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Genetic Background Influences Arterial Vasomotor Function in Male and Female Mice
Abstract
Cardiovascular disease (CVD) is the leading cause of death worldwide and is typically preceded by atherosclerotic lesion buildup within the arteries. Endothelial dysfunction is a known precursor to the development of atherosclerosis and subsequent progression of heart disease. While diet and environmental factors contribute to the progression of vascular diseases, there also exists a strong genetic component. To study the implication of genetic background on vasomotor and endothelial function, inbred mouse strains with varying degrees of endothelial impairment are often utilized. Previous research by our laboratory and others has reported variation in vasoconstrictor and vasodilator responses across male strains of mice in the thoracic aorta (TA). However, functional data from female populations and in other arteries that are implicated in atherosclerosis have not been elucidated. Also, it is unclear if vasomotor functional differences between sexes and strains are due to nitric oxide (NO)-mediated mechanisms.
The primary purposes of this dissertation research were to: 1) Assess vascular function along the large arterial network in male and female mice with distinct genetic backgrounds. 2) Determine the vasodilatory reliance these strains and arteries have on NO-mediated pathways.
Vasoreactivity to the endothelium-dependent vasodilator ACh varied across strains and throughout the arteries tested with some strains exhibiting artery-specific impairment. Vasoreactivity to the endothelium-independent vasodilator SNP was uniform across all strains and arteries tested other than the maximal dilation (%) in male carotid arteries (CA). Maximal constrictor responses (%) to the α1 adrenergic agonist phenylephrine (PE) varied across strains and arteries while sensitivity (EC50) did not. Results indicated some concentration-response heterogeneity in the female populations in relation to their male counterparts. Lastly, the most athero-prone strain (B6) relied most heavily upon NO-mediated vasorelaxation, while the least athero-prone strains (NZW, SJL) relied less upon NO for vasorelaxation.
Subject
Nitric Oxide (Synthase)Guanylate Cyclase
Cyclic Guanosine Monophosphate
Acetylcholine
Sodium Nitroprusside
Phenylephrine
Norepinephrine
Potassium Chloride
N-Nitro-L-arginine methyl ester hydrochloride
Gene Knockout
Thoracic Aorta
Abdominal Aorta
Carotid Artery, Femoral Artery
Reactive Oxygen Species
Super Oxide Dismutase
Tetrahydrobiopterin
Vascular Smooth Muscle Cells
Adrenergic Receptor
Estrogen Receptor
Cyclooxygenase
Endothelial Derived Hyperpolarizing Factor
Hydrogen Peroxide
Epoxyeicosatrienoic Acid
Prostaglandin
Prostacyclin
Vascular Endothelial Growth Factor
Coronary Artery Disease
Cardiovascular Disease
American Heart Association
Citation
Holly, Dylan Stone (2022). Genetic Background Influences Arterial Vasomotor Function in Male and Female Mice. Doctoral dissertation, Texas A&M University. Available electronically from https : / /hdl .handle .net /1969 .1 /197970.