The Role of Epoxyeicosatrienoic Acids in Diabetes Mellitus-Induced Impaired Vascular Relaxation of Aortic Rings in Ovariectomized Sprague-Dawley Rats

Abstract EN

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.