title: The role of adenosine in the early respiratory and cardiovascular changes evoked by chronic hypoxia in the rat.
abstract: 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.
authors.affiliation: Department of Physiology, The Medical School, Birmingham B15 2TT, UK.
authors.forename: Martin P
authors.initials: MP
authors.lastname: Walsh
authors.forename: Janice M
authors.initials: JM
authors.lastname: Marshall
mesh_terms: 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
chemical_list: 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