ROLE OF ENDOTHELIUM-DERIVED RELAXING FACTOR IN HINDLIMB REACTIVE AND ACTIVE HYPEREMIA IN CONSCIOUS DOGS

We tested in conscious dogs whether endothelium-derived relaxing factor (EDRF) mediates hindlimb reactive and active hyperemia. Hindlimb reactive hyperemia was observed in response to release of a 1-min occlusion of the terminal aorta, and in separate studies, hindlimb active hyperemic responses to graded dynamic (treadmill) exercise were observed before and after inhibition of EDRF production [N-G-nitro-L-arginine methyl ester (L-NAME); 5 mg/kg iv)]. At rest, L-NAME significantly increased mean arterial pressure (MAP) from control levels (100.6 +/- 6.2 vs. 125.0 +/- 7.3 mmHg) and significantly decreased heart rate (HR) (94.1 +/- 4.6 vs. 65.1 +/- 3.8 beats/min), terminal aortic blood flow (TAQ) (0.51 +/- 0.01 vs. 0.33 +/- 0.03 l/min), and terminal aortic vascular conductance (TAC) (5.2 +/- 0.4 vs. 2.7 +/- 0.1 ml. min(-1).mmHg(-1)). L-NAME also significantly reduced the hindlimb hyperemia induced by intra-arterial acetylcholine (5 mu g/kg). During reactive hyperemia L-NAME significantly reduced both the duration and maximal increase in TAC (16.2 +/- 1.6 vs. 10.4 +/- 0.8 s and 24.5 +/- 3.3 vs. 21.0 +/- 3.1 ml.min(-1) mmHg(-1), respectively). During graded exercise, MAP was significantly higher and HR significantly lower at each work load after L-NAME. During mild exercise, TAQ was significantly lower after L-NAME, whereas at higher work loads, L-NAME had no significant effect on TAQ. TAC was significantly reduced at each work load after L-NAME, but the difference from control remained constant with increasing work load; L-NAME caused a constant offset in TAC during graded exercise. We conclude that EDRF may play a physiological role in hindlimb reactive hyperemia but does not appear to be important in mediating hindlimb active hyperemia during graded dynamic exercise.