Abstract
Adenosine is a potent vasodilator of retinal blood vessels and is implicated to be a major regulator of retinal blood flow during metabolic stress, but little is known about the impact of diabetes on the role of adenosine in regulation of retinal hemodynamics. Therefore, we examined how diabetes affects adenosine-induced vasodilation of retinal arterioles. Male Wistar rats were treated with streptozotocin (80 mg/kg, intraperitoneally), and experiments were performed 6–8 weeks later. Rats were treated with tetrodotoxin (50 μg/kg, intravenously [i.v.]) to eliminate any nerve activity and prevent movement of the eye and infused with methoxamine continuously to maintain adequate systemic circulation. Fundus images were captured with a digital camera that was equipped with a special objective lens, and diameters of retinal arterioles were measured. Adenosine increased diameters of retinal arterioles and decreased systemic blood pressure. These responses were significantly attenuated by the nitric oxide synthase inhibitor NG-nitro-l-arginine methyl ester (30 mg/kg, i.v.) and the adenosine triphosphate-dependent K+ (KATP) channel blocker glibenclamide (20 mg/kg, i.v.). The depressor responses to adenosine were reduced in diabetic rats, whereas diabetes did not alter vasodilation of retinal arterioles to adenosine. In contrast, both depressor response and vasodilation of retinal arteriole to acetylcholine were reduced in diabetic rats. The retinal vasodilator responses to adenosine and acetylcholine observed in diabetic rats were diminished by NG-nitro-l-arginine methyl ester. There were no differences in the responses to pinacidil, a KATP channel opener, between the diabetic and nondiabetic rats. These results suggest that both the activation of nitric oxide synthase and opening of KATP channels contribute to the vasodilator effects of adenosine in rats in vivo. However, diabetes has no significant impact on the vasodilation mediated by these mechanisms in the retinal circulation.
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This study was supported in part by Grant-in Aid for Scientific Research from the Ministry of Education, Culture, Sports, Science and Technology, Japan and by the Uehara Memorial Foundation.
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Nakazawa, T., Mori, A., Saito, M. et al. Vasodilator effects of adenosine on retinal arterioles in streptozotocin-induced diabetic rats. Naunyn-Schmied Arch Pharmacol 376, 423–430 (2008). https://doi.org/10.1007/s00210-007-0233-z
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DOI: https://doi.org/10.1007/s00210-007-0233-z