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

Abstract

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% O 2 (normoxic; N), whereas the second were made chronically hypoxic (CH) by breathing 12% O 2 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.