The role of adenosine in the early respiratory and cardiovascular changes evoked by chronic hypoxia in the rat.
Experiments were performed on anaesthetized normoxic (N) rats and chronically hypoxic rats that had been exposed to 12% O2 for 1, 3 or 7 days (1, 3 or 7CH rats). The adenosine A1 receptor antagonist DPCPX did not affect the resting hyperventilation of 1-7CH rats breathing 12% O2 and increased resting heart rate (HR) in 1CH rats only. DPCPX partially restored the decreased baseline arterial pressure (ABP) and increased femoral vascular conductance (FVC) of 1 and 3CH rats, but had no effect in N or 7CH rats. DPCPX also attenuated the decrease in arterial blood pressure (ABP) and increase in FVC evoked by acute hypoxia in N and 1-7CH rats. The non-selective adenosine receptor antagonist 8-SPT had no further effect on baselines or cardiovascular responses to acute hypoxia, but attenuated the hypoxia-evoked increase in respiratory frequency in 1-7CH rats. In N, and 1 and 3CH rats, the inducible nitric oxide synthase (iNOS) inhibitor aminoguanidine had no effect on baselines or increases in FVC evoked by acetylcholine. We propose: (i) that tonically released adenosine acting on A1 receptors reduces HR in 1CH rats and stimulates endothelial NOS in 1 and 3CH rats to decrease ABP and increase FVC, the remaining NO-dependent tonic vasodilatation being independent of iNOS activity; (ii) that in 7CH rats, tonic adenosine release has waned; (iii) that in 1-7CH rats, adenosine released by acute hypoxia stimulates A1 but not A2 receptors to produce muscle vasodilatation, and stimulates carotid body A2 receptors to increase respiration.
Walsh
Martin P
MP
Department of Physiology, The Medical School, Birmingham B15 2TT, UK.
Marshall
Janice M
JM
D000241:Adenosine / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure; D002319:Cardiovascular System / Q000187:drug effects*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006146:Guanidines / Q000494:pharmacology; D006339:Heart Rate; D006439:Hemodynamics; D000860:Hypoxia; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D043682:Receptor, Adenosine A1 / Q000187:drug effects*; D012119:Respiration / Q000187:drug effects*; D012129:Respiratory Function Tests; D013806:Theophylline / Q000031:analogs & derivatives / Q000494:pharmacology; D014970:Xanthines / Q000494:pharmacology
D004791:Enzyme Inhibitors; D006146:Guanidines; D043682:Receptor, Adenosine A1; D014970:Xanthines; C031433:8-(4-sulfophenyl)theophylline; C051360:1,3-dipropyl-8-cyclopentylxanthine; D013806:Theophylline; D019001:Nitric Oxide Synthase; D000241:Adenosine; C004479:pimagedine; D019331:NG-Nitroarginine Methyl Ester