Effect of Chronic hypoxia on Carotid vascular responses to noradrenaline in rats

Abstract

Aim: The aim of the present study was to examine whether chronic hypoxia would alter the noradrenaline (NA)-evoked vascular responses in carotid circulation in rats. Furthermore, whether the carotid autoregulatory response to NA-evoked rise in arterial blood pressure (ABP) is compromised by chronic hypoxia or not. Also, the role of tonically synthesised nitric oxide (NO) in these responses was investigated.

Methods: the study was done using two comparable age groups of adult 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 anaesthetised rats, the carotid blood flow (CBF) and carotid vascular conductance (CVC) were recorded during a 3 min infusion of NA at a dose 2.5 μg kg^-1 to induce an acute rise in ABP to 150 mm Hg, the upper limit of autoregulatory range, before and after a bolus dose of the nitric oxide synthase inhibitor, L-NAME (10mg kg^-1).

Results: the NA-evoked rise in ABP was comparable in N and CH rats, but the increase in heart rate was more significant in CH rats. In CH rats, the NA-evoked rise in ABP was associated with a significant reduction in CVC but with no change in CBF, whereas in N rats the reduction in CVC was accompanied with a significant reduction in CBF (p<0.05). In both groups, L-NAME did not accentuate the rise in ABP induced by NA. However, in CH rats the reduction in CBF became more significant after L-NAME.

Conclusion: the carotid vasculature in CH rats is less sensitive to vasopressor effect of NA, when compared to N rats. However, the carotid autoregulatory response to NA-induced rise in ABP was not compromised by chronic hypoxia. Further, it seems that NO does not play a role in the blunted carotid vasoconstrictor responses to NA in CH rats.

Keywords: Chronic hypoxia, carotid circulation, noradrenalin, nitric oxide