Differential contributions of alpha-1 and alpha-2 adrenoceptors to vasoconstriction in mesenteric arteries and veins of normal and hypertensive mice

Mesenteric veins are more sensitive than arteries to the constrictor effects of sympathetic nerve stimulation and α-adrenergic receptor agonists. In the present study, we tested the hypothesis that α2-adrenergic receptors (α2-ARs) contribute to in vitro agonist-induced constriction in veins but not arteries and that α2-AR function is down-regulated in mesenteric arteries and veins in deoxycorticosterone acetate–salt (DOCA–salt) hypertension. Norepinephrine (NE) concentration–response curves were similar in SHAM and DOCA–salt arteries and veins indicating that adrenergic reactivity of mesenteric blood vessels is not altered in murine DOCA–salt hypertension in vitro. Veins were 30-fold more sensitive to NE than arteries. The α1-AR antagonist, prazosin (0.003–0.3 μM), produced concentration-dependent rightward shifts of the NE concentration–response curves in arteries but not veins. The α2-AR agonists, clonidine and UK-14,304, did not constrict arteries or veins in the absence or presence of indomethacin (10 μM) and nitro-l-arginine (NLA; 100 μM). The α2-AR antagonists, yohimbine (0.003–0.3 μM) and rauwolscine (0.1 μM) did not affect NE responses in SHAM or DOCA–salt arteries but antagonized NE responses in veins. These data indicate that there are different α-AR contractile mechanisms in murine mesenteric arteries and veins. α1-ARs, but not α2-ARs, mediate direct contractile responses in arteries and veins while α2-ARs contribute indirectly to NE-induced constrictions in veins but not arteries in vitro. There may be direct protein–protein interactions between α1- and α2-ARs or between their signaling pathways in veins. This contribution of α2-ARs may account for the greater sensitivity of veins compared to arteries to the contractile effects of NE.