Hyperglycemia can promote the release of various vasoactive mediators, namely, insulin-like growth factor-1 (IGF-1), VEGF, and nitric oxide (NO) from the kidney, resulting in the dilation of renal arterioles; however, due to the local elevation of angiotensin II (Ang II) and endothelin-1 (ET-1), the efferent arterioles contract, leading to the formation of glomerular hypertension and the occurrence of DN (61). Here, EDN1 is linked to Hyperglycemia.