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      Transient Receptor Potential Vanilloid 4 Channels are Important Regulators of Parenchymal Arteriole Dilation and Cognitive Function

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          Abstract

          Objective:

          Hypertension-associated parenchymal arteriole (PA) dysfunction reduces cerebral perfusion and impairs cognition. This is associated with impaired TRPV4-mediated PA dilation; therefore, we tested the hypothesis that TRPV4 channels are important regulators of cerebral perfusion, PA structure and dilation, and cognition.

          Methods:

          10–12-month-old male TRPV4 knockout (WKY- Trpv4 em4Mcwi ) and age-matched control WKY rats were studied. Cerebral perfusion was measured by MRI with arterial spin labeling. PA structure and function were assessed using pressure myography and cognitive function using the novel object recognition test.

          Results:

          Cerebral perfusion was reduced in the WKY- Trpv4 em4Mcwi rats. This was not a result PA remodeling because TRPV4 deletion did not change PA structure. TRPV4 deletion did not change PA myogenic tone development, but PAs from the WKY- Trpv4 em4Mcwi rats had severely blunted endothelium-dependent dilation. The WKY- Trpv4 em4Mcwi rats had impaired cognitive function and exhibited depressive-like behavior. The WKY- Trpv4 em4Mcwi rats also had increased microglia activation, and increased mRNA expression of GFAP and tumor necrosis factor alpha suggesting increased inflammation.

          Conclusion:

          Our data indicate that TRPV4 channels play a critical role in cerebral perfusion, PA dilation, cognition and inflammation. Impaired TRPV4 function in diseases such as hypertension may increase the risk for the development of vascular dementia.

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          Author and article information

          Journal
          9434935
          8801
          Microcirculation
          Microcirculation
          Microcirculation (New York, N.Y. : 1994)
          1073-9688
          1549-8719
          10 February 2019
          22 February 2019
          August 2019
          01 August 2020
          : 26
          : 6
          : e12535
          Affiliations
          [1 ]Department of Pharmacology and Toxicology, Michigan State University, East Lansing, MI 48824
          [2 ]Department of Physiology, Michigan State University, East Lansing, MI 48824
          [3 ]Department of Radiology, Michigan State University, East Lansing, MI 48824
          Author notes
          Correspondence: Janice M. Diaz-Otero, Department of Pharmacology and Toxicology, 1355 Bogue Street B340, Michigan State University, East Lansing, MI, 48824, diazjani@ 123456msu.edu , Phone 517 432 2133, Fax 517 353 8915
          Author information
          http://orcid.org/0000-0003-2099-2089
          http://orcid.org/0000-0002-9657-0141
          http://orcid.org/0000-0001-6573-2729
          Article
          PMC6682474 PMC6682474 6682474 nihpa1011162
          10.1111/micc.12535
          6682474
          30721555
          93b5b171-35e9-4872-89cb-74dc1fe93bd5
          History
          Categories
          Article

          endothelium-dependent dilation,trpv4 channels,microcirculation,vascular dementia

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