Myogenic Reactivity in Mesenteric Arteries of High Fat Fed Rats

Obesity may lead to abnormal vascular reactivity associated with increased production of reactive oxygen species (ROS) and reduced bioavailability of nitric oxide (NO). Therefore, we hypothesized that feeding rats a high fat diet (HFD; 60%) for 6 weeks would result in obesity and elevated ROS thereby enhancing vasoconstrictor tone. Consistent with this hypothesis, HFD‐fed rats gained significantly more weight, associated with larger fat pads, over the 6 week diet compared to chow‐fed controls. Likewise, lipid peroxidation was greater in the HFD‐fed rats indicative of enhanced oxidative stress. To assess vascular tone, the inner diameter of isolated small mesenteric resistance arterioles (80–120 μm inner diameter) from Sprague‐Dawley rats was quantified during increasing transluminal pressure steps (20 to 120 mmHg). Contrary to our hypothesis, percent myogenic tone (% active tone) was significantly blunted (6.0 ± 0.6% at 120 mmHg) in the overweight rats compared to chow‐fed controls (22.2 ± 9.0% at 120 mmHg). Interestingly, this diminished constrictor reactivity was likely due to increased NO production since NO synthase inhibition with LNNA (100 μM) restored percent myogenic tone (19.1 ± 6.8% at 120 mmHg). In contrast to our hypothesis, the addition of the superoxide dismutase and catalase mimetic, EUK134 (10 μM), had no effect on myogenic reactivity in arteries from HFD‐fed rats suggesting that elevated ROS do not play a major role in the blunted myogenic response in this setting.