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Angiotensin II‐mediated sympathoexcitation in diabetes: Role of superoxide
Author(s) -
Zheng Hong,
Liu Xuefei,
Kleiber Allison,
Davisson Robin L,
Patel Kaushik P.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.5.a1208-a
Subject(s) - endocrinology , medicine , superoxide , angiotensin ii , angiotensin ii receptor type 1 , rostral ventrolateral medulla , streptozotocin , diabetes mellitus , microinjection , superoxide dismutase , chemistry , stimulation , nadph oxidase , receptor , oxidative stress , blood pressure , heart rate , enzyme , biochemistry
Our previous study has demonstrated an enhanced angiotensin II (Ang II) mediated sympathoexcitation in diabetes. Recent studies have shown that a superoxide mechanism is involved in Ang II signaling in the central nervous system. We hypothesized that Ang II activates sympathetic outflow by stimulation of superoxide within the PVN of diabetic rats. In a‐chloralose and urethane anesthetized rats, microinjection of Ang II into the PVN (50, 100 and 200pmol) produced dose‐dependent increases in renal sympathetic nerve activity (RSNA), arterial pressure (AP) and heart rate (HR) in control rats and streptozotocin (STZ)‐induced diabetic rats. There was a potentiation of the increase in RSNA (27.7±2.1% vs. 19.1±1.1%, P<0.05), AP and HR due to Ang II AT1 receptor activation in diabetic rats compared to control rats. These potentiated responses were attenuated by pretreatment with adenoviral vector‐mediated over‐expression of human mitochondrial superoxide dismutase (AdMnSOD) within the PVN of the diabetic rats (RSNA 20.4±0.7% vs. 27.7±2.1%, n=6, P<0.05). In addition, significant increases in mRNA and protein expression of NAD(P)H oxidase subunits p22phox, p47phox and p67phox in the PVN were observed in diabetic rats. p47phox mRNA expression increased 36.0±4.0% and p47phox protein level increased 31.1±1.7% (n=6, P<0.05). These data support the conclusion that superoxide contributes to enhanced Ang II‐mediated signaling in the PVN involved with the exaggerated sympathoexcitation in diabetes.