Type 2 diabetes impaired acetylcholine-mediated aortic vasorelaxation in female Zucker Diabetic Fatty rats while enhancing it in males, an effect restored in females by NOX inhibition.
Does type 2 diabetes cause sexually dimorphic impairment of acetylcholine-mediated vasorelaxation in the aorta of ZDF rats?
This study highlights sexual dimorphism in vascular dysfunction in type 2 diabetes, suggesting that superoxide plays a key role in the impaired vasorelaxation observed specifically in females.
Several reports, including our previous studies, indicate that hyperglycemia and diabetes mellitus exert differential effects on vascular function in males and females. This study examines sex differences in the vascular effects of type 2 diabetes (T2D) in an established monogenic model of obesity-induced T2D, Zucker Diabetic Fatty (ZDF) rats. Acetylcholine (ACh) responses were assessed in phenylephrine pre-contracted rings before and after apocynin, a NADPH oxidase (NOX) inhibitor. The mRNA expressions of aortic endothelial NOS (eNOS), and key NOX isoforms were also measured. We demonstrated the following: (1) diabetes had contrasting effects on aortic vasorelaxation in ZDF rats, impairing relaxation to ACh in females while enhancing it in male ZDF rats; (2) inhibition of NOX, a major source of superoxide in vasculature, restored aortic vasorelaxation in female ZDF rats; and (3) eNOS and NOX4 mRNA expressions were elevated in female (but not male) ZDF rat aortas compared to their respective leans. This study highlights sexual dimorphism in ACh-mediated vasorelaxation in the aorta of ZDF rats, suggesting that superoxide may play a role in the impaired vasorelaxation observed in female ZDF rats.
Islam et al. (Mon,) conducted a other in Type 2 diabetes and obesity. Acetylcholine (ACh) and apocynin (NOX inhibitor) vs. Lean rats and male vs female comparison was evaluated on Acetylcholine-mediated aortic vasorelaxation. Type 2 diabetes impaired acetylcholine-mediated aortic vasorelaxation in female Zucker Diabetic Fatty rats while enhancing it in males, an effect restored in females by NOX inhibition.