Our appreciation of the vascular endothelium has changed considerably over the last decade. This organ, finally recognized as such, participates actively in vasomotor regulation and haemostasis. It secretes several relaxing and contracting factors which act locally to determine resting vascular tone. One of the relaxing factors, EDRF/NO plays an important physiological role as it contributes to the rapid adaptation of blood flow to various pharmacological and mechanical stimuli, thereby ensuring maintenance of adequate tissue perfusion. Nitric oxide (NO) is an ubiquitous factor which was crowned "molecule of the year 1992" by the scientific review Science. Its effects extend well beyond those on the cardiovascular system. Endothelial dysfunction is observed in many pathological states such as atherosclerosis, reperfusion injury, postangioplasty endothelial regeneration, degeneration of venous bypass grafts, pure spastic angina, hypertension and diabetes. It is associated with decreased production of EDRF/NO, which probably contributes significantly to the aggravation of endothelial and parietal lesions and to the natural progression of atherosclerotic disease in general. This article describes the principal vasoactive factors secreted by the endothelium and goes on to list the physiologic cardiovascular effects of EDRF/NO in detail, and to review the different pathologies associated with a disorder of secretion of this factor.
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The goal of this study was to determine the cellular mechanisms of vascular endothelial dysfunction in rats irradiated with gamma-rays. Acetylcholine (Ach)-induced relaxation of rat thoracic aorta rings was measured as a test of endothelial integrity and function. The data obtained allow suggest that endothelial function is impaired in aorta from g-irradiated rats mainly due to the loss of EDRF/NO-dependent, but not EDHF-dependent relaxation.
View Article and Find Full Text PDFAm J Physiol Regul Integr Comp Physiol
February 2009
Georgetown University Hypertension, Kidney and Vascular Disorders Center, Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007 USA.
We reported impaired endothelium-derived relaxation factor/nitric oxide (EDRF/NO) responses and constitutive nitric oxide synthase (cNOS) activity in subcutaneous vessels dissected from patients with essential hypertension (n = 9) compared with normal controls (n = 10). We now test the hypothesis that the patients in this study have increased circulating levels of the cNOS inhibitor, asymmetric dimethylarginine (ADMA), or the lipid peroxidation product of linoleic acid, 13-hydroxyoctadecadienoic acid (HODE), which is a marker of reactive oxygen species. Patients had significantly (P < 0.
View Article and Find Full Text PDFCirc Res
September 2007
Division of Nephrology and Hypertension, Georgetown University, Washington, DC 20007, USA.
Asymmetric dimethylarginine (ADMA), which inhibits NO synthase, is inactivated by N(G),N(G)-dimethylarginine dimethylaminohydrolase (DDAH). We tested whether DDAH-1 or -2 regulates serum ADMA (S(ADMA)) and/or endothelium-derived relaxing factor (EDRF)/NO. Small inhibitory (si)RNAs targeting DDAH-1 or -2, or an siRNA control were given intravenously to rats.
View Article and Find Full Text PDFPlatelets
July 2007
2nd Department of Medicine, University Medical School, Debrecen, Hungary.
Limited information seems to be available about the role of reduced endothelial production of endotheliumderived relaxing factor (EDRF)-nitrate/nitrite (NO) in the pathogenesis of diabetic angiopathy in insulindependent diabetes. A report of urinary and serum nitrate/nitrite, glucometabolic parameters, endothelial and in vivo platelet activation markers of 22 insulin dependent diabetics (IDDM) patients are given. Urinary and serum nitrate/nitrite concentrations were reduced in IDDM.
View Article and Find Full Text PDFClin Exp Pharmacol Physiol
August 2002
Department of Pharmacology, Faculty of Medicine, Gazi University, Ankara, Turkey.
1. In the present study, endothelium-derived relaxing factor (EDRF/nitric oxide (NO)), conversion of big endothelin (ET)-1 to endothelin-1 (ET-1) and the role of reactive oxygen species were investigated in kidneys isolated from glycerol (GLY)-pretreated rabbits. 2.
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