Abstract 402: Effect of Aging on Endothelial Function in a Genetic Mouse Model of Hypertension

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Although previous studies have demonstrated that there is a strong genetic component associated with the development of hypertension, angiotensin II-infusion represents the most commonly used model of hypertension, especially in mice. While the BPH/2 mouse represents a genetic, non-angiotensin II-dependent, model of hypertension, there is limited information regarding endothelial responses and, to our knowledge, no information regarding the effect of aging on blood pressure or endothelial function in this model. The goal of this study was to test the hypothesis that endothelial dysfunction is present in the carotid artery in the genetically hypertensive BPH/2 mouse and that the degree of endothelial dysfunction in this model worsens with age. Systolic blood pressure (SBP) and vascular function was examined in young (5 months) and aged (12 months of age) BPN/3 and BPH/2 mice. SBP was significantly greater (P<0.05) in young hypertensive mice as compared to their normotensive counterparts (e.g., SBP was 151±6 and 122±3 mmHg in BPH/2 and BPN/3 mice, respectively). Blood pressure was not affected by age as SBP averaged 147±3 and 127±3 mmHg in aged BPH/2 and BPN/3 mice, respectively. Acetylcholine-induced relaxation was impaired by approximately 30% (P<0.05) in BPH/2 mice as compared to BPN/3 mice (e.g., 10 μM acetylcholine produced 65±6 and 90±5% relaxation in BPH/2 and BPN/3 mice, respectively). Moreover, the degree of endothelial dysfunction was markedly greater (P<0.05) in aged as compared to young BPH/2 mice. Tempol, a scavenger of superoxide, was very effective in improving endothelial responses in both young and aged BPH/2 mice, suggesting an important role for superoxide in the impairment of endothelial function. Impairment of acetylcholine-induced relaxation was selective for endothelium as responses to nitroprusside were not altered in BPH/2 mice and unaffected by age. These data demonstrate that endothelial dysfunction is present in the carotid artery of BPH/2 mice and is mediated in large part by superoxide. Aging appears to be associated with the worsening of the vascular phenotype and as such BPH/2 mice represent a novel genetic mouse model of hypertension-related, aging-induced endothelial dysfunction. NIH HL089884 & HL107632

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