UC Davis type‐2 diabetes mellitus (UCD‐T2DM) model is a novel and validated model of type‐2 diabetes exhibiting etiology very similar to clinical T2DM seen in humans. This model is characterized by polygenic adult‐onset obesity and diabetes observed in both sexes along with development of insulin resistance, impaired glucose tolerance, and subsequent β‐cell decompensation. We have previously shown that vascular reactivity in mesenteric arteries (MA) of male UCD‐T2DM is altered. Endothelium‐dependent hyperpolarizing factors (EDHF) is an important regulator of vascular tone, especially in small vessels such as MA. The objective of this study was to investigate the contribution of small or intermediate conductance calcium‐activated potassium channels (SKca & IKca) in modulating vascular function of MA in this model. Endothelium‐dependent vasodilation (EDV) to acetylcholine (ACh, 10−8 to 10−5 M) in pre‐contracted MA with phenylephrine (PE, 2μM) was measured before and after pretreatment with indomethacin (Indo, 10μm), a cyclooxygenase inhibitor, followed by addition of L‐NAME (200uM), a nitric oxide synthase inhibitor, and then Apamin (1μm), a selective inhibitor of SKca; and TRAM‐34 (1μm), a selective inhibitor of IKca. We demonstrated that the sensitivity to ACh‐induced relaxation was significantly reduced in MA from male UCD‐T2DM rats compared to controls. Addition of L‐NAME reduced Indo‐insensitive vasorelaxation in both control and diabetic animals. However, when compared with that of control, the effect of L‐NAME was much greater in MA of UCD‐T2DM, indicating a reduced contribution of EDHFtype relaxation or an enhanced role of NO in this disease model. The remaining EDV to ACh which is referred to as the L‐NAME/Indo‐insensitive component, or EDHF‐type relaxation was subsequently blocked by inhibiting intermediate (but not small) conductance calcium‐activated potassium channels in MA of diabetic model. In control animals, however, incubation of MA with apamin (a SKca inhibitor) led to a further reduction of EDV. The subsequent addition of TRAM‐34 eventually blunted the EDHF‐type relaxation in this group. These data, for the first time, show that the contribution of EDHF in EDV is reduced in the MA of UCD‐T2DM group, and the down regulation of SKca may be involved. Clearly, further studies will be needed to document the underlying mechanism(s) of altered vascular function in male UCD‐T2DM rats.Support or Funding InformationSupported by NIH/NHLBIThis abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Background Due to the popularity of excessive alcohol consumption, there is an increasing need for hangover symptom remedies. Most commercially available hangover treatment products have not been tested for efficacy through clinical study. Aims The purpose of this pilot study was to characterize the activity of a commercially available hangover product, The Hangover Secret (THS). Methods This was a randomized, double‐blinded, placebo‐controlled, crossover pilot study. Healthy volunteers of 21‐ to 40‐years‐old were eligible for participation, and received either THS or placebo on two different occasions. Participants were given 43 mL of whiskey every twenty minutes for up to 3 hours to achieve a blood alcohol concentration (BrAC) ≥ 0.12%. Hangover severity was assessed using the Acute Hangover Scale (AHS) and Acute Hangover Severity Scale (AHSS) validated tools. Results Nine participants completed the study. AHS scores increased from baseline to 7 am by 4.11 ± 3.17 and 1.26 ± 2.29 for the placebo and active arms respectively ( P = .16). AHS headache scores increased from baseline to 7 am by 2.44 ± 1.67 and 1.11 ± 1.17 for the placebo and active arms respectively ( P = .06). AHSS scores increased from baseline to 7 am by 1.0 ± 1.05 and 0.41 ± 1.08, for the placebo and active arms respectively ( P = .30). There was no significant difference between average BrAC at 7 am between the placebo and active arms. Conclusion THS showed positive signals in the prevention of alcohol‐induced hangover, especially headaches. The improvements with THS surpassed the minimum clinically important difference in overall AHS score and three individual AHS symptoms scores (hangover, headache, and thirsty). THS's reduction in AHS or AHSS scores did not reach statistical significance likely due to the small sample size. Larger studies with appropriate sample sizes are needed in light of these promising findings.