ET-1 generation is modulated by shear stress that downregulates its release by endothelial cells (10). NO production, stimulated by shear stress, is an important inhibitor of ET-1 release (11), and may thus be a mediator of this effect. Hypoxia, epinephrine, thrombin, Ang II, vasopressin, cytokines, insulin, and growth factors such as TGF-^1 stimulate endothelial release of ET-1. Leptin has also been shown to upregulate ET-1 production by endothelial cells (12), which could explain in part increases of ET-1 in obesity. This may represent a mechanism that relates obesity to frequently associated cardiovascular conditions including hypertension and atherosclerosis, or that contributes to the evolution of the metabolic syndrome toward type 2 diabetes. Peroxisome proliferator-activated receptors (PPARs) are nuclear factors involved in adipocyte differentiation and insulin sensitivity that have been recently shown to exhibit potent anti-inflammatory and antigrowth properties (13-15). Both PPARa and y have been shown in vivo, to inhibit the enhanced expression of preproET-1 mRNA and prevent the progression of hypertension in DOCA-salt rats (16), in which the ET system is activated (17). This effect of fibrates (PPARa activators) and thiazolidinediones (glitazones, PPARy activators) was accompanied by decreased vascular ET-1 expression.
In deoxycorticosterone acetate (DOCA)-salt rats, associated with an increased vascular ET-1 production (17) "enhanced" vascular superoxide generation by reduced nicotinamide adenine dinucleotide phosphate (NADPH) oxidase has been demonstrated, which may contribute to decreased bioavailability of NO, and accordingly, induce endothelial dysfunction (16).
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All you need is a proper diet of fresh fruits and vegetables and get plenty of exercise and you'll be fine. Ever heard those words from your doctor? If that's all heshe recommends then you're missing out an important ingredient for health that he's not telling you. Fact is that you can adhere to the strictest diet, watch everything you eat and get the exercise of amarathon runner and still come down with diabetic complications. Diet, exercise and standard drug treatments simply aren't enough to help keep your diabetes under control.