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Genetic Background Influences Endothelium‐dependent Vasomotor Function in Large Arteries
Author(s) -
Holly Dylan,
Kim Hyosean,
Gaytan Samantha,
Woodman Christopher,
Massett Michael
Publication year - 2021
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.2021.35.s1.02058
Subject(s) - myograph , vasomotor , endothelium , sodium nitroprusside , vasodilation , nitric oxide , medicine , endothelial dysfunction , aorta , cardiology , endocrinology
Endothelial dysfunction is associated with a host of disease states including cardiovascular disease, diabetes, chronic kidney disease, and atherosclerosis. Previous research by our laboratory has shown that vasomotor function, and more specifically endothelium‐dependent vasorelaxation responses, differ across large arteries from mice with distinct genetic backgrounds. However, it is unclear how much of the observed variation in endothelium‐dependent vasorelaxation is due to nitric oxide (NO) mediated pathways. Objective The purpose of this study was to test the hypothesis that strain‐dependent vasorelaxation differences were primarily the result of differences in reliance on NO‐mediated pathways. Methods Vasomotor function was assessed in thoracic aorta, abdominal aorta, carotid arteries, and femoral arteries from four inbred strains (SJL/J (SJL), DBA/2J (DBA), NZW/LacJ (NZW) and C57BL/6J (B6)) of mice. Strains were chosen based on previously documented vasomotor variation and susceptibility to clinically significant pathologies. Arteries were dissected, cut into 2mm segments, and mounted in a wire myograph system. Arterial segments were stretched to a resting tension equivalent to a pressure of 90mmHg for all strains based on a passive stretch and relaxation tension‐force assessment. Increasing concentrations of the endothelium‐dependent vasodilator acetylcholine (ACh, 1x10 ‐9 – 1x10 ‐5 M) and endothelium‐independent vasodilator sodium nitroprusside (SNP, 1x10 ‐9 – 1x10 ‐5 M) were used to assess vasorelaxation responses. To assess reliance on NO, vasorelaxation responses to Ach and SNP were assessed in the presence of a nitric oxide synthase inhibitor (NOS). One arterial segment from each group was treated with the NOS inhibitor N omega‐Nitro‐L‐arginine methyl ester hydrochloride (L‐NAME: 10x4 M) for thirty minutes. Results Two way ANOVA revealed a significant main effect of strain in vasorelaxation responses to ACh for all arteries tested (P <.0001) and no significant differences in response to SNP. Maximal relaxation responses to ACh were significantly inhibited in all arterial segments treated with L‐NAME, while no differences were detected for L‐NAME treated vessels in response to SNP. These findings indicate that large arteries have a strong dependence on NO‐mediated, endothelium‐dependent pathways to maintain vascular regulation. Furthermore, strain‐dependent vasorelaxation differences were abolished in the presence of L‐NAME indicating that strain differences were NO‐dependent. Conclusion These findings indicate a strong influence of genetic background on endothelial function and suggest that these differences are primarily due to strain related reliance on NO for endothelium‐dependent vasodilation.