Interaction between α1- and α2-adrenoreceptors contributes to enhanced constrictor effects of norepinephrine in mesenteric veins compared to arteries

Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation and α-adrenoceptor agonists. We tested the hypothesis that α1- and α2-adrenoceptors interact to enhance adrenergic reactivity of mesenteric veins. We studied neurogenic and agonist-induced constrictions of mesenteric veins and arteries in vitro. Norepinephrine concentration–response curves were left-shifted in veins compared to arteries. UK 14,304 (0.01–1 μM, α2-adrenoceptor receptor agonist) did not constrict arteries or veins but enhanced constrictions and Ca2+ signals mediated by α1-adrenoceptor stimulation in veins. Yohimbine (α2-adrenoceptor receptor antagonist) and MK912 (α2C-adrenoceptor receptor antagonist), but not α2A- or α2B-adrenoceptor antagonists, produced rightward shifts in norepinephrine concentration–response curves in veins. Pharmacological studies revealed that α1D-adrenoceptors mediate venous constrictions. Norepinephrine responses in veins from α2C-adrenoceptor knock-out (KO) mice were not different from wild type veins. Yohimbine inhibited norepinephrine constrictions in α2C-adrenoceptor KO veins suggesting that there is upregulation of other α2-adrenoceptors in α2C-KO mice. These data indicate that α1D- and α2C-adrenoceptors interact in veins but not in arteries. This interaction enhances venous adrenergic reactivity. Mesenteric vein-specific α2-adrenoceptor linked Ca2+ and perhaps other signaling pathways account for enhanced venous adrenergic reactivity.