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. 2011 Sep 8;2(6):1000135.
doi: 10.4172/2155-6156.1000135.

Elevated angiotensin II in rat nodose ganglia primes diabetes-blunted arterial baroreflex sensitivity: involvement of NADPH oxidase-derived superoxide

Yu-Long Li  1
Affiliations

Elevated angiotensin II in rat nodose ganglia primes diabetes-blunted arterial baroreflex sensitivity: involvement of NADPH oxidase-derived superoxide

Yu-Long Li. J Diabetes Metab. .

Abstract

Clinical trials and experimental animal studies have confirmed the contribution of arterial baroreflex impairment in causing excess morbidity and mortality in type-1 diabetes. Our previous study has shown that angiotensin II (Ang II)-NADPH oxidase-superoxide signaling is associated with the reduced cell excitability in the aortic baroreceptor neurons (a primary afferent limb of the arterial baroreflex) from diabetic rats. In this study, we examined whether above-mentioned signaling might contribute to the blunted baroreflex sensitivity in streptozotocin-induced diabetic rats. Using Ang II (125)I radioimmunoassay and lucigenin chemiluminescence method, we found Ang II concentration, NADPH oxidase activity, and superoxide production in the nodose ganglia were enhanced in diabetic rats, compared to sham rats. As an index of the arterial baroreflex sensitivity, the reflex decreases in blood pressure and heart rate evoked by unilateral steady-frequency aortic depressor nerve stimulation were attenuated in diabetic rats. Local microinjection (50 nl) of losartan (an AT(1) receptor antagonist, 1 nmol), apocynin (a NADPH oxidase inhibitor, 1 nmol), and tempol (a superoxide dismutase mimetic, 10 nmol) into the nodose ganglia significantly improved the arterial baroreflex sensitivity in diabetic rats. In addition, these three chemicals also normalized exogenous Ang II-attenuated arterial baroreflex sensitivity in sham rats. These results indicate that overactivation of the Ang II-NADPH oxidase-superoxide signal pathway in the nodose ganglia contributes to the blunted baroreflex sensitivity in diabetes.

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Figures

Figure 1
Figure 1
Angiotensin II concentration, NADPH oxidase activity, and superoxide production in sham and STZ-induced diabetic rats. Apocynin (a NADPH oxidase inhibitor, 100 µM) and tempol (a superoxide dismutase mimetic, 1 mM) were used to confirm the specificity of the measurement for NADPH oxidase and superoxide production respectively. Data are mean ± SE, n=6 rats in each group. *P<0.05 vs. sham rats; #p<0.05 vs. diabetes.
Figure 2
Figure 2
Representative tracings of blood pressure and heart rate responses to aortic depressor nerve (ADN) stimulation in sham and STZ-induced diabetic rats. ABP, arterial blood pressure; MBP, mean blood pressure; HR, heart rate.
Figure 3
Figure 3
Effects of losartan, apocynin, and tempol on the arterial baroreflex sensitivity in STZ-induced diabetic rats. A, reflex ΔMAP and ΔHR in response to different frequencies of ADN stimulation in sham and diabetic rats. B, reflex ΔMAP and ΔHR in response to ADN stimulation (100 Hz) in each group (chemicals were microinjected into the nodose ganglion). Data are mean ± SE, n=6 rats in each group. *P<0.05 vs. sham rats; #p<0.05 vs. diabetic rats.
Figure 4
Figure 4
Effects of exogenous Ang II on the arterial baroreflex sensitivity in sham rats. A, reflex ΔMAP and ΔHR in response to different frequencies of ADN stimulation before and after local microinjection of Ang II into the nodose ganglia in sham rats. B, reflex ΔMAP and ΔHR in response to ADN stimulation (100 Hz) in each group. Data are mean ± SE, n=6 rats in each group. *P<0.05 vs. control without Ang II; #p<0.05 vs. control with Ang II.
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