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T. Omae, T. Nagaoka, I. Tanano, A. Yoshida; Pioglitazone Elicits Dilation of Isolated Porcine Arterioles. Invest. Ophthalmol. Vis. Sci. 2010;51(13):5029.
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Pioglitazone, a peroxisome proliferator-activated receptor (PPAR) γ, is used to treat patients with type 2 diabetes. Recent studies have reported that pioglitazone has potent antiinflammatory and atheroprotective effects on vascular tissue and may reduce cardiovascular risk in patients with diabetes. However, it is unclear if pioglitazone is associated with retinal vascular diseases, i.e., diabetic retinopathy. Because we recently reported on the impaired retinal microcirculation in patients with type 2 diabetes, it is necessary to evaluate the effect of pioglitazone on retinal microcirculation. We examined the direct effect and the underlying mechanism of the vasomotor action of pioglitazone in porcine retinal arterioles.
Porcine retinal arterioles (60-90 µm in internal diameter) were isolated, cannulated, and pressurized (55 cmH2O) without flow in this in vitro study. Videomicroscopic techniques were used to record diameter changes in response to pioglitazone.
The retinal arterioles dilated in a dose-dependent manner in response to pioglitazone (10 n-10 µM). This vasodilation decreased by 60% after removal of the endothelium (p<0.0001). The nitric oxide (NO) synthase inhibitor N-nitro-L-arginine methyl ester, L-NAME, (10 µM) inhibited the effect of pioglitazone-induced vasodilation comparable to that produced by denudation (p<0.0001). A nonselective K-channel blocker, tetraethylammonium, and a voltage-gated K (K+) channel inhibitor, 4-AP, inhibited vasodilation (p<0.0001 for both comparisons). Co-administration of L-NAME and 4-AP almost eliminated the vasodilation induced by pioglitazone (p<0.0001).
Pioglitazone elicits both endothelium-dependent and independent dilation of the retinal arterioles. The current findings suggest that endothelium-dependent and independent vasodilation induced by pioglitazone is mediated by the released NO and activation of the K+ channels, respectively.
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