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Genetic Background influences Endothelial Function along the Mouse Vascular Tree
Author(s) -
Holly Dylan Stone,
Massett Michael,
Gaytan Samantha,
Kim Hyoseon,
Shin Songyi,
Woodman Christopher
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2020.34.s1.05781
Subject(s) - myograph , medicine , sodium nitroprusside , endothelial dysfunction , vasodilation , vasoconstriction , phenylephrine , vasomotor , endothelium , endocrinology , cardiology , nitric oxide , blood pressure
The endothelium is crucial for its role in 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 atherosclerosis. 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 performance was measured in aorta (thoracic (TA), and abdominal (AA)) and conduit arteries (carotid artery (CA) and femoral artery (FA)) from four inbred strains (SJL/J (SJL), DBA/2J (DBA), 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 −5 M) were used to measure contractile responses, while increasing concentrations of the endothelium‐dependent vasodilator acetylcholine (ACh, 1×10 −9 – 1×10 −5 M) and endothelium‐independent vasodilator sodium nitroprusside (SNP, 1×10 −9 – 1×10 −5 M) were used to assess relaxation responses. Two way ANOVA revealed a significant main effect of strain in response to PE for AA (P = .0032) and CA (P = .0098). Post hoc analysis for max contractile response showed impaired vasoconstriction in NZW AA compared to B6 (P = .0004). In response to ACh, a significant main effect of strain was found for all vessels (TA: P = <.0001, AA: P = .0156, CA: P = .0069, FA: P = <.0001). Post hoc analysis showed that TA max vasorelaxation was impaired for all strains (NZW: P = < .0001, DBA: P = .0140, SJL: P = < .0001) and that NZW FA were impaired when compared to B6 ( P = .0015). A significant main effect of strain in response to SNP was found in TA (P = .0011), AA (P = .0086), and CA (P = < .0001). Relaxation responses to SNP were not significantly different between strains. These findings indicate a strong influence of genetic background on endothelial function and could be important in understanding the implications that genetics have on vascular response to vasoactive agents. Support or Funding Information This work was supported by a Texas A&M Triads for Transformation grant (MPM), a Texas A&M Merit Fellowship (DH), a Texas A&M College of Education Strategic Research Award (SYS), and J.L. Huffines Institute of Sports Medicine and Human Performance (SYS).