PR-39, a proline/arginine-rich antimicrobial peptide, exerts cardioprotective effects in myocardial ischemia-reperfusion.
OBJECTIVE
PR-39, a proline/arginine-rich antimicrobial peptide, has been shown to inhibit the NADPH oxidase activity of polymorphonuclear leukocytes (PMNs) by blocking assembly of this enzyme. We hypothesized that PR-39 could attenuate PMN-induced cardiac dysfunction by suppression of superoxide production.


METHODS
We examined the effects of PR-39 in isolated ischemic (20 min) and reperfused (45 min) rat hearts administered PMNs at the onset of reperfusion.


RESULTS
PR-39 (4 or 10 microg/ml) given i.v. 30 min prior to ischemia-reperfusion (I-R) significantly improved left ventricular developed pressure (LVDP, P<0.01) and the maximal rate of development of LVDP (i.e. +dP/dt max, P<0.01) compared to I-R hearts obtained from rats given 0.9% NaCl. PR-39-treated PMNs (10 microg/ml) also significantly attenuated cardiac contractile dysfunction after I-R (P<0.01). Superoxide release was significantly reduced (P<0.01) in N-formylmethionyl-leucylphenylalanine stimulated PMNs pretreated with 4 or 10 microg/ml PR-39. PR-39 also significantly attenuated P-selectin expression on the rat coronary microvascular endothelium and CD18 upregulation in rat PMNs. In addition, PR-39 significantly reduced PMN vascular adherence and infiltration into the post-ischemic myocardium.


CONCLUSIONS
These results provide evidence that PR-39 significantly attenuates PMN-induced cardiac contractile dysfunction in the I-R rat heart at least in part via suppression of superoxide release. This cardioprotection occurred both by inhibition of PMN and endothelial NADPH oxidase.
Ikeda
Y
Y
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, 1020 Locust Street, Philadelphia, PA 19107-6799, USA.
Young
L H
LH
Scalia
R
R
Ross
C R
CR
Lefer
A M
AM
D000818:Animals; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D023181:Antimicrobial Cationic Peptides / Q000627:therapeutic use*; D018821:CD18 Antigens / Q000378:metabolism; D004730:Endothelium, Vascular / Q000378:metabolism / Q000473:pathology; D008297:Male; D009200:Myocardial Contraction / Q000187:drug effects; D015428:Myocardial Reperfusion Injury / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000502:physiology / Q000637:transplantation; D009924:Organ Culture Techniques; D019007:P-Selectin / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013481:Superoxides / Q000378:metabolism
D000900:Anti-Bacterial Agents; D023181:Antimicrobial Cationic Peptides; D018821:CD18 Antigens; D019007:P-Selectin; D013481:Superoxides; C072212:PR 39