Knockdown of Add3 impairs the myogenic response of renal afferent arterioles and middle cerebral arteries.
Am J Physiol Renal Physiol
; 312(6): F971-F981, 2017 06 01.
Article
em En
| MEDLINE
| ID: mdl-27927653
ABSTRACT
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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MEDLINE
Assunto principal:
Vasoconstrição
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Proteínas de Ligação a Calmodulina
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Interferência de RNA
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Técnicas de Silenciamento de Genes
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Hipertensão
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Rim
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Músculo Liso Vascular
Limite:
Animals
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article