Angiotensin-(1-7) prevents diabetes-induced attenuation in PPAR-gamma and catalase activities.
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- gamma (PPAR-gamma) 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-gamma mRNA and protein levels. Treatment with Ang-(1-7) significantly prevented diabetes-induced reduction in catalase activity and the reduction in PPAR-gamma 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-gamma and catalase activities in diabetes and/or hypertension.
Dhaunsi
Gursev S
GS
Department of Pediatrics, Faculty of Medicine, Kuwait University, Kuwait.
Yousif
Mariam H M
MH
Akhtar
Saghir
S
Chappell
Mark C
MC
Diz
Debra I
DI
Benter
Ibrahim F
IF
D000098:Acetophenones / Q000008:administration & dosage / Q000494:pharmacology; D000803:Angiotensin I / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D001786:Blood Glucose / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002374:Catalase / Q000378:metabolism*; D003921:Diabetes Mellitus, Experimental / Q000150:complications / Q000188:drug therapy / Q000378:metabolism*; D019332:Endothelin-1 / Q000037:antagonists & inhibitors; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating) / Q000378:metabolism; D006943:Hyperglycemia / Q000188:drug therapy; D006973:Hypertension / Q000150:complications / Q000188:drug therapy / Q000378:metabolism / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D008297:Male; D019255:NADPH Oxidases / Q000378:metabolism; D047495:PPAR gamma / Q000378:metabolism*; D010446:Peptide Fragments / Q000008:administration & dosage / Q000494:pharmacology*; D011507:Proteinuria / Q000188:drug therapy; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012077:Renal Artery / Q000187:drug effects
D000098:Acetophenones; D000959:Antihypertensive Agents; D000975:Antioxidants; D001786:Blood Glucose; D019332:Endothelin-1; D047495:PPAR gamma; D010446:Peptide Fragments; D000803:Angiotensin I; C056165:acetovanillone; D002374:Catalase; D024581:Glyceraldehyde-3-Phosphate Dehydrogenase (Phosphorylating); D019255:NADPH Oxidases; C118790:angiotensin I (1-7)
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