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High Fat Feeding Reduces Cerebral Artery Transient Receptor Potential Channel Vanilloid 4 (TRPV4) Expression In A Mineralocorticoid Receptor‐Dependent Manner
Author(s) -
Dorrance Anne McLaren,
DiazOtero Janice,
Pires Paulo W,
Jackson William F
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.836.12
Subject(s) - transient receptor potential channel , medicine , endocrinology , trpv4 , mineralocorticoid receptor , cerebral arteries , population , aldosterone , receptor , environmental health
Overweight/obese patients are at an increased risk of developing cognitive impairment associated with chronic cerebral hypoperfusion. We have developed an overweight rat model that exhibits impaired cerebral artery endothelial function and cognitive decline. The mechanisms responsible for the impaired cerebral artery dilation have not been determined. Recent studies from our laboratory have identified the transient receptor potential channel (TRP) vanilloid 4 (TRPV4) as a key regulator of cerebral artery endothelium‐dependent dilation. We therefore hypothesized that TRPV4 mRNA expression would be reduced in cerebral arteries from overweight rats. Cerebral arteries were collected from overweight rats fed a high fat (HF) diet for 17 weeks from 3 weeks of age; these were compared to arteries from control chow fed rats (n=5 in each group). qRT‐PCR with TAQMAN primers was used to assess TRPV4 expression, TRPV3 and TRPA1 expression were also assessed. HF feeding specifically reduced TRPV4 mRNA expression (fold change from control = 0.58±0.11; p<0.01), while it had no effect on TRPV3 (fold change from control = 1.144±0.28; p=0.6) or TRPA1 (fold change from control = 1.08±0.2; p=0.7) mRNA expression. Circulating levels of aldosterone are increased in the overweight population, to test if this plays a role in the reduced TRPV4 expression observed with HF feeding we treated rats with the mineralocorticoid receptor (MR) antagonist canrenoic acid (CAN 20mg/kg/day n=3) for the duration of the HF feeding, these were compared to placebo treated HF fed rats (n=5). MR antagonism increased the mRNA expression of TRPV4 (fold change from HF placebo treated = 2.012±0.24; p<0.01). CAN treatment also increased the expression of doublecortin, a marker of new and immature neurons (fold change from HF placebo treated = 2.184±0.37; p<0.01) and synaptophysin a marker of synapse formation (fold change from HF placebo treated = 2.90±1.05; p<0.01). Taken together these studies suggest the MR antagonism improves expression of TRPV4, a key regulator of cerebral artery dilation. Augmented expression of TRPV4 may improve cerebral perfusion, and may reduce the cognitive decline observed in the overweight population. Support or Funding Information Supported by 5P01HL070687‐12.