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 o f nitric oxide (NO) in regulating blood flow (BF) to working skeletal muscle is impaired in chronic heart failure (CHF). Methods: The effect of N-G-nitro-L-arginine methyl ester (L-NAME), an inhibitor of NO syn thesis, was studied in conscious rats with and without CHF due to myoc ardial infarction (MI). BF to the hindquarter musculature was measured with radiolabelled microspheres during exercise after 4 min of treadm ill 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 exerc ise in rats with a large MI (MI size; 44 +/- 2% of the left ventricula r endocardial circumference; n = 8) when compared with sham-operated r ats (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 muscle s, 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 c omparison, BF was reduced to only 4 of 28 muscles in rats with a large MI. Conclusions: These results suggest that the contribution of the N O pathway to the hyperaemic BF responses found in the hindquarter musc les during exercise could be attenuated in rats with CHF. This attenua tion of the NO pathway may be associated with the impairment of skelet al muscle BF distribution during exercise in CHF.