In this study, we did not compare females to males; however, our data support the notion that MR activation contributes to profound vascular dysfunction in females in conditions of enhanced RAAS activity such as obesity and insulin resistance (Mehta et al., 2016; Davel et al., 2018; Nayyar et al., 2018; Shukri et al., 2018). This evidence concerns the gene NR3C2 and obesity due to melanocortin 4 receptor deficiency.