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

Abstract

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 α 2 -adrenergic receptors (α 2 -ARs) contribute to in vitro agonist-induced constriction in veins but not arteries and that α 2 -AR function is down-regulated in mesenteric arteries and veins in deoxycorticosterone acetate-salt (DOCA-salt) hypertension. Norepinephrine (NE) concentrationresponse 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 α 1 -AR antagonist, prazosin (. 003-0.3μM), produced concentration-dependent rightward shifts of the NE concentrationresponse curves in arteries but not veins. The α 2 -AR agonists, clonidine and UK-14,304, did not constrict arteries or veins in the absence or presence of indomethacin (10 μM) and nitro-Larginine (NLA; 100 μM). The α 2 -AR antagonists, yohimbine (.003-0.3 μM) and rauwolscine (0.1μM) 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. α 1 -ARs, but not α 2 -ARs, mediate direct contractile responses in arteries and veins while α 2 -ARs contribute indirectly to NE-induced constrictions in veins but not arteries in vitro. There may be direct protein-protein interactions between α 1 -and α 2 -ARs or between their signaling pathways in veins. This contribution of α 2 -ARs may account for the greater sensitivity of veins compared to arteries to the contractile effects of NE.

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

“…Therefore, we studied postjunctional mechanisms that could contribute to the enhanced adrenergic reactivity of mesenteric veins in vitro . Previous work suggested that α 2 -adrenoceptors contribute to norepinephrine-induced constrictions of murine mesenteric veins but not arteries (Perez-Rivera et al, 2007). This was confirmed in the present study where we showed that yohimbine inhibits norepinephrine-mediated constriction of veins but not arteries.…”

“…This might be due to artery-vein differences in α-adrenoceptor expression. α 2 -Adrenoceptors potentiate constrictions mediated by α 1 -adrenoceptors in mesenteric veins but not arteries (Perez-Rivera et al, 2007) confirming that α 2 -adrenoceptors play a more prominent role constriction of veins than arteries (Flavahan et al, 1984, Ruffolo, 1986, Patel et al, 1981). A direct coupling between α 1 - and α 2 -adrenoceptors may mediate the functional interaction as occurs in the cauda epididymis (Haynes and Hill, 1996) and glial cells (Wilson and Minneman 1991).…”

Neurogenic Vascular Responses in Male Mouse Mesenteric Vascular Beds

“…It is widely accepted that norepinephrine is the neurotransmitter for sympathetic adrenergic nerves and activates α 1 -and α 2 -adrenoceptors. In the male mouse mesenteric artery, but not vein, norepinephrine has been shown to cause vasoconstriction via activation through mainly postsynaptic α 1 -adrenoceptors (22). Therefore, it is likely that the PNS-induced vasoconstrictor response is mainly mediated by postsynaptic α 1 -adrenoceptors, which are activated by norepinephrine released from adrenergic nerves.…”

Adenosinergic System in the Mesenteric Vessels

“…Once released, noradrenaline can act on a variety of receptors on the vascular smooth muscle cells. Previous in vitro studies have found contractile responses to be mediated by activation of the α 1 adrenoceptor in mesenteric arteries and both α 1 and α 2 adrenoceptors in the mesenteric vein (Perez-Rivera et al, 2007). These adrenoceptors are G-protein linked receptors that are coupled to an intracellular increase of inositol 1,4,5-triphosphate (IP3).…”