1. Carbon monoxide levels experienced by heavy smokers impair aerobic capacity and cardiac contractility and induce pathological hypertrophy.
- Author
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Bye A, Sørhaug S, Ceci M, Høydal MA, Stølen T, Heinrich G, Tjønna AE, Najjar SM, Nilsen OG, Catalucci D, Grimaldi S, Contu R, Steinshamn S, Condorelli G, Smith GL, Ellingsen O, Waldum H, and Wisløff U
- Subjects
- Animals, Blood Pressure drug effects, Calcium physiology, Cardiomegaly pathology, Cardiomegaly physiopathology, Cyclic GMP metabolism, Female, Heart physiopathology, Myocardial Contraction drug effects, Myocytes, Cardiac physiology, Oxygen metabolism, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, RNA-Binding Proteins, Rats, Rats, Wistar, Sarcoplasmic Reticulum Calcium-Transporting ATPases metabolism, Transcription Factors metabolism, Carbon Monoxide toxicity, Cardiomegaly chemically induced, Heart drug effects, Myocytes, Cardiac drug effects, Smoking adverse effects
- Abstract
Cigarette smoke contains hundreds of potentially toxic compounds and is an important risk factor for cardiovascular disease. However, the key components responsible for endothelial and myocardial dysfunction have not been fully identified. The objective of the present study was to determine the cardiovascular effects of long-term inhalation of carbon monoxide (CO) administrated to give concentrations in the blood similar to those observed in heavy smokers. Female rats were exposed to either CO or air (control group) (n = 12). The CO group was exposed to 200 ppm CO (100 h/wk) for 18 mo. Rats exposed to CO had 24% lower maximal oxygen uptake, longer (145 vs. 123 microm) and wider (47 vs. 25 microm) cardiomyocytes, reduced cardiomyocyte fractional shortening (12 vs. 7%), and 26% longer time to 50% re-lengthening than controls. In addition, cardiomyocytes from CO-exposed rats had 48% lower intracellular calcium (Ca2 +) amplitude, 22% longer time to Ca2 + decay, 34% lower capacity of sarcoplasmic reticulum Ca2 +-ATPase (SERCA2a), and 37% less t-tubule area compared to controls. Phosphorylation levels of phospholamban at Ser16 and Thr17 were significantly reduced in the CO group, whereas total concentration of phospholamban and SERCA2a were unchanged. Cardiac atrial natriuretic peptide, vascular endothelial growth factor, cyclic guanosine monophosphate, calcineurin, calmodulin, pERK, and pS6 increased, whereas pAkt and pCaMKII delta remained unchanged by CO. Endothelial function and systemic blood pressure were not affected by CO exposure. Long-term CO exposure reduces aerobe capacity and contractile function and leads to pathological hypertrophy. Impaired Ca2 + handling and increased growth factor signaling seem to be responsible for these pathological changes.
- Published
- 2008
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