High Sodium Diet in 11β Hydroxysteroid Dehydrogenase Type 2 CNS Knockout Mice Induces a Proinflammatory Phenotype of Perivascular Adipose Tissue and Alterations in Arterial Reactivity

Abstract

RationaleWe previously generated CNS‐specific knockout of HSD2 (“brain” knockout; BKO), showing that the mice have inappropriate salt‐appetite and hypertension under a high sodium diet (Evans, Ivy et al. 2016) . Multiple peripheral components may contribute to this salt‐sensitivity and here we have focussed on the role of resistance arteries, which are surrounded by perivascular adipose tissue (PVAT), able to secrete vasoactive molecules (pro‐ or anticontractile). It is well known that PVAT interacts with arteries to regulate their function. Studies also show that high‐sodium diet stimulates adipocity and alters adipocyte function. Our aim is to study the impact of high sodium intake on PVAT gene expression and on arterial reactivity in BKO knockout mice.MethodsBKO mice were generated by crossing HSD2flx/flx with Nestin‐Cre mice; HSD2flx/flx littermates were used as wild‐type controls (WT). Mice were fed with high sodium diet (HSD; 3% Na) or normal sodium diet (NSD; 0.3% Na) for one week before being culled. The PVAT and the mesenteric arteries were dissected. The arterial reactivity to phenylephrine (Phe), acetyl choline (Ach) and sodium nitroprusside (SNP) was studied by wire myography. In PVAT from mesenteric arteries, the expression of a panel of pro or anti inflammatory markers was measured by qRT‐PCR.ResultsOn normal sodium diet, There was no difference between genotypes in the PVAT expression of a panel of genes reporting inflammation (adipoq, lep, cybb, ptgs2, agtr1a, serpin, pparg, il‐6, ccl2, adgre1, vcam1, atp6ap2, nampt). High sodium diet demonstrated a significant (all P<0.05) overexpression of the proinflammatory genes il‐6, ccl2, cybb and ptgs2 on BKO fed with HSD compared to WT; other genes were not different. In PVAT‐free mesenteric arteries, hsd11b2 gene expression was not different between WT and BKO mesenteric arteries and on normal sodium diet, arterial reactivity to Phe, Ach and SNP was not different between genotypes. In contrast, 7 days of high sodium intake revealed there were differences in arterial function between genotypes: there was a significant increase in sensitivity to Phe in the WT and a decrease of the maximum effect of SNP in the BKO mice.ConclusionThe high salt diet on BKO mice led to an overexpression in pro‐inflammatory gene in the PVAT surrounding mesenteric arteries and affected intrinsic arterial reactivity. The interaction between these two phenomena remains to be elucidated but it may contribute explanation to the increase of blood pressure of salt sensitive BKO mice.Support or Funding InformationThis work was funded by The British Heart Foundation (PG/16/98/32568)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.