Mouse Genetic Background influences Endothelial Function along the Mouse Vascular Tree

Abstract

The endothelium is critical for maintaining vascular integrity and protecting against cardiovascular disease. Endothelial dysfunction is associated with a host of disease states including cardiovascular disease, diabetes, chronic kidney disease, and Alzheimer's disease. However, it is unclear whether endothelial function or dysfunction varies throughout the vasculature. In addition, accumulating evidence suggests that endothelial function, and more generally vasomotor function, is genetically regulated. The purpose of this study was to determine the influence of genetic background on vasomotor function in blood vessels of differing size. Vasomotor function was measured in aorta (thoracic (TA), and abdominal (AA)) and conduit arteries (carotid artery (CA) and femoral artery (FA)) from two inbred strains (NZW/LacJ (NZW) and C57BL/6J (B6)) of mice. Arteries were dissected, cut into 2 mm segments, and mounted in a wire myograph system. Increasing concentrations of phenylephrine (PE, 1×10−9 – 1×10−5M) were used to measure contractile responses, while increasing concentrations of the endothelium‐dependent vasodilator acetylcholine (ACh, 1×10−9 – 1×10−5M) and endothelium‐independent vasodilator sodium nitroprusside (SNP, 1×10−9 – 1×10−5M) were used to assess relaxation responses. Contractile responses to PE were not significantly different between strains across all vessels. Endothelium‐dependent relaxation to ACh was significantly impaired in TA (P = .0001), AA (P = .0019), and FA (P = .0002) from NZW as compared to B6, while CA relaxation responses were not statistically different between groups. Sensitivity to ACh as determined by IC50 was impaired in NZW TA (P = .0006), AA (P = .0005), CA (P = .001), and FA (P = .0003). Relaxation responses to the endothelium‐independent vasodilator SNP were not statistically different in the AA, CA and FA, while TA relaxation to SNP was statistically lower in B6 TA compared to NZW (P = .02). Sensitivity to SNP was not statistically different between groups for TA, CA, and FA but NZW AA showed a greater sensitivity to SNP than did B6 (P = .0304). These findings indicate a strong influence of genetic background on vasomotor function and could be important in understanding the implications that genetics have on vascular response to vasoactive agents.Support or Funding InformationThis work was supported by a Texas A&M Triads for Transformation grant (Michael Massett, Christopher Woodman), a Texas A&M Merit Fellowship (Dylan Holly), and a Texas A&M College of Education Strategic Research Award (Song Yi Shin).This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.