Synergistic Interaction of Hypertension and Diabetes in Promoting Kidney Injury and the Role of Endoplasmic Reticulum Stress
| Autor: | Jussara M. do Carmo, Jan M. Williams, Zhen Wang, John E. Hall, Alexandre A. da Silva, Nicola Aberdein, Xinchun Zhou |
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| Rok vydání: | 2017 |
| Předmět: |
Blood Glucose
Male 0301 basic medicine medicine.medical_specialty Renal function Blood Pressure 030204 cardiovascular system & hematology Kidney medicine.disease_cause Article 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Internal medicine Diabetes mellitus Internal Medicine medicine Animals Rats Wistar Renal Insufficiency Chronic business.industry Tauroursodeoxycholic acid Endoplasmic Reticulum Stress medicine.disease Rats Oxidative Stress 030104 developmental biology Endocrinology Blood pressure medicine.anatomical_structure Diabetes Mellitus Type 2 chemistry Hypertension Unfolded protein response business Oxidative stress Hormone |
| Zdroj: | Hypertension. 69:879-891 |
| ISSN: | 1524-4563 0194-911X |
| Popis: | Diabetes mellitus and hypertension are major risk factors for chronic kidney injury, together accounting for >70% of end-stage renal disease. In this study, we assessed interactions of hypertension and diabetes mellitus in causing kidney dysfunction and injury and the role of endoplasmic reticulum (ER) stress. Hypertension was induced by aorta constriction (AC) between the renal arteries in 6-month-old male Goto-Kakizaki (GK) type 2 diabetic and control Wistar rats. Fasting plasma glucose averaged 162±11 and 87±2 mg/dL in GK and Wistar rats, respectively. AC produced hypertension in the right kidney (above AC) and near normal blood pressure in the left kidney (below AC), with both kidneys exposed to the same levels of glucose, circulating hormones, and neural influences. After 8 weeks of AC, blood pressure above the AC (and in the right kidney) increased from 109±1 to 152±5 mm Hg in GK rats and from 106±4 to 141±5 mm Hg in Wistar rats. The diabetic-hypertensive right kidneys in GK–AC rats had much greater increases in albumin excretion and histological injury compared with left kidneys (diabetes mellitus only) of GK rats or right kidneys (hypertension only) of Wistar–AC rats. Marked increases in ER stress and oxidative stress indicators were observed in diabetic-hypertensive kidneys of GK–AC rats. Inhibition of ER stress with tauroursodeoxycholic acid for 6 weeks reduced blood pressure (135±4 versus 151±4 mm Hg), albumin excretion, ER and oxidative stress, and glomerular injury, while increasing glomerular filtration rate in hypertensive-diabetic kidneys. These results suggest that diabetes mellitus and hypertension interact synergistically to promote kidney dysfunction and injury via ER stress. |
| Databáze: | OpenAIRE |
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