DIFFERENTIAL IMPACT OF MYOGENIC ACTIVATION ON DILATOR RESPONSES IN CEREBRAL AND SKELETAL MUSCLE RESISTANCE ARTERIOLES OF OBESE ZUCKER RATS

The metabolic syndrome causes alterations to not only individual indices of vascular dilator/constrictor reactivity, but also in their integration for the overall regulation of vascular tone. Using the obese Zucker rat (OZR), we interrogated relationships between intraluminal pressure (myogenic activation; ILP) and indices of dilator reactivity in gracilis muscle arterioles (GA) and middle cerebral arteries (MCA) to determine if differences exist between these two beds. In isolated GA, dilator responses to hypoxia and acetylcholine were blunted in OZR vs. LZR and demonstrated a strong inverse relationship between ILP and dilator reactivity. Normalization of vascular oxidant stress with TEMPOL and/or blockade of PGH 2 /TxA 2 receptors with SQ‐29548 removed ~60% of the inhibitory effect of ILP on dilator reactivity to these stimuli in GA. In contrast, isolated MCA, while exhibiting similar impairments to low PO 2 and Ach, had a less robust ILP‐dependent impairment on dilator reactivity (~35%). Treatment of MCA with TEMPOL, SQ‐29548 or both abolished the effects of increased ILP. In both GA and MCA, dilator responses to adenosine were unaffected by changes to ILP. These results suggest that altered myogenic activation can strongly impact resistance arteriolar dilation (GA>MCA) and that oxidant stress‐based elevations in TxA 2 production may be a major contributor to this impairment. (NIH DK64668, RR2865AR)