title: Blunted renal dopaminergic system in a mouse model of diet-induced obesity.
abstract: Obesity has reached epidemic proportions in the Western world and is implicated in the pathophysiology of essential hypertension. The aim of the present study was to evaluate sodium handling, blood pressure and renal dopaminergic system activity in a mouse model of obesity induced by exposure to a hypercaloric diet. From six to 18 weeks of age, animals were fed with a control diet or a high-fat high-simple-carbohydrate (HFHSC) diet. Renal function, blood pressure and urinary and plasmatic catecholamines and biochemical parameters were evaluated in both groups. In parallel, the effects of high sodium intake (HS, 1.0% NaCl, 3 days) on natriuresis, urinary catecholamine excretion and aromatic l-amino acid decarboxylase (AADC) activity were evaluated in control and obese mice. Mice exposed to the HFHSC diet presented obesity, hyperglycemia, glucose intolerance, insulin resistance, hyperinsulinemia and increased blood pressure. This was accompanied, in obese mice, by decreases in urinary excretion of dopamine and metabolites as well as reduced AADC activity in renal tissues. During HS intake, absolute urinary dopamine excretion increased in control, but not in obese mice. This was accompanied in obese mice by a natriuretic resistance on day 1 of the HS diet. In addition, obese mice presented increased urinary and plasmatic noradrenaline levels, as well as an increased heart rate when compared with control mice. In conclusion, in this model of diet-induced obesity hyperinsulinemia, insulin resistance and increased sympathetic tone are associated with blunted renal dopaminergic activity. It is suggested that this may contribute to compromised sodium excretion and increased blood pressure in obesity.
authors.affiliation: Nephrology Research and Development Unit, University of Porto, Porto, Portugal.
authors.forename: Mónica
authors.initials: M
authors.lastname: Moreira-Rodrigues
authors.forename: Janete
authors.initials: J
authors.lastname: Quelhas-Santos
authors.forename: Roberto
authors.initials: R
authors.lastname: Roncon-Albuquerque
authors.forename: Paula
authors.initials: P
authors.lastname: Serrão
authors.forename: Adelino
authors.initials: A
authors.lastname: Leite-Moreira
authors.forename: Benedita
authors.initials: B
authors.lastname: Sampaio-Maia
authors.forename: Manuel
authors.initials: M
authors.lastname: Pestana
mesh_terms: D000818:Animals; D001142:Aromatic-L-Amino-Acid Decarboxylases / Q000378:metabolism; D002395:Catecholamines / Q000652:urine; D004032:Diet / Q000379:methods*; D015259:Dopamine Agents; D059290:Dopaminergic Neurons / Q000502:physiology*; D007668:Kidney / Q000503:physiopathology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009318:Natriuresis; D009765:Obesity / Q000139:chemically induced* / Q000503:physiopathology*; D012964:Sodium / Q000008:administration & dosage
chemical_list: D002395:Catecholamines; D015259:Dopamine Agents; D012964:Sodium; D001142:Aromatic-L-Amino-Acid Decarboxylases