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Obesity Increases Microvascular Contractility in Response to Sympathetic Nerve Stimulation

Obesity impairs vasodilation and increases contractility in small mesenteric resistance arterioles. The mesenteric microvasculature is innervated by sympathetic and sensory perivascular nerves; however, it isn’t known if changes in innervation contribute to microvascular dysfunction in obesity. The current aim was to characterize the sympathetic and sensory nerve‐mediated responses of isolated mesenteric arterioles from lean and obese mice. We placed 6‐week‐old mice (C57BL/6) on either low or high‐fat diets for 12 weeks. We then isolated third order mesenteric arterioles and used pressure myography to record the effect of perivascular nerve activation by electrical field stimulation (EFS). EFS (20 V, 3 Hz, 2 ms pulse width) caused vasoconstriction which was attenuated by the voltage‐gated Na+ channel blocker tetrodotoxin (TTX, 1 μM). Vasoconstriction (% maximal constriction) was larger in vessels from obese (50% ± 2) mice compared to those from lean (22 ± 5%) animals (P<0.001, n=3, t‐test). To assess the effect of obesity on sensory innervation, vessels were treated with guanethidine 10 μM to suppress sympathetic nerves, and precontracted with 1 μM phenylephrine. Under these conditions, EFS evoked similar relaxations (% maximal relaxation in zero calcium and sodium nitroprusside) in the lean (36% ± 11) and obese (45% ± 16) groups (P>0.5, n=3, t‐test). In conclusion, these data show that during obesity the contractile response to sympathetic innervation is increased without change in the dilatory response to sensory innervation.