Effect of Chronic Hypoxia on Carotid Vascular Responses to Adenosine in Rats

Aim of the work: the present study aims at testing whether chronic hypoxia alters the
dilator vascular responses of rat carotid circulation to adenosine-evoked fall in
arterial blood pressure (ABP). The arterial blood pressure was lowered to the lower
limit of cerebral autoregulatory range giving the chance to further study whether the
carotid autoregulatory response to adenosine-evoked fall in ABP is compromised by
chronic hypoxia or not. A third aim is to investigate whether the role of tonically
synthesized nitric oxide (NO) in dilator responses evoked by adenosine in carotid
vasculature is different in chronic hypoxic rats. Study Design: the study was done
using 2 comparable age groups of adult male Wistar rats; the first were breathing
normal 21% O2 (normoxic; N), whereas the second were made chronically hypoxic
(CH) by breathing 12% O2 for 3 weeks, while they were growing from 7 to 10 weeks.
In anaesthetized rats, the carotid blood flow (CBF) and carotid vascular conductance
(CVC) were recorded during a 3 min infusion of adenosine adjusted at a dose aimed
at lowering ABP to 60 mm Hg, the lower limit of autoregulatory range before and
after a bolus dose of the nitric oxide synthase inhibitor L-NAME (10mg.kg-1).
Results: in chronic hypoxic rats, the adenosine-induced fall in ABP was associated
with a significant increase in CVC but with no significant increase in CBF in contrast
to the significant increase in CBF noticed in N rats. Also, adenosine-evoked increase
in baseline CVC was significantly larger in N than in CH rats. Inhibition of nitric
oxide synthase produced comparable changes on baseline values in CH as in N rats.
In CH rats, L-NAME did not attenuate the increase in CVC evoked by adenosine as it
did in N rats. However, after L-NAME, CBF increased in CH rats. Conclusion: From
these results, it could be suggested that exposing rats to chronic hypoxia for 3 weeks
does not compromise the carotid autoregulatory response to the fall in arterial blood
pressure. However, it seems that adenosine does not exert an active vasodilatation in
carotid circulation of CH rats as it does in N rats. Further, it seems that the
adenosine-evoked increase in CBF in CH rats is largely nitric oxide-independent.