Dendroaspis natriuretic peptide protects the post-ischemic myocardial injury.
The present study used isolated rat hearts to investigate whether (1) Dendroaspis natriuretic peptide (DNP) is protective against post-ischemic myocardial dysfunction, and (2) whether the cardioprotective effects of DNP is related to alteration of Bcl-2 family protein levels. The excised hearts of Sprague-Dawley rats were perfused on a Langendorff apparatus with Krebs-Henseleit solution with a gas mixture of 95% O2 and 5% CO2. Left ventricular end-diastolic pressure (LVEDP, mmHg), left ventricular developed pressure (LVDP, mmHg) and coronary flow (CF, ml/min) were continuously monitored. In the presence of 50 nM DNP, all hearts were perfused for a total of 100 min consisting of a 20 min pre-ischemic period followed by a 30 min global ischemia and 50 min reperfusion. Lactate dehydrogenase (LDH) activity in the effluent was measured during reperfusion. Treatment with DNP alone improved the pre-ischemic LVEDP and post-ischemic LVEDP significantly comparing with the untreated control hearts during reperfusion. However, DNP did not affect the LVDP, heart rate (HR, beats/min), and CF. Bcl-2, an anti-apoptotic protein expressed in ischemic myocardium of DNP+ischemia/reperfusion (I/R) group, was higher than that in I/R alone group. Bax, a pro-apoptotic protein expressed in ischemic myocardium of DNP+I/R group, has no significant difference compared with I/R alone group. These results suggest that the protective effects of DNP against I/R injury would be mediated, at least in part, through the increased ratio of Bcl-2 to Bax protein after ischemia-reperfusion.
Ha
Ki-Chan
KC
Department of Pharmacology and Institute of Cardiovascular Research, Chonbuk National University Medical School, Jeonju 561-182, Republic of Korea.
Piao
Cheng-Shi
CS
Chae
Han-Jung
HJ
Kim
Hyung-Ryong
HR
Chae
Soo-Wan
SW
D000818:Animals; D017209:Apoptosis; D004546:Elapid Venoms / Q000378:metabolism / Q000494:pharmacology*; D019254:Genes, bcl-2; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008856:Microscopy, Fluorescence; D017202:Myocardial Ischemia / Q000188:drug therapy / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy / Q000378:metabolism / Q000517:prevention & control*; D045283:Natriuretic Agents / Q000378:metabolism / Q000494:pharmacology / Q000627:therapeutic use; D010455:Peptides / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051028:bcl-2-Associated X Protein / Q000187:drug effects / Q000378:metabolism
C075597:Dendroaspis natriuretic peptide; D004546:Elapid Venoms; D036341:Intercellular Signaling Peptides and Proteins; D045283:Natriuretic Agents; D010455:Peptides; D051028:bcl-2-Associated X Protein; D007770:L-Lactate Dehydrogenase