The Aortic function of Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Possible Involvement of Potassium Channels
UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) rat is a validated model of type 2 diabetes mellitus. UCD-T2DM is characterized by polygenic, adult-onset obesity and spontaneous β-cell failure and, as a result, more closely models the pathophysiology of type 2 diabetes in humans than other rodent models. The objectives of this study were to determine whether the aortic function is altered in male UCD-T2DM rats, and to test the hypothesis that potassium (K+) channels contribute in modulating vascular reactivity of aorta in this model. Endothelium-dependent vasodilation (EDV) to acetylcholine (ACh, 10-8 to 10-5M) was measured in intact aortic rings pre-contracted with phenylephrine (PE, 2μM) before and after pretreatment with tetraethylammonium (TEA, 2 mM), a non-selective K+ channel blocker. Endothelium-independent vasodilation to sodium nitroprusside (SNP, 10-9 to 10-5 M) was assessed in endothelium-denuded rings pre-contracted with PE (2μM). Furthermore, constrictor response curves to PE (10-8 to 10-5 M) were generated before and after incubation with L-NAME (200μM), an endothelial nitric oxide synthase (eNOS) inhibitor. ACh responses were significantly potentiated in aortic rings of male UCD-T2DM rats. Both maximal relaxation and sensitivity to ACh were significantly enhanced compared to those in controls. Incubation of aortic rings with TEA blunted the relaxation responses to ACh in both groups. However, the inhibitory effect of TEA on the ACh-induced relaxation in UCD-T2DM was greater than that in control rats. The smooth muscle sensitivity to NO as measured by SNP-induced relaxation was not altered in aorta of UCD-T2DM group. The responsiveness to PE was significantly enhanced in UCD-T2DM rats. Accordingly, the basal nitric oxide (NO), as indicated by the potentiation of the response to PE after L-NAME, was reduced in aorta of this group. These data, for the first time, show that the aortic function of male UCD-T2DM rats is altered and that K+ channels may be involved. Further studies is required to document the underlying mechanisms of the altered vascular reactivity and to identify the contribution of specific subtypes of K+ channels in the potentiation of aortic endothelial function in this model. Support or Funding Information. Supported by NIHLBI, R15HL128988
Karimi, M. D.,
Graham, J. L.,
Stanhope, K. L.,
Havel, P. J.,
The Aortic function of Male UC Davis Type 2 Diabetes Mellitus (UCD-T2DM) Rats: Possible Involvement of Potassium Channels.
FASEB Journal, 31(Supp 1),