Diabetes-related sex differences in the brain endothelin system following ischemia in vivo and in human brain endothelial cells in vitro.

Diabetes-related sex differences in the brain endothelin system following ischemia in vivo and in human brain endothelial cells in vitro. Can J Physiol Pharmacol. 2020 Jun 04;: Authors: Abdul Y, Li W, Vargas JD, Grant E, He L, Jamil S, Ergul A Abstract The endothelin (ET) system has been implicated to contribute to the pathophysiology of cognitive impairment and stroke in experimental diabetes. Our goals were to test the hypotheses that 1) circulating and/or peri-infarct ET-1 levels are elevated after stroke in both sexes and this increase is greater in diabetes, 2) ET receptors are differentially regulated in the diabetic brain, 3) brain microvascular endothelial cells (BMVEC) of female and male origin express the ETA receptor subtype, and 4) diabetes and stroke-mimicking conditions increase ET-1 levels in BMVECs of both sexes. Control and diabetic rats were randomized to sham or stroke surgery. BMVECs of male (hBEC5i) and female (hCMEC/D3) origin, cultured under normal and diabetes-mimicking conditions, were exposed to normoxia or hypoxia. Circulating ET-1 levels were higher in diabetic animals and this was more pronounced in the male cohort. Stroke did not further increase plasma ET-1. Tissue ET-1 levels were increased after stroke in males, whereas peri-infarct ET-1 increased in both control and diabetic females. Male BMVECs secreted more ET-1. Hypoxia increased ET-1 in both cell types. There are sex differences in the stroke and...
Source: Canadian Journal of Physiology and Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Can J Physiol Pharmacol Source Type: research