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

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 dependently 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 (N(omega)-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 AT1 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.