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Knockdown of Add3 impairs the myogenic response of renal afferent arterioles and middle cerebral arteries.

Authors: Fan, Fan  Pabbidi, Mallikarjuna R  Ge, Ying  Li, Longyang  Wang, Shaoxun  Mims, Paige N  Roman, Richard J 
Citation: Fan F, etal., Am J Physiol Renal Physiol. 2017 Jun 1;312(6):F971-F981. doi: 10.1152/ajprenal.00529.2016. Epub 2016 Dec 7.
Pubmed: (View Article at PubMed) PMID:27927653
DOI: Full-text: DOI:10.1152/ajprenal.00529.2016

We have reported that the myogenic response of the renal afferent arteriole (Af-art) and middle cerebral artery (MCA) and autoregulation of renal and cerebral blood flow are impaired in Fawn-Hooded Hypertensive (FHH) rats. Transfer of a region of chromosome 1 containing γ-adducin (Add3) from the Brown Norway rat rescued the vascular dysfunction and the development of renal disease. To examine whether Add3 is a viable candidate gene altering renal and cerebral hemodynamics in FHH rats, we knocked down the expression of Add3 in rat Af-arts and MCAs cultured for 36-h using a 27-mer Dicer-substrate short interfering RNA (DsiRNA). Control Af-arts constricted by 10 ± 1% in response to an elevation in pressure from 60 to 120 mmHg but dilated by 4 ± 3% when treated with Add3 DsiRNA. Add3 DsiRNA had no effect on the vasoconstrictor response of the Af-art to norepinephrine (10(-7) M). Add3 DsiRNA had a similar effect on the attenuation of the myogenic response in the MCA. Peak potassium currents were threefold higher in smooth muscle cells isolated from Af-arts or MCAs transfected with Add3 DsiRNA than in nontransfected cells isolated from the same vessels. This is the first study demonstrating that Add3 plays a role in the regulation of potassium channel function and vascular reactivity. It supports the hypothesis that sequence variants in Add3, which we previously identified in FHH rats, may play a causal role in the impaired myogenic response and autoregulation in the renal and cerebral circulation.


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RGD Object Information
RGD ID: 13446409
Created: 2017-11-07
Species: All species
Last Modified: 2017-11-07
Status: ACTIVE


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