< em > In utero < /em > exposure to maternal diabetes exacerbates dietary sodium intake-induced endothelial dysfunction by activating cyclooxygenase 2-derived proteinoids

Am J Physiol Endocrinol Metab. 2024 Mar 6. doi: 10.1152/ajpendo.00009.2024. Online ahead of print.ABSTRACTPrenatal exposure to maternal diabetes has been identified as a cardiovascular risk factor. It is unclear if offspring exposed to diabetes in utero manifest a worse vascular outcome to a high salt (HS) diet. To test the hypothesis that in utero exposure to maternal diabetes facilitates salt-induced vascular dysfunction, we treated adult male wild-type offspring (DM_Exp, 6-months-old) of diabetic Ins2+/C96Y mice (Akita mice) with HS (8% sodium chloride, 10-days) and analyzed endothelial function via wire myograph and cyclooxygenase (COX)-derived prostanoids pathway by ELISA, qPCR, and immunochemistry. At basal condition, DM_Exp mice did not manifest any vascular dysfunction, remodeling, or inflammation. However, HS increased the aortic contractility to phenylephrine and induced endothelial dysfunction (analyzed by acetylcholine-induced endothelium-dependent relaxation), vascular hydrogen peroxide production, COX2 expression, and prostaglandin E2 (PGE2) overproduction. Interestingly, ex vivo antioxidant treatment (tempol, 100µM) or COX1/2 (indomethacin, 10µM) or COX2 (NS398, 10µM) inhibitors improved or reverted the endothelial dysfunction in DM_Exp treated with HS. Finally, DM_Exp mice treated with HS exhibited greater circulating cytokines and chemokines accompanied by vascular inflammation. In summary, our findings indicate that prenatal exposure to maternal diabetes ...
Source: Am J Physiol Endocri... - Category: Endocrinology Authors: Source Type: research