Modulation of adrenergic responses in pressurized resistance arteries by flow

The effects of perfusion on the reactivity of isolated rat resistance mesenteric arteries (200 micron ID) to electrical stimulation and exogenous norepinephrine (NE) were investigated. Diameter constrictions of these arteries that have an intact endothelium in response to the stimuli were significantly greater (P less than 0.05) in the presence than in the absence of flow. Inhibition of NE uptake and metabolism with cocaine, normetanephrine, and pargyline increased constrictor responses to electrical stimulation and NE in the presence and absence of flow, but responses remained larger in the presence of flow. Endothelial cell removal augmented the NE-induced diameter constrictions, which were not different whether or not flow was present. Perfusion at similar flows but a higher shear stress using a dextran solution led to smaller constrictions than obtained at lower shear stress in response to NE. However, NE-induced constrictions at high and low shear stresses were the same after endothelium removal. These observations suggest that NE and elevated levels of shear stress induce the release of relaxing factors from the endothelium, which attenuates direct NE smooth muscle cell constrictor responses.