Effects of nitric oxide synthase inhibition on the muscle blood flow response to exercise in rats with heart failure.
OBJECTIVE
The aim of this study was to investigate whether the role of nitric oxide (NO) in regulating blood flow (BF) to working skeletal muscle is impaired in chronic heart failure (CHF).


METHODS
The effect of NG-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO synthesis, was studied in conscious rats with and without CHF due to myocardial infarction (MI). BF to the hindquarter musculature was measured with radiolabelled microspheres during exercise after 4 min of treadmill running (10% grade, 20 m/min) before and after L-NAME (20 mg/kg i.a.) administration.


RESULTS
Before L-NAME administration, BF measured in the total hindquarter musculature was less (P < 0.05) during exercise in rats with a large MI (MI size; 44 +/- 2% of the left ventricular endocardial circumference; n = 8) when compared with sham-operated rats (SHAM; n = 10) and rats with a small MI (MI size; 25 +/- 4%; n = 5). The BF measured during exercise following L-NAME administration was similar between the 3 groups. Of the 28 individual hindquarter muscles, BF was reduced in 23 and 19 muscles following the administration of L-NAME for the SHAM rats and rats with a small MI, respectively. In comparison, BF was reduced to only 4 of 28 muscles in rats with a large MI.


CONCLUSIONS
These results suggest that the contribution of the NO pathway to the hyperaemic BF responses found in the hindquarter muscles during exercise could be attenuated in rats with CHF. This attenuation of the NO pathway may be associated with the impairment of skeletal muscle BF distribution during exercise in CHF.
Hirai
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T
Department of Anatomy, Kansas State University, Manhattan 66506, USA.
Zelis
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R
Musch
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TI
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006333:Heart Failure / Q000503:physiopathology*; D006339:Heart Rate / Q000187:drug effects; D018482:Muscle, Skeletal / Q000098:blood supply*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D010805:Physical Conditioning, Animal; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester