LAUSR

The endoplasmic reticulum is a multipurpose organelle found in most human cells, including endothelial and smooth muscle cells of blood vessels. It plays a key role in posttranslational folding of new proteins and reprocessing of misfolded or damaged proteins. Under certain conditions, the accumulation of unfolded proteins can trigger a quality control system (i.e., the unfolded protein response) that restores protein homeostasis in the endoplasmic reticulum. However, the unfolded protein response can simultaneously augment the formation of reactive oxygen species and inflammatory mediators which can induce vascular dysfunction. Despite our understanding of the relation between endoplasmic reticulum stress and vascular dysfunction in animal and human models, the sex-dependent influence of the endoplasmic reticulum on microvascular function has not been explored. Therefore, we tested the hypothesis that compared with placebo, acute ingestion of tauroursodeoxycholic acid (TUDCA) would improve microvascular function to the same extent in men and women. Twelve young healthy adults (6 women, 26 ± 5 yrs) were studied ~8 hours following ingestion of a placebo or 1,500 mg of TUDCA, a chemical chaperone that inhibits endoplasmic reticulum stress. Experiments were randomized, counterbalanced, and separated by at least 7 days. Venous plasma TUDCA and its taurine conjugated form, ursodeoxycholic acid, were measured for both conditions via high-performance liquid chromatography. Microvascular function was assessed using post-occlusive reactive hyperemia (Doppler ultrasound) and was normalized to mean arterial blood pressure. Compared with placebo (men, 13 ± 15 ng/ml; women, 6 ± 2 ng/ml), TUDCA ingestion increased plasma concentrations (men, 80 ± 43 ng/ml; women, 140 ± 93 ng/ml; P = 0.05). Similarly, compared with placebo (men, 13 ± 14 ng/ml; women, 7 ± 4 ng/ml), plasma ursodeoxycholic acid increased following TUDCA ingestion (men, 666 ± 237 ng/ml; women, 559± 458 ng/ml; P < 0.01). Plasma TUDCA and ursodeoxycholic acid concentrations did not vary between sexes (both P > 0.4). Peak vascular conductance did not differ between placebo and TUDCA conditions ( P = 0.7), an effect that did not vary between men and women (men: placebo, 4.1 ± 1.1 ml/min/mmHg vs. TUDCA, 4.1 ± 1.1 ml/min/mmHg; women: placebo, 3.2 ± 1.1 ml/min/mmHg vs. TUDCA, 3.0 ± 1.1 ml/min/mmHg; P = 0.6). Likewise, reactive hyperemia area under the curve did not differ between placebo and TUDCA conditions ( P = 0.5), nor did it vary by sex ( P = 0.2). Contrary to our hypothesis, these data suggest that acute ingestion of tauroursodeoxycholic acid does not alter microvascular function in young healthy men and women. UNTHSC Seed Grant This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.