RGD Reference Report - Different blood pressure responses in hypertensive rats following chemerin mRNA inhibition in dietary high fat compared to dietary high-salt conditions.

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Different blood pressure responses in hypertensive rats following chemerin mRNA inhibition in dietary high fat compared to dietary high-salt conditions.
Authors:	Ferland, David J Flood, Emma D Garver, Hannah Yeh, Steve T Riney, Stanley Mullick, Adam E Fink, Gregory D Watts, Stephanie W
Citation:	Ferland DJ, etal., Physiol Genomics. 2019 Nov 1;51(11):553-561. doi: 10.1152/physiolgenomics.00050.2019. Epub 2019 Oct 7.
RGD ID:	15036819
Pubmed:	PMID:31588871 (View Abstract at PubMed)
PMCID:	PMC6879813 (View Article at PubMed Central)
DOI:	DOI:10.1152/physiolgenomics.00050.2019 (Journal Full-text)
Chemerin is a contractile adipokine, produced in liver and fat, and removal of the protein by antisense oligonucleotides (ASO) lowers blood pressure in the normal Sprague Dawley rat. In humans, chemerin is positively associated with blood pressure and obesity so we hypothesized that in a model of hypertension derived from high-fat (HF) feeding, the chemerin ASO would reduce blood pressure more than a high-salt (HS) model. Male Dahl S rats were given a HF (60% kcal fat; age 3-24 wk) or HS diet (4% salt; age 20-24 wk to match age and blood pressure of HF animals). Scrambled control, whole body, or liver-specific ASOs that knock down chemerin were delivered subcutaneously once per week for 4 wk with tissue and blood collected 2 days after the last injection. Conscious blood pressure was measured 24 h/day by radiotelemetry. By the end of whole body ASO administration, blood pressure of HF animals had fallen 29 ± 2 mmHg below baseline, while blood pressure of HS-diet animals fell by only 12 ± 4 mmHg below baseline. Administration of a liver-specific ASO to HF Dahl S resulted in a 6 ± 2 mmHg fall in blood pressure below baseline. Successful knockdown of chemerin in both the whole body and liver-specific administration was confirmed by Western and PCR. These results suggest that chemerin, not derived from liver but potentially from adipose tissue, is an important driver of hypertension associated with high fat. This knowledge could lead to the development of antihypertensive treatments specifically targeted to obesity-associated hypertension.

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Object Symbol	Species	Term	Qualifier	Evidence	With	Notes	Source	Original Reference(s)
Rarres2	Rat	positive regulation of systemic arterial blood pressure		IMP			RGD

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Rarres2	Rat	extracellular space		IDA		MMO:0000669	RGD

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Genes (Rattus norvegicus)

Rarres2 (retinoic acid receptor responder 2)

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Different blood pressure responses in hypertensive rats following chemerin mRNA inhibition in dietary high fat compared to dietary high-salt conditions.