VASCULAR RESPONSES IN TRANSGENIC HYPERTENSIVE MICE

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It has been know for many years that the renin-angiotensin system contributes importantly to some forms of hypertension. Some studies suggest that angiotensin II may be an important stimulus for generation of reactive oxygen species in blood vessels. Although hypertension is known to be associated with vascular dysfunction, little is known regrading cellular and molecular mechanisms that are associated with these changes. The studies outlined in this proposal will use two novel murine models of hypertension (systemic model, R+/A+ and renal-specific model, R+/KA+). The Specific Aims that will be examined are l) to examine the hypothesis that vascular dysfunction is present in the systemic model and renal- specific model. It is anticipated that the level of dysfunction will be greater in the systemic model as compared to the renal- specific model even though arterial pressure is similar in the two strains. 2) To examine the hypothesis that superoxide levels are enhanced within the vascular wall in the two models of hypertension. It is anticipated that levels of superoxide, which can inactivate NO, will be greater in the systemic model.