
carperitide on susceptibility to
ischemia reperfusion injury are left to be determined. Isolated rat hearts were subjected to Langendorff perfusion. Six hearts received 0.1 microM of
carperitide for 10 min, 6 hearts received 1 mM of a NO
synthetase inhibitor
N(G)-nitro-L-arginine methyl ester (
L-NAME) for 5 min before the infusion of
carperitide, 6 hearts received 0.02 microM of a PKC
synthetase inhibitor
chelerythrine chloride for 5 min before the infusion of
carperitide, 6 hearts received 100 microM of a selective mitochondrial
ATP-sensitive
potassium (
KATP) channel blocker 5-dehydroxydecanoate (5HD) before the infusion of
carperitide, 6 hearts received 10 microM of a
soluble guanylate cyclase inhibitor
methylene blue for 5 min before the infusion of
carperitide, and 6 hearts served as a control with no
drug infusion. All hearts were then subjected to 20 min of global
ischemia followed by 120 min of reperfusion. Left ventricular pressures and coronary flow were measured throughout the experiment and
infarct size was detected at the end of experiment. Both plasma and tissue cGMP levels were also determined. The results showed: (1)
Carperitide significantly reduced
infarct size compared to control (26.1 +/- 2.8 vs. 42.7 +/- 2.3%,
carperitide vs. control, p < 0.05). This effect was reversed by
L-NAME,
chelerythrine and 5HD, but not
methylene blue. (2) Plasma cGMP levels were increased in
carperitide-treated group. This effect was reversed by
L-NAME (0.16 +/- 0.03 vs. 1.04 +/- 0.09* vs. 0.28 +/- 0.02 nmol/L, control vs.
carperitide vs.
L-NAME, *p < 0.01 vs. control). We conclude that preischemic infusion of
carperitide exerts cardioprotective effects possibly through NO-PKC dependent pathway followed by mitochondrial
KATP channel activation.