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Angiotensin II type 2 receptor-mediated inhibition of norepinephrine release in isolated rat hearts.

Authors: Sasaoka, T  Egi, Y  Tawa, M  Yamamoto, A  Ohkita, M  Takaoka, M  Maruyama, T  Akira, T  Matsumura, Y 
Citation: Sasaoka T, etal., J Cardiovasc Pharmacol. 2008 Aug;52(2):176-83.
Pubmed: (View Article at PubMed) PMID:18670361
DOI: Full-text: DOI:10.1097/FJC.0b013e31818127f8

We investigated whether endogenous and exogenous angiotensin II (Ang II) regulates norepinephrine (NE) release from cardiac sympathetic nerves via both Ang II type 2 receptors (AT2Rs) and Ang II type 1 receptors (AT1Rs). Using isolated rat hearts, sympathetic nerves were electrically stimulated. Ang II with PD-123319 (AT2R antagonist) but not Ang II alone produced a significant increase in nerve stimulation-induced NE overflow, which was abolished by the addition of AT1R antagonist losartan. In contrast, NE overflow was markedly decreased by losartan with or without Ang II. This decrease was abolished by the combination with PD-123319, nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine (NOARG), icatibant (bradykinin B2 receptor antagonist), or PKSI-527 (kininogenase inhibitor). CGP-42112A (AT2R agonist) suppressed nerve stimulation-induced NE overflow in the same way as the combination of Ang II and losartan, and this suppression was abolished by PD-123319, NOARG, icatibant, or PKSI-527. There were significant increases in NOx (NO2/NO3) contents in coronary effluent under conditions where NE overflow was suppressed. Ang II seems to function as an inhibitory modulator of cardiac noradrenergic neurotransmission via AT2Rs and well-known AT1R-mediated stimulatory actions. The inhibitory mechanism may involve local bradykinin production, its B2 receptor activation, and NO as a downstream effector.

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RGD Object Information
RGD ID: 6903961
Created: 2012-10-09
Species: All species
Last Modified: 2012-10-09
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.