The role of adenosine in the early respiratory and cardiovascular changes evoked by chronic hypoxia in the rat

Martin Walsh, Janice Marshall

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11 Citations (Scopus)


Experiments were performed on anaesthetized normoxic (N) rats and chronically hypoxic rats that had been exposed to 12% O-2 for 1, 3 or 7 days (1, 3 or 7CH rats). The adenosine A(1) receptor antagonist DPCPX did not affect the resting hyperventilation of 1-7CH rats breathing 12% O-2 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 A(1) 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 A(1) but not A(2) receptors to produce muscle vasodilatation, and stimulates carotid body A(2) receptors to increase respiration.
Original languageEnglish
Pages (from-to)277-289
Number of pages13
JournalThe Journal of Physiology
Publication statusPublished - 1 Jun 2006


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