Downregulation of the alpha‐1 adrenergic receptor, which mediates direct contractile responses in mesenteric arteries26, 58, 59 together with the elevation of Klf4, which inhibits the expression of contractile marker genes in vascular smooth muscle cells60 in male HSD mice are indicative of reduced vascular reactivity and responsiveness to adrenergic stimulation, whereas enhanced contractile response observed in females may contribute to the development of hypertension by increasing peripheral resistance.61 This evidence concerns the gene KLF4 and hypertensive disorder.