Abstract
Aim The present study was aimed at determining if type 1 diabetes mellitus (DM) affects vascular function and at elucidating the mechanisms mediating vasorelaxation in both nonovariectomized and ovariectomized Sprague-Dawley (SD) rats. Materials and Methods Eighty female SD rats were divided into four groups: nonovariectomized healthy (non-OVX-CTR) and diabetic (non-OVX-DM) rats and ovariectomized healthy (OVX-CTR) and diabetic (OVX-DM) rats. Bilateral ovariectomy was performed at the age of 5 weeks, and type 1 DM was induced by streptozotocin at the age of 6 weeks. At the age of 12 weeks, acetylcholine-induced relaxation (AChIR) was assessed in aortic rings in the absence/presence of L-NAME, Indomethacin, and MS-PPOH. Aortic tissue mRNA expression of eNOS, iNOS, COX-1, COX-2, thromboxane synthase 1 (TBXAS1), CYP4A1, CYP4A3, and CYP2J3, as well as plasma oxidative stress, was measured. Results AChIR did not differ in non-OVX-DM rats compared to non-OVX-CTR ones. AChIR was significantly reduced in the OVX-DM group compared to the OVX-CTR group. MS-PPOH did not reduce AChIR in OVX-DM rats as it did in OVX-CTR ones. CYP4a3 mRNA expression in OVX-DM rats was significantly lower compared to that in the OVX-CTR group. Conclusions Female sex hormones may protect vasorelaxation in type 1 diabetic rats. Type 1 diabetes impairs vasorelaxation in response to ACh in ovariectomized rats (but not in nonovariectomized rats) by affecting vasorelaxation pathways mediated by EETs.
Highlights
The most important complications of diabetes mellitus (DM) relate to vascular disease, which affects both microvasculature and macrovasculature [1], while endothelial dysfunction is implicated in the pathogenesis of such diabetic vascular disorders [2, 3]
The blood glucose level was significantly increased in both the non-OVX-DM and OVX-DM groups compared to their corresponding controls, which confirmed the successful development of the diabetes model in our experimental protocol
thiobarbituric acid-reactive substances (TBARS) was significantly increased in non-OVX-DM rats compared to non-OVX-CTR ones, while in OVX-DM rats, TBARS was not significantly different from that in OVX-CTR ones (Table 1)
Summary
The most important complications of diabetes mellitus (DM) relate to vascular disease, which affects both microvasculature (neuropathy, diabetic nephropathy, and retinopathy) and macrovasculature (peripheral arterial disease, coronary artery disease) [1], while endothelial dysfunction is implicated in the pathogenesis of such diabetic vascular disorders [2, 3]. It has been shown that DM impairs vascular reactivity by increasing response to physiological vasoconstrictors and decreasing reactivity to vasodilators [4, 5]. Disturbed endothelium-dependent vasodilation in diabetic rats may occur due to compromised bioavailability of the normally protective vasodilator mediators, such as nitric oxide (NO). International Journal of Endocrinology vasodilators, such as epoxyeicosatrienoic acids (EETs) [8] Their biological roles in vascular function are extremely important—they serve as an endothelium-derived hyperpolarizing factor and have proangiogenic, anti-inflammatory, antiapoptotic, and profibrinolytic effects [9]. Either EET-dependent vasodilation becomes an important compensatory mechanism in vessels with a lower bioavailability of NO (as they are in DM), or, in contrast, impaired vasodilation occurs due to decreased activity of EETs in animals with DM [10]. We have previously demonstrated that EETs have an important role in mediating restored relaxation responses of aortic rings in diabetic rats subjected to hyperbaric oxygen treatment [11, 12]
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