atrial-natriuretic-factor and Diabetic-Retinopathy

Topics: Animals; Atrial Natriuretic Factor; Catecholamines; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Angiopathies; Diabetic Nephropathies; Diabetic Retinopathy; Humans; Hypertension; Insulin Resistance; Renin-Angiotensin System; Sodium

Ginseng (Araliaceae) has multiple pharmacological actions because of its diverse phytochemical constituents. The aims of the present study are to evaluate the preventive effects of North American ginseng on diabetic retinopathy and cardiomyopathy and to delineate the underlying mechanisms of such effects. Models of both type 1 (C57BL/6 mice with streptozotocin-induced diabetes) and type 2 diabetes (db/db mice) and age-matched and sex-matched controls were examined. Alcoholic ginseng root (200 mg/kg body weight, daily oral gavage) extract was administered to groups of both type 1 and type 2 diabetic mice for 2 or 4 months. Dysmetabolic state in the diabetic mice was significantly improved by ginseng treatment. In both the heart and retina of diabetic animals, ginseng treatment significantly prevented oxidative stress and diabetes-induced upregulations of extracellular matrix proteins and vasoactive factors. Ginseng treatment in the diabetic animals resulted in enhancement of stroke volume, ejection fraction, cardiac output, and left ventricle pressure during systole and diastole and diminution of stroke work. In addition, mRNA expressions of atrial natriuretic factor and brain natriuretic factor (molecular markers for cardiac hypertrophy) were significantly diminished in ginseng-treated diabetic mice. These data indicate that North American ginseng prevents the diabetes-induced retinal and cardiac biochemical and functional changes probably through inhibition of oxidative stress.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 2; Diabetic Cardiomyopathies; Diabetic Retinopathy; Extracellular Matrix Proteins; Heart; Male; Mice; Mice, Inbred C57BL; Natriuretic Peptide, Brain; Oxidative Stress; Panax; Phytotherapy; Plant Extracts; Plant Roots; Retina

Atrial natriuretic peptide (ANP) is a known vascular antipermeability and antiangiogenic factor, but its possible alteration during the early stages of diabetic retinopathy has not yet been explored. The present study sought to investigate the expression of ANP and its receptors using a model of streptozotocin (STZ) induced diabetes in the rat.. Diabetes was induced in male Wistar rats by an intraperitoneal injection of STZ. Age matched animals served as control. One and 3 months after the onset of diabetes, the expression of ANP mRNA and that of its receptors (NPRA, NPRB, NPRC) and the immunoreactive ANP was quantified in retinal tissue by quantitative real time reverse transcription-polymerase chain reaction (RT-PCR) and radioimmunoassay, respectively. The locations of ANP and glial fibrillary acidic protein (GFAP) in normal and diabetic retinas were also established by immunohistochemistry.. No alteration in the gene expression of the retinal natriuretic peptide system was noted after 1 month of diabetes. However, 3 months after the onset of diabetes, significantly diminished ANP and NPRC mRNA levels were detected in the retina of diabetic rats compared to controls, while NPRA, NPRB mRNA levels remained unchanged. At this time point, retinal ANP concentrations were significantly diminished in the diabetic rats compared to control rats. However, at 1 month retinal ANP concentrations in diabetic retina were similar to control rats. Diabetes caused the downregulation of ANP protein expression in the layers of the retina at 3 months after the induction of diabetes. ANP immunoreactivity was detected in the cell bodies of the astrocytes and in their processes enveloping vessels.. The downregulation of ANP and NPRC in retinas of diabetic rats suggests a role for this peptide in experimental diabetic retinopathy. Further studies should address the possible involvement of the ANP/NPRC system in the pathophysiology of diabetic retinopathy.

Topics: Animals; Atrial Natriuretic Factor; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetic Retinopathy; Down-Regulation; Gene Expression Regulation; Glial Fibrillary Acidic Protein; Guanylate Cyclase; Immunoenzyme Techniques; Male; Rats; Rats, Wistar; Receptors, Atrial Natriuretic Factor; Retina; Reverse Transcriptase Polymerase Chain Reaction; RNA, Messenger

Atrial natriuretic peptide (ANP) has been recently described as an endogenous inhibitor of the synthesis and angiogenic action of vascular endothelial growth factor (VEGF). Given VEGF's key role in promoting neovascularization in proliferative diabetic retinopathy (PDR), this study was designed to evaluate the possibility that ANP could be involved in the neovascular and fibrotic complications of PDR.. We determined ANP by radioimmunoassay in plasma and vitreous humor samples collected from diabetic patients with and without PDR and from non-diabetic subjects. ANP was also immunohistochemically localized in the epiretinal membranes of patients with PDR.. Vitreous ANP concentrations were significantly higher in patients with active PDR compared to patients with quiescent PDR, diabetes without PDR or controls <0.05. Significant differences were also observed between vitreous ANP levels in diabetic patients without PDR and control subjects. There was no significant correlation between serum and vitreous ANP levels in any of the patient groups. ANP was detected in the fibrovascular epiretinal tissue of patients with PDR.. Diabetic patients with active neovascularization have significantly higher levels of ANP in the vitreous humor than those without active PDR. Diabetic patients without PDR were also found to have significantly higher vitreous ANP levels than non-diabetic patients. Since plasma and vitreous ANP concentrations were found to be unrelated, we suggest intraocular ANP synthesis and/or an increase in the release of ANP into the vitreous, as opposed to diffusion from the blood, as the main factors contributing to the high vitreous ANP levels observed in diabetic patients. In the fibrovascular epiretinal tissue of these patients, ANP was found to be localized in vascular, glial, fibroblast-like and retinal pigment epithelium cells. Our findings suggest a role for ANP in PDR.

Topics: Adult; Aged; Atrial Natriuretic Factor; Diabetes Mellitus, Type 1; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Epiretinal Membrane; Female; Glial Fibrillary Acidic Protein; Humans; Immunoenzyme Techniques; Keratins; Male; Middle Aged; Radioimmunoassay; Retinal Neovascularization; Vitrectomy; Vitreous Body

Thickening of the basement membrane and other structural alterations of the vascular walls occur frequently in patients with diabetes. The vascular response to atrial natriuretic peptide (ANP) is also altered in these patients. Abnormal vascular response in diabetes may be due to alteration of vascular physicochemical properties induced by accumulation of components of vascular basement membrane. The aim of this study was to evaluate the relationship between circulating levels of the 7 S domain of type IV collagen (7 S-collagen), and ANP in normotensive type 2 diabetic patients with or without retinopathy. Forty-one normotensive type 2 diabetic patients (n = 19 with and n = 22 without retinopathy) and 18 age-matched control subjects participated in the study. Serum 7 S-collagen and plasma ANP levels were measured by radioimmunoassays. Serum 7 S-collagen (4.4 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01) levels and plasma ANP (20.8 +/- 1.0 vs 15.5 +/- 1.0 pg/ml; p < 0.01) were significantly higher in diabetic patients than in normal subjects. Serum 7 S-collagen increased significantly in diabetic patients without retinopathy compared with normal subjects (4.1 +/- 0.1 vs 3.5 +/- 0.1 ng/ml; p < 0.01). Diabetic patients with retinopathy showed significantly higher circulating concentrations of 7 S-collagen (4.6 +/- 0.1 vs 4.1 +/- 0.1 ng/ml; p < 0.01) and ANP (22.9 +/- 1.4 vs 18.9 +/- 1.3 pg/ml; p < 0.05) than those without retinopathy. There was a significant and positive correlation (r = 0.51, p < 0.01) between the circulating levels of 7 S-collagen and ANP in all patients. The results of this investigation showed that increased circulating levels of ANP correlate with the abnormal metabolism of the vascular basement membrane observed in diabetic patients with microangiopathy.

Topics: Atrial Natriuretic Factor; Blood Glucose; Collagen; Diabetes Mellitus, Type 2; Diabetic Retinopathy; Female; Glycated Hemoglobin; Humans; Insulin; Lipids; Male; Middle Aged