Brain natriuretic peptide reverses the effects of myocardial stunning in rabbit myocardium.
We tested the hypothesis that brain natriuretic peptide (BNP) would decrease the effects of myocardial stunning in rabbit hearts. We also examined the mechanisms responsible for these effects. In two groups of anesthetized open-chest rabbits, myocardial stunning was produced by 2 15-min occlusions of the left anterior descending artery separated by 15 min of reperfusion. The treatment group had BNP (10(-3) mol/l) topically applied to the stunned area. Hemodynamic and functional parameters were measured. Coronary flow and O2 extraction were used to determine myocardial O2 consumption. In separate animals, we measured the function of isolated control and simulated ischemia (95% N2/5% CO2, 15 min)-reperfusion ventricular myocytes with BNP or C-type natriuretic peptide (10(-8)-10(-7) mol/l) followed by KT5823 (10(-6) mol/l, cyclic GMP protein kinase inhibitor). In the in vivo control group, baseline delay to contraction was 47+/-4 ms and after stunning it increased to 71+/-10 ms. In the treatment group, baseline delay to contraction was 40+/-7 ms, and after stunning and BNP it did not significantly increase (43+/-6 ms). Neither stunning nor BNP administration affected regional O2 consumption. In control myocytes, BNP (10(-7) mol/l) decreased the percent shortening from 6.7+/-0.4 to 4.5+/-0.2%; after KT5823 administration, the percent shortening increased to 5.4+/-0.5%. In ischemia-reperfusion myocytes, BNP (10(-7) mol/l) decreased the percent shortening less from 5.0+/-0.5 to 3.8+/-0.2%; KT5823 administration did not increase the percent shortening (3.8+/-0.2%). BNP similarly and significantly increased cyclic GMP levels in control and stunned myocytes. The data illustrated that BNP administration reversed the effects of stunning and its mechanism may be independent of the cyclic GMP protein kinase.
Anyadike
Chukwuma
C
Heart and Brain Circulation Laboratory, Department of Surgery, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, NJ 08854-5635, USA.
Scholz
Peter M
PM
Zhang
Qihang
Q
Katz
Elizabeth
E
Weiss
Harvey R
HR
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002227:Carbazoles / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D006152:Cyclic GMP / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology*; D009200:Myocardial Contraction / Q000187:drug effects*; D017682:Myocardial Stunning / Q000188:drug therapy*; D020097:Natriuretic Peptide, Brain / Q000502:physiology / Q000627:therapeutic use*; D010101:Oxygen Consumption / Q000187:drug effects; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011817:Rabbits
D002227:Carbazoles; D007211:Indoles; D047428:Protein Kinase Inhibitors; D020097:Natriuretic Peptide, Brain; C073601:KT 5823; D006152:Cyclic GMP