Abstract
OBJECTIVE: To use the OZR model of the metabolic syndrome to determine the impact of dilator stimuli on MA of GA and MCA. We tested the hypothesis that increased oxidant stress and TxA2 exacerbate MA, and prevent its blunting with dilator stimuli, in OZR. METHODS: GA/MCA from OZR and LZR was pressurized ex vivo. MA was determined under control conditions and following challenge with acetylcholine, hypoxia, and adenosine. Responses were also evaluated after pre-treatment with TEMPOL (antioxidant) and SQ-29548 (PGH2 /TxA2 receptor antagonist). RESULTS: MA was increased (and dilator responses decreased) in GA/MCA from OZR, dependent on the endothelium and ROS. In GA, the impact of ROS on MA and dilator effects was largely via TxA2 , while in MCA, this appeared was more dependent on NO bioavailability. Intrinsic responses of GA/MCA to carbacyclin, U46619, and NO donors were similar between strains. CONCLUSIONS: A developing ROS-based endothelial dysfunction in MCA and GA of OZR contributes to an enhanced MA of these vessels. Although treatment of GA/MCA with TEMPOL attenuates MA in OZR, the mechanistic contributors to altered MA, distal to ROS, differ between the two resistance vessels.