Contributions of endothelin-1 and l-arginine to blunted cutaneous microvascular function in young, black women

• Published in: American journal of physiology. Heart and circulatory physiology Vol. 322; no. 2; pp. H260 - H268
• Main Authors: Akins, John D, Richey, Rauchelle E, Campbell, Jeremiah C, Martin, Zachary T, Olvera, Guillermo, Brothers, R Matthew
• Format: Journal Article
• Language: English
• Published: United States American Physiological Society 01.02.2022
• Series: New Developments in Translational Microcirculatory Research
• Subjects: Arginine; Arginine - metabolism; Bioavailability; Black or African American; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - ethnology; Dilation; Endothelin 1; Endothelin Receptor Antagonists - pharmacology; Endothelins - metabolism; Female; Heart diseases; Heating; Hispanic people; Humans; Microdialysis; Microvasculature; Microvessels - drug effects; Microvessels - metabolism; Microvessels - physiology; Minority & ethnic groups; Nitric oxide; Nitric Oxide - metabolism; Peptides, Cyclic - pharmacology; Receptors; Receptors, Endothelin - metabolism; Sodium nitroprusside; Vasodilation; Women; Young Adult; cardiovascular disease; vascular function; endothelin-1; l-arginine; non-Hispanic black women
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00457.2021

Non-Hispanic black (BL) individuals have the greatest prevalence of cardiovascular disease (CVD), relative to other racial/ethnic groups (e.g., non-Hispanic white population; WH), which may be secondary to blunted vascular function. Although women typically present with reduced CVD relative to men of the same racial/ethnic group, the prevalence is similar between BL women and men though the mechanisms differ. This study hypothesized that reduced microvascular function in young, BL women is associated with endothelin-1 (ET-1) overactivity or insufficient l-arginine bioavailability. Nine BL and nine WH women participated (age: 20 ± 2 vs. 22 ± 2 yr). Cutaneous microvascular function was assessed during 39°C local heating, whereas lactated Ringer's (control), BQ-123 (ET-1 receptor type A antagonist), BQ-788 (ET-1 receptor type B antagonist), or l-arginine were infused via intradermal microdialysis to modify cutaneous vascular conductance (CVC). Subsequent infusion of -nitro-l-arginine methyl ester allowed for quantification of the nitric oxide (NO) contribution to vasodilation, whereas combined sodium nitroprusside and 43°C heating allowed for normalization to maximal CVC (%CVC ). BL women had blunted %CVC and NO contribution to dilation during the 39°C plateau ( < 0.027 for both). BQ-123 improved this response through augmented NO-mediated dilation ( < 0.048 for both). BQ-788 and l-arginine did not alter the CVC responses ( > 0.835 for both) or the NO contribution ( > 0.371 for both). Cutaneous microvascular function is reduced in BL women, and ET-1 receptor type A may contribute to this reduced function. Further research is needed to better characterize these mechanisms in young, BL women. Cardiovascular disease remains a burden in the United States non-Hispanic black (BL) population, although its manifestation through blunted vasodilation in this population is different between men and women. Accordingly, this study determined that reduced microvascular function in young, BL women may be partially controlled by endothelin-1 (ET-1) type A receptors, although neither type B receptors nor insufficient l-arginine bioavailability seems to contribute to this response. Accordingly, further research is needed to better characterize these ET-1 related mechanisms and illuminate other pathways that may contribute to this disparate vascular function in young, BL women.