Functional role of α2-adrenoceptor subtypes in the cooling-enhanced vasoconstriction of isolated cutaneous digital veins of the horse

Cooling-enhanced contractile responses in cutaneous arteries have been reported to involve the activation of α2C-adrenoceptors, but their role in cutaneous veins is not clearly understood. The aim was to pharmacologically characterize the subtype of postsynaptic α2-adrenoceptors in the equine digital vein mediating contraction at two temperatures. The increase in isometric tension of endothelium-denuded equine digital vein in response to UK-14304 was studied in the absence and presence of relatively selective α2-adrenoceptor antagonists at temperatures of either 30 °C (the peripheral digit temperature of horses maintained in a thermoneutral environment) or 22 °C. The response to UK-14304 was enhanced by cooling and antagonised by RX-821002 (α2-adrenoceptor non-selective; 30 °C: apparent pKb = 8.5; 22 °C: pKb = 8.2) and yohimbine (α2-adrenoceptor non-selective; 30 °C: apparent pKb = 7.2; 22 °C: apparent pKb = 7.4). The response at 30 °C was non-surmountably antagonised by BRL-44408 (α2A-adrenoceptor-selective; apparent pKb = 8.9) and MK-912 (α2C-adrenoceptor-selective: apparent pKb = 9.9). JP-1302 (α2C-adrenoceptor-selective) surmountably antagonised the response with a low potency (apparent pKb = 5.6) at 30 °C. The response at 22 °C was surmountably antagonised by: BRL-44408 (α2A-adrenoceptor-selective; apparent pKb = 6.5); MK-912 (α2C-adrenoceptor-selective; pKb = 9.7) and JP-1302 (α2C-adrenoceptor-selective; apparent pKb = 7.5). ARC-239 (α2B-adrenoceptor-selective) did not affect the response at either temperature. The apparent potency of the different antagonists and their non-surmountable effect, suggests that the UK-14304 response at 30 °C could be mediated by α2A-adrenoceptors and α2C-adrenoceptors. By contrast, the α2C-adrenoceptor appears to be the main α2-adrenoceptor mediating the augmented response at 22 °C. It is unlikely that the α2B-adrenoceptor subtype contributes at either temperature. These results support the participation of the α2C-adrenoceptors in the cooling-enhanced response to UK-14304 in this cutaneous vein.