Differential contribution of pannexin‐1 channels to agonist and neurogenic constriction of mesenteric arteries and veins from normotensive and DOCA‐salt hypertensive rats

Abstract

Norepinephrine (NE) and ATP are constrictor transmitters released from perivascular sympathetic nerves. ATP efflux through smooth muscle pannexin‐1 channels contributes to á1 adrenergic receptor (α1‐AR) mediated arterial constriction. We tested the hypotheses that pannexin‐1 contributes to: 1) α1‐AR mediated constriction of mesenteric veins (MV); 2) neurogenic constriction of mesenteric arteries (MA) and MV; 3) pannexin‐1 mechanisms are impaired in DOCA‐salt hypertension in rats. We used MA and MV in vitro. Drugs were added to organ bath solutions. Constrictions were measured using video microscopy. Perivascular nerves were activated by focal electrical stimulation. Western blot was used to measure pannexin‐1 protein. Phenylephrine (PE) concentration‐response curves (CRCs) were similar in MA and MV from sham and DOCA‐salt rats. PE‐CRCs were right‐shifted to a similar extent by mefloquine (1 μM, pannexin‐1 blocker) in MA but not MV from sham and DOCA‐salt rats. Mefloquine did not alter neurogenic constrictions in MA or MV. Pannexin‐1 protein was expressed in MA and MV. These data indicate that pannexin‐1 mechanisms contribute to agonist but not neurogenic constriction of MA in normotensive and hypertensive rats. This mechanism does not contribute to adrenergic constriction of MV. Nerve released and exogenous NE may access different constrictor mechanisms in MA. (Supported by P01HL070687)