Alpha2‐Adrenoreceptors contribute to norepinephrine‐induced constriction of mesenteric veins

Abstract

Mesenteric veins are more sensitive to stimulation by norepinephrine (NE) than arteries. Furthermore, veins desensitize more slowly than arteries in response to continuous stimulation by NE. These differences might be related to expression of functional α2 adrenergic receptors (α 2ARs) in venous smooth muscle cells. These studies investigated the contribution of α 2ARs to NE induced constriction of murine mesenteric veins in vitro. Phenylephrine (PE) and NE caused concentration dependent (1 – 1000 nM) constrictions of mesenteric veins. The α2AR agonist, UK14304 (10-1000 nM) did not cause venous constriction. However, yohimbine (300 nM), an α 2AR blocker produced a 5-fold rightward shift of the NE dose-response curve in veins, but not arteries (EC50 = 0.015 vs 0.08μM for NE and NE + yohimbine, respectively). BRL44408 (100 nM α 2AAR antagonist) or imiloxan (1 μM, α 2B antagonist) did change significantly NE dose-response curves in veins. In contrast, MK912 (10nM, α 2CAR antagonist) produced a 4-fold rightward shift (EC50s:0.01 vs 0.04 for NE and NE + MK912, respectively). This shift was comparable to the effect produced by yohimbine (300 nM). These data indicate that α2AR agonists do not directly constrict mesenteric veins; however, they contribute to constriction caused by the αAR non-selective agonist NE. These data also indicate that the main α 2AR subtype mediating the actions of NE in murine mesenteric veins is the α 2CAR.