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 alpha-adrenergic receptor agonists. In the present study, we tested the hypothesis that alpha(2)-adrenergic receptors (alpha(2)-ARs) contribute to in vitro agonist-induced constriction in veins but not arteries and that alpha(2)-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 alpha(1)-AR antagonist, prazosin (0.003-0.3 microM), produced concentration-dependent rightward shifts of the NE concentration-response curves in arteries but not veins. The alpha(2)-AR agonists, clonidine and UK-14,304, did not constrict arteries or veins in the absence or presence of indomethacin (10 microM) and nitro-L-arginine (NLA; 100 microM). The alpha(2)-AR antagonists, yohimbine (0.003-0.3 microM) and rauwolscine (0.1 microM) did not affect NE responses in SHAM or DOCA-salt arteries but antagonized NE responses in veins. These data indicate that there are different alpha-AR contractile mechanisms in murine mesenteric arteries and veins. Alpha(1)-ARs, but not alpha(2)-ARs, mediate direct contractile responses in arteries and veins while alpha(2)-ARs contribute indirectly to NE-induced constrictions in veins but not arteries in vitro. There may be direct protein-protein interactions between alpha(1)- and alpha(2)-ARs or between their signaling pathways in veins. This contribution of alpha(2)-ARs may account for the greater sensitivity of veins compared to arteries to the contractile effects of NE.