Measurement of nitric oxide release evoked by systemic hypoxia and adenosine from rat skeletal muscle in vivo.
It is accepted that NO plays a role in hypoxic vasodilatation in several tissues. For rat hindlimb muscle there is evidence that during systemic hypoxia endogenously released adenosine acts on endothelial A1 receptors to evoke dilatation in a NO-dependent fashion, implying requirement for, or mediation by, NO. We tested in vivo whether systemic hypoxia and adenosine release NO from muscle. In anaesthetized rats, arterial blood pressure (ABP) and femoral blood flow (FBF) were recorded allowing computation of femoral vascular conductance (FVC). Blood samples taken from femoral artery and vein allowed electrochemical measurement of plasma [NO] after reduction of NO3- and NO2-. Systemic hypoxia and adenosine infusion for 5 min each, evoked an increase in FVC that was attenuated by the NO synthase (NOS) inhibitor l-NAME (Group 1, n = 8) and adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX, Group 2, n = 6). Concomitant systemic hypoxia and adenosine infusion evoked increases in venous-arterial [NO] difference ([NO](v-a)) from -1.4 +/- 0.85 to 6.6 +/- 1.6 and 2.3 +/- 0.78 to 8.4 +/- 1.8 nmol l(-1), respectively (mean +/- s.e.m), which were abolished by l-NAME (-0.72 +/- 0.90 to -0.87 +/- 0.74 and 0.72 +/- 0.85 to -0.97 +/- 1.1 nmol l(-1), respectively). DPCPX also abolished the hypoxia-evoked increase in [NO](v-a) (control -4.2 +/- 1.8 to 12.5 +/- 3.7 nmol l(-1), with DPCPX -0.63 +/- 2.6 to 3.3 +/- 2.9 nmol l(-1)) and decreased the adenosine-evoked increase in [NO](v-a) (control 1.1 +/- 1.5 to 24 +/- 14, with DPCPX -0.43 +/- 2.9 to 12 +/- 5.9 nmol l(-1)). These results allow the novel conclusion that the muscle vasodilatation of systemic hypoxia is partly mediated by adenosine acting at endothelial A1 receptors to stimulate synthesis and release of NO, which then induces dilatation.
Ray
Clare J
CJ
Department of Physiology, The Medical School, University of Birmingham, Birmingham B15 2TT, UK. c.j.ray@bham.ac.uk
Marshall
Janice M
JM
D000241:Adenosine / Q000378:metabolism*; D000818:Animals; D000860:Hypoxia / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000378:metabolism*; D009569:Nitric Oxide / Q000097:blood*; D019001:Nitric Oxide Synthase / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000378:metabolism*
D043682:Receptor, Adenosine A1; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000241:Adenosine