Exposure to cigarette smoke abrogates the beneficial effect of ischemic postconditioning.
Cigarette smoking is one of the risk factors for coronary artery disease. Although conditioning decreases infarct size in hearts from healthy animals, comorbidities may render it ineffective. We investigated the effects of cigarette smoke (CS) exposure on intracellular myocardial signaling, infarct size after ischemia-reperfusion, and the potential interference with ischemic conditioning. Exposure of mice to CS increased blood pressure, caused cardiac hypertrophy, and upregulated the nitric oxide synthatse (NOS)/soluble guanylate cyclase (sGC)/cGMP pathway. To test the effect of CS exposure on the endogenous cardioprotective mechanisms, mice were subjected to regional myocardial ischemia and reperfusion with no further intervention or application of preconditioning (PreC) or postconditioning (PostC). Exposure to CS did not increase the infarction compared with the room air (RA)-exposed group. PreC was beneficial for both CS and RA vs. nonconditioned animals. PostC was effective only in RA animals, while the infarct size-limiting effect was not preserved in the CS group. Differences in oxidative stress markers, Akt, and endothelial NOS phosphorylation and cGMP levels were observed between RA and CS groups subjected to PostC. In conclusion, exposure to CS does not per se increase infarct size. The beneficial effect of ischemic PreC is preserved in mice exposed to CS, as it does not affect the cardioprotective signaling; in contrast, PostC fails to protect CS-exposed mice due to impaired activation of the Akt/eNOS/cGMP axis that occurs in parallel to enhanced oxidative stress.
Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.|"George P. Livanos and Marianthi Simou Laboratories," 1st Department of Pulmonary and Critical Care Medicine, Evangelismos Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece; and.
Sofia-Iris
SI
Bibli
Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece.
Ioanna
I
Andreadou
"George P. Livanos and Marianthi Simou Laboratories," 1st Department of Pulmonary and Critical Care Medicine, Evangelismos Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece; and.
Constantinos
C
Glynos
"George P. Livanos and Marianthi Simou Laboratories," 1st Department of Pulmonary and Critical Care Medicine, Evangelismos Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece; and.
Athanasia
A
Chatzianastasiou
"George P. Livanos and Marianthi Simou Laboratories," 1st Department of Pulmonary and Critical Care Medicine, Evangelismos Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece; and.
Dimitris
D
Toumpanakis
"George P. Livanos and Marianthi Simou Laboratories," 1st Department of Pulmonary and Critical Care Medicine, Evangelismos Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece; and.
Spyros
S
Zakynthinos
"George P. Livanos and Marianthi Simou Laboratories," 1st Department of Pulmonary and Critical Care Medicine, Evangelismos Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece; and.
Theodoros
T
Vasilakopoulos
Faculty of Medicine, 2nd Department of Cardiology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece.
Efstathios K
EK
Iliodromitis
Laboratory of Pharmacology, Faculty of Pharmacy, National and Kapodistrian University of Athens, Athens, Greece; apapapet@pharm.uoa.gr.|"George P. Livanos and Marianthi Simou Laboratories," 1st Department of Pulmonary and Critical Care Medicine, Evangelismos Hospital, Faculty of Medicine, National and Kapodistrian University of Athens, Athens, Greece; and.
Andreas
A
Papapetropoulos
D000818:Animals; D001794:Blood Pressure; D015153:Blotting, Western; D006332:Cardiomegaly / Q000378:metabolism / Q000473:pathology; D006152:Cyclic GMP / Q000378:metabolism; D004195:Disease Models, Animal; D006973:Hypertension / Q000378:metabolism / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D057775:Ischemic Postconditioning / Q000379:methods*; D019157:Ischemic Preconditioning, Myocardial / Q000379:methods*; D008297:Male; D051379:Mice; D009203:Myocardial Infarction / Q000378:metabolism* / Q000473:pathology; D015428:Myocardial Reperfusion Injury / Q000378:metabolism* / Q000473:pathology; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism; D018384:Oxidative Stress; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012906:Smoke; D014026:Nicotiana; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D015850:Interleukin-6; D012333:RNA, Messenger; D012906:Smoke; D014409:Tumor Necrosis Factor-alpha; C577686:interleukin-6, mouse; D052250:Nitric Oxide Synthase Type III; C496315:Nos3 protein, mouse; D051057:Proto-Oncogene Proteins c-akt; D006152:Cyclic GMP
cGMP; cigarette smoke; conditioning; eNOS; infarct size