Role of endothelin receptor A and NADPH oxidase in vascular abnormalities.
Vascular dilatation is critically impaired in many diseases and is encountered by an upregulated endothelin receptor A (ETA) in the vasculature in association with a decline in nitric oxide bioavailability. Diabetic vasculopathy is characterized as a compromised vascular dilatation, implicated in many diabetic complications. It appears to be activated ETA and NADPH (nicotinamide adenine dinucleotide phosphate) oxidase in the vasculature. Glucose-lowering agents do not always blunt these changes, as these changes may be progressive leading to the end stage of renal disease. The vascular insults by hypertension, hyperglycemia and aging may share the changes with diabetic vascular beds. Endothelin receptor antagonist CPU0213 and ingredients from plant origins such as CPU86017, p-benzyl-tetra-hydro-berberine are effective in attenuating vascular abnormality by normalizing changes of biomarkers in the vascular wall. The early sign of subclinical atherosclerosis presented as an intima media thickness in the carotid may indicate endothelium dysfunction. The reduced ABI (ankle brachial index) has been taken to predict patients at risk for cardiovascular and cerebrovascular events, and an increased risk of mortality from all causes and cardiovascular disease. An application of agents which suppress the activated ET-NADPH oxidase in the vascular wall is beneficial to attenuate vascular abnormalities. It is worth testing the activity of these agents further for the potential in relieving abnormal vascular activity, reducing the risk of morbidity and mortality in patients at risk.
Dai
De-Zai
DZ
Research Division of Pharmacology, China Pharmaceutical University, Nanjing, China. dezaidai@vip.sina.com
Dai
Yin
Y
D000818:Animals; D055109:Ankle Brachial Index; D001808:Blood Vessels / Q000378:metabolism / Q000503:physiopathology*; D003925:Diabetic Angiopathies / Q000378:metabolism / Q000503:physiopathology; D004730:Endothelium, Vascular / Q000378:metabolism / Q000503:physiopathology; D006801:Humans; D006949:Hyperlipidemias / Q000378:metabolism / Q000503:physiopathology; D006973:Hypertension / Q000503:physiopathology; D019255:NADPH Oxidases / Q000502:physiology*; D009569:Nitric Oxide / Q000378:metabolism / Q000502:physiology; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology; D018384:Oxidative Stress / Q000502:physiology; D058729:Peripheral Arterial Disease / Q000503:physiopathology; D044022:Receptor, Endothelin A / Q000502:physiology*; D015398:Signal Transduction / Q000502:physiology
D044022:Receptor, Endothelin A; D009569:Nitric Oxide; D019255:NADPH Oxidases