ArticlePloS one2014
Zinc-finger nuclease knockout of dual-specificity protein phosphatase-5 enhances the myogenic response and autoregulation of cerebral blood flow in FHH.1BN rats.
Article in PloS one, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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34 citing papers in PubMed, 47 citations in OpenAlex.
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- Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5.Journal of pharmacy and pharmacology research · 2023Article
- Luseogliflozin, a sodium-glucose cotransporter-2 inhibitor, reverses cerebrovascular dysfunction and cognitive impairments in 18-mo-old diabetic animals.American journal of physiology. Heart and circulatory physiology · 2022Article
- The adducin saga: pleiotropic genomic targets for precision medicine in human hypertension-vascular, renal, and cognitive diseases.Physiological genomics · 2022Review
- Impact of impaired cerebral blood flow autoregulation on cognitive impairment.Frontiers in aging · 2022Review
- 20-HETE-promoted cerebral blood flow autoregulation is associated with enhanced pericyte contractility.Prostaglandins & other lipid mediators · 2021Article
- Role of γ-adducin in actin cytoskeleton rearrangements in podocyte pathophysiology.American journal of physiology. Renal physiology · 2021Article
- Genetic susceptibility of hypertension-induced kidney disease.Physiological reports · 2021Review
- Aging exacerbates impairments of cerebral blood flow autoregulation and cognition in diabetic rats.GeroScience · 2020Article
- Rat models of human diseases and related phenotypes: a systematic inventory of the causative genes.Journal of biomedical science · 2020Review
- Sex differences in the structure and function of rat middle cerebral arteries.American journal of physiology. Heart and circulatory physiology · 2020Article
- A Mutation inJournal of the American Society of Nephrology : JASN · 2020Article
- Accelerated cerebral vascular injury in diabetes is associated with vascular smooth muscle cell dysfunction.GeroScience · 2020Article
- Duration and magnitude of bidirectional fluctuation in blood pressure: the link between cerebrovascular dysfunction and cognitive impairment following spinal cord injury.Journal of neurobiology and physiology · 2020Article
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7 authors at 2 institutions in 1 country.
Funding
Abstract
We recently reported that the myogenic responses of the renal afferent arteriole (Af-Art) and middle cerebral artery (MCA) and autoregulation of renal and cerebral blood flow (RBF and CBF) were impaired in Fawn Hooded hypertensive (FHH) rats and were restored in a FHH.1BN congenic strain in which a small segment of chromosome 1 from the Brown Norway (BN) containing 15 genes including dual-specificity protein phosphatase-5 (Dusp5) were transferred into the FHH genetic background. We identified 4 single nucleotide polymorphisms in the Dusp5 gene in FHH as compared with BN rats, two of which altered CpG sites and another that caused a G155R mutation. To determine whether Dusp5 contributes to the impaired myogenic response in FHH rats, we created a Dusp5 knockout (KO) rat in the FHH.1BN genetic background using a zinc-finger nuclease that introduced an 11 bp frame-shift deletion and a premature stop codon at AA121. The expression of Dusp5 was decreased and the levels of its substrates, phosphorylated ERK1/2 (p-ERK1/2), were enhanced in the KO rats. The diameter of the MCA decreased to a greater extent in Dusp5 KO rats than in FHH.1BN and FHH rats when the perfusion pressure was increased from 40 to 140 mmHg. CBF increased markedly in FHH rats when MAP was increased from 100 to 160 mmHg, and CBF was better autoregulated in the Dusp5 KO and FHH.1BN rats. The expression of Dusp5 was higher at the mRNA level but not at the protein level and the levels of p-ERK1/2 and p-PKC were lower in cerebral microvessels and brain tissue isolated from FHH than in FHH.1BN rats. These results indicate that Dusp5 modulates myogenic reactivity in the cerebral circulation and support the view that a mutation in Dusp5 may enhance Dusp5 activity and contribute to the impaired myogenic response in FHH rats.
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