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Angiotensin II modulates renal sympathetic neurotransmission through nitric oxide in AT2 receptor knockout mice

Item Type:Article
Title:Angiotensin II modulates renal sympathetic neurotransmission through nitric oxide in AT2 receptor knockout mice
Creators Name:Stegbauer, J. and Vonend, O. and Habbel, S. and Quack, I. and Sellin, L. and Gross, V. and Rump, L.C.
Abstract:Objective: Angiotensin (Ang) II enhances renal sympathetic neurotransmission and stimulates nitric oxide (NO) release. The present study investigates whether Ang II-mediated modulation of sympathetic neurotransmission is dependent on NO production in the kidney. AT2 -/y receptor-deficient mice are used to identify the Ang II receptor subtype involved. Methods: Mice kidneys were isolated and perfused with Krebs-Henseleit solution. Drugs were added to the perfusion solution in a cumulative manner. Release of endogenous noradrenaline (NA) was measured by high-performance liquid chromatography (HPLC). AT1 receptor expression was analysed by real-time polymerase chain reaction (PCR). Results: Ang II (0.01 - 30 nmol/l) dose dependency increased pressor responses in kidneys of AT2 -/y mice and wild-type (AT2 +/y) mice. Maximal pressor responses and EC50 values for Ang II was greater in AT2 -/y than in AT2 +/y mice. L-NAME (Nω-nitro-L-arginine methyl ester; 0.3 mmol/l) enhanced Ang II-induced pressor responses in both strains. In AT2 -/y mice, Ang II-induced facilitation of NA release was more pronounced than in AT2 +/y mice. L-NAME reduced Ang II-mediated facilitation of NA release in both strains. This reduction was more potent in AT2 -/y mice. In kidneys of AT2 -/y mice the AT 1 receptor expression was significantly upregulated. Conclusion: These results suggest that activation of AT1 receptors by Ang II releases NO in mouse kidney to modulate sympathetic neurotransmission. Since AT1 receptors are upregulated in AT2 -/y mice kidneys, NO-dependent effects were greater in these mice. Thus, NO seems to play an important modulatory role for renal sympathetic neurotransmission.
Keywords:Angiotensin, Nitric oxide, Noradrenaline, Receptor, Receptor deficient mouse, Sympathetic neurotransmission, Animals, Mice
Source:Journal of Hypertension
Publisher:Lippincott Williams & Wilkins
Page Range:1691-1698
Date:1 January 2005
PubMed:View item in PubMed

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