Impaired Mesenteric Arterial Function of Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Possible Involvement of Small Conductance Calcium-activated Potassium Channels (SKca)
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 ?-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 and TRAM-34 (1?m), 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 Information Supported by NIH/NHLBI This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.
Graham, J. L.,
Stanhope, K. L.,
Havel, P. J.,
Impaired Mesenteric Arterial Function of Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Possible Involvement of Small Conductance Calcium-activated Potassium Channels (SKca).
FASEB Journal, 32(Supp 1),