Angiotensin-(1-7) prevents activation of NADPH oxidase and renal vascular dysfunction in diabetic hypertensive rats.
OBJECTIVE
We examined the influence of chronic treatment with angiotensin-(1-7) [Ang-(1-7)] on renox (renal NADPH oxidase, NOX-4) and the development of renal dysfunction in streptozotocin-treated spontaneously hypertensive rats (diabetic SHR).


METHODS
Mean arterial pressure, urinary protein and vascular responsiveness of the isolated renal artery to vasoactive agonists were studied in vehicle- or Ang-(1-7)-treated SHR and diabetic SHR.


RESULTS
Ang-(1-7) decreased the elevated levels of renal NADPH oxidase (NOX) activity and attenuated the activation of NOX-4 gene expression in the diabetic SHR kidney. Ang-(1-7) treatment increased sodium excretion but did not affect mean arterial pressure in diabetic SHR. There was a significant increase in urinary protein (266 +/- 22 mg/24 h) in the diabetic compared to control SHR (112 +/- 13 mg/24 h) and treatment of diabetic SHR with Ang-(1-7) reduced the degree of proteinuria (185 +/- 23 mg/24 h, p < 0.05). Ang-(1-7) treatment also attenuated the diabetes-induced increase in renal vascular responsiveness to endothelin-1, norepinephrine, and angiotensin II in SHR, but significantly increased the vasodilation of the renal artery of SHR and diabetic SHR to the vasodilator agonists.


CONCLUSIONS
These results suggest that treatment with Ang-(1-7) constitutes a potential therapeutic strategy to alleviate NOX-mediated oxidative stress and to reduce renal dysfunction in diabetic hypertensive rats.
Benter
Ibrahim F
IF
Department of Pharmacology and Toxicology, Faculty of Medicine, Kuwait University, Kuwait. ibenter@hsc.edu.kw
Yousif
Mariam H M
MH
Dhaunsi
Gursev S
GS
Kaur
Jaspal
J
Chappell
Mark C
MC
Diz
Debra I
DI
D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001835:Body Weight; D003921:Diabetes Mellitus, Experimental / Q000150:complications; D003928:Diabetic Nephropathies / Q000150:complications / Q000188:drug therapy* / Q000503:physiopathology; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006943:Hyperglycemia / Q000150:complications; D006977:Hypertension, Renal / Q000188:drug therapy* / Q000209:etiology / Q000503:physiopathology; D008297:Male; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases / Q000235:genetics / Q000378:metabolism*; D010446:Peptide Fragments / Q000494:pharmacology*; D011507:Proteinuria / Q000150:complications / Q000188:drug therapy / Q000503:physiopathology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012079:Renal Circulation / Q000187:drug effects; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000959:Antihypertensive Agents; D010446:Peptide Fragments; D000803:Angiotensin I; D000074663:NADPH Oxidase 4; D019255:NADPH Oxidases; C498911:Nox4 protein, rat; C118790:angiotensin I (1-7)