(Circulation. 1999;99:2951-2957.)
© 1999 American Heart Association, Inc.
Basic Science Reports |
Exercise Improves Flow-Mediated Vasodilatation of Skeletal Muscle Arteries in Rats With Chronic Heart Failure
Role of Nitric Oxide, Prostanoids, and Oxidant Stress
From the Department of Pharmacology, VACOMED, Rouen University Medical School, Rouen, France.
Correspondence to C. Thuillez, MD, PhD, Service de Pharmacologie, CHU de Rouen, 76031 Rouen Cedex, France. E-mail Christian.Thuillez{at}chu-rouen.fr
Background—Flow-mediated dilatation (FMD) of the peripheral arteries may be impaired in chronic heart failure (CHF), and this could contribute to the increased peripheral resistance and exercise intolerance that occur with this disease. Physical exercise improves the FMD of large conduit arteries in CHF, but whether a similar impairment also occurs in smaller arteries is unknown. The mechanisms of the changes in FMD after CHF or exercise are also unknown.
Methods and Results—FMD was assessed in isolated, perfused, and
preconstricted gracilis muscle arteries from sham-operated rats or CHF
rats (coronary artery ligation) who were either sedentary or
exercised (30-minute swimming period twice a day for 10 weeks, starting
7 days after ligation). In animals with hemodynamic and
echographic signs of CHF, FMD was abolished and converted into
vasoconstriction (percent change in diameter after 370 µL/min flow:
sham, 42±5%; CHF, -4±3%; P<0.05). Exercise
partially restored FMD (18±3%; P<0.05 versus CHF). In
sham rats, FMD was abolished by the nitric oxide–synthase
inhibitor
N
-nitro-L-arginine (L-NA) but
unaffected by the cyclooxygenase
inhibitor diclofenac or the free radical scavenger
N-(2-mercaptopropionyl)-glycine (MPG). In arteries from sedentary CHF
rats, FMD was not modified by L-NA, but it was partially restored by
diclofenac or MPG. In exercised CHF rats, FMD was abolished by L-NA and
only moderately improved by diclofenac or MPG. Likewise,
endothelial nitric oxide synthase mRNA expression
(determined by reverse transcription polymerase chain reaction at the
level of the gracilis muscle) was reduced by CHF, and this was
prevented by exercise.
Conclusions—CHF abolishes the FMD of small arteries by impairing the nitric oxide pathway, increasing oxidant stress, and releasing a prostanoid-contracting factor. Exercise partially restores FMD by increasing expression of endothelial nitric oxide synthase and preventing the production of vasoconstrictor prostanoids and free radicals. Such restoration of FMD might contribute to the increase in exercise capacity after physical exercise in CHF.
Key Words: exercise • dilatation • heart failure • muscle, skeletal • prostaglandins • nitric oxide synthase
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