Angiotensin-(1–7) prevents diabetes-induced attenuation in PPAR-γ and catalase activities

• Published in: European journal of pharmacology Vol. 638; no. 1; pp. 108 - 114
• Main Authors: Dhaunsi, Gursev S., Yousif, Mariam H.M., Akhtar, Saghir, Chappell, Mark C., Diz, Debra I., Benter, Ibrahim F.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 25.07.2010; Elsevier
• Subjects: Acetophenones - administration & dosage; Acetophenones - pharmacology; Angiotensin; Angiotensin I - administration & dosage; Angiotensin I - pharmacology; Animals; Antihypertensive Agents - administration & dosage; Antihypertensive Agents - pharmacology; Antioxidants - administration & dosage; Antioxidants - pharmacology; Arterial hypertension. Arterial hypotension; Biological and medical sciences; Blood and lymphatic vessels; Blood Glucose - drug effects; Blood Pressure - drug effects; Cardiology. Vascular system; Catalase - metabolism; Diabetes; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - metabolism; Diabetes. Impaired glucose tolerance; Endocrine pancreas. Apud cells (diseases); Endocrinopathies; Endothelin-1 - antagonists & inhibitors; Etiopathogenesis. Screening. Investigations. Target tissue resistance; Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) - metabolism; Hyperglycemia - drug therapy; Hypertension; Hypertension - complications; Hypertension - drug therapy; Hypertension - metabolism; Hypertension - physiopathology; Kidney; Kidney - drug effects; Kidney - metabolism; Kidney - physiopathology; Male; Medical sciences; NADPH Oxidases - metabolism; Peptide Fragments - administration & dosage; Peptide Fragments - pharmacology; Pharmacology. Drug treatments; PPAR gamma - metabolism; Proteinuria - drug therapy; Rats; Rats, Inbred SHR; Rats, Inbred WKY; Renal Artery - drug effects; Hypertension; Diabetes; Kidney; Angiotensin; Endocrinopathy; Enzyme; Diabetes mellitus; Cardiovascular disease; PPAR-γ receptor; Renin angiotensin system; Urinary system; Peroxidases; Catalase; Oxidoreductases
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2010.04.030

The mechanisms by which angiotensin-(1–7) [Ang-(1–7)] exerts its beneficial effects on end-organ damage associated with diabetes and hypertension are not well understood. The purpose of this study was A) to compare the effects of apocynin with Ang-(1–7) on renal vascular dysfunction and NADPH oxidase activity in a combined model of diabetes and hypertension and B) to further determine whether chronic treatment with Ang-(1–7) can modulate renal catalase, and peroxisome proliferator activated receptor- γ (PPAR-γ) levels in streptozotocin-induced diabetes in both normotensive Wistar Kyoto rats (WKY) and in spontaneously hypertensive rats (SHR). Apocynin or Ang-(1–7) treatment for one month starting at the onset of diabetes similarly attenuated elevation of renal NADPH oxidase activity in the diabetic SHR kidney and reduced the degree of proteinuria and hyperglycemia, but had little or modest effect on reducing mean arterial pressure. Both drugs also attenuated the diabetes-induced increase in renal vascular responsiveness to endothelin-1. Induction of diabetes in WKY and SHR animals resulted in significantly reduced renal catalase activity and in PPAR-γ mRNA and protein levels. Treatment with Ang-(1–7) significantly prevented diabetes-induced reduction in catalase activity and the reduction in PPAR-γ mRNA and protein levels in both animal models. Taken together, these data suggest that activation of Ang-(1–7)-mediated signaling could be an effective way to prevent the elevation of NADPH oxidase activity and inhibition of PPAR-γ and catalase activities in diabetes and/or hypertension.