Endothelin-1 and diabetic complications: focus on the vasculature

Diabetes is not only an endocrine but also a vascular disease. Cardiovascular complications are the leading cause of morbidity and mortality associated with diabetes. Diabetes affects both large and small vessels and hence diabetic complications are broadly classified as microvascular (retinopathy, nephropathy and neuropathy) and macrovascular (heart disease, stroke and peripheral arterial disease) complications. Endothelial dysfunction, defined as an imbalance of endothelium-derived vasoconstrictor and vasodilator substances, is a common denominator in the pathogenesis and progression of both macro and microvascular complications. While the pathophysiology of diabetic complications is complex, endothelin-1 (ET-1), a potent vasoconstrictor with proliferative, profibrotic, and proinflammatory properties, may contribute to many facets of diabetic vascular disease. This review will focus on the effects of ET-1 on function and structure of microvessels (retina, skin and mesenteric arteries) and macrovessels (coronary and cerebral arteries) and also discuss the relative role(s) of endothelin A (ET(A)) and ET(B) receptors in mediating ET-1 actions.