Contribution of α(2)-adrenoceptors and Y(1) neuropeptide Y receptors to the blunting of sympathetic vasoconstriction induced by systemic hypoxia in the rat

There is evidence that sympathetically evoked vasoconstriction in skeletal muscle is blunted in systemic hypoxia, but the mechanisms underlying this phenomenon are not clear. In Saffan-anaesthetized Wistar rats, we have studied the role of α(2)-adrenoceptors and neuropeptide Y (NPY) Y(1) receptors in mediating vasoconstriction evoked by direct stimulation of the lumbar sympathetic chain by different patterns of impulses in normoxia (N) and systemic hypoxia (H: breathing 8% O(2)). Patterns comprised 120 impulses delivered in bursts over a 1 min period at 40 or 20 Hz, or continuously at 2 Hz. Hypoxia attenuated the evoked increases in femoral vascular resistance (FVR) by all patterns, the response to 2 Hz being most affected (40 Hz bursts: N = 3.25 ± 0.75 arbitrary resistance units (RU); H = 1.14 ± 0.29 RU). Yohimbine (Yoh, α(2)-adrenoceptor antagonist) or BIBP 3226 (Y(1)-receptor antagonist) did not affect baseline FVR. In normoxia, Yoh attenuated the responses evoked by high frequency bursts and 2 Hz, whereas BIBP 3226 only attenuated the response to 40 Hz (40 Hz bursts: N + Yoh = 2.1 ± 0.59 RU; N + BIBP 3226 = 1.9 ± 0.4 RU). In hypoxia, Yoh did not further attenuate the evoked responses, but BIBP 3226 further attenuated the response to 40 Hz bursts. These results indicate that neither α(2)-adrenoceptors nor Y(1) receptors contribute to basal vascular tone in skeletal muscle, but both contribute to constrictor responses evoked by high frequency bursts of sympathetic activity. We propose that in systemic hypoxia, the α(2)-mediated component represents about 50% of the sympathetically evoked constriction that is blunted, whereas the contribution made by Y(1) receptors is resistant. Thus we suggest the importance of NPY in the regulation of FVR and blood pressure increases during challenges such as systemic hypoxia.