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 [NG-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. 65.7 +/- 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 micrograms/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.(ABSTRACT TRUNCATED AT 250 WORDS)
O'Leary
D S
DS
Department of Physiology, Wayne State University School of Medicine, Detroit, Michigan 48201.
Dunlap
R C
RC
Glover
K W
KW
D000818:Animals; D001011:Aorta / Q000502:physiology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D004285:Dogs; D006614:Hindlimb / Q000098:blood supply*; D006940:Hyperemia / Q000139:chemically induced / Q000209:etiology* / Q000503:physiopathology; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000502:physiology*; D010101:Oxygen Consumption / Q000187:drug effects; D012039:Regional Blood Flow / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects
D009569:Nitric Oxide; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester