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Dissertation Defence - Loc Vinh Thang
(Conferences / Seminars / Lectures)
MACROPHAGE (MΦ)-DERIVED SUPEROXIDE DISRUPTS
SYMPATHETIC NERVE FUNCTION IN DEOXYCORTICOSTERONE
ACETATE (DOCA)-SALT HYPERTENSIVE RATS
HOST: JIM GALLIGAN
More than 65 million Americans have hypertension, which is a major risk for stroke, heart and kidney disease. Hypertension is a multi-organ disease that involves changes in nervous and immune system function. Sympathetic nerve activity is elevated in some hypertensive humans and in some animal models of hypertension, including the Deoxycorticosterone acetate-salt (DOCA-salt) model. DOCA-salt hypertension in rats is associated with the impairment of a α2-adrenergic autoreceptor (α2R), and increased level of superoxide (O2-) and macrophage (M) number in the mesenteric arterial (MA) adventitia. However, the relationship between M infiltration, O2- production and α2R impairment are unknown. This dissertation tested the hypothesis that as blood pressure increases in DOCA-salt rats, M infiltrate into the adventitia of MA. M release O2- that disrupts α2R function causing increased NE release and further increases in blood pressure. Time-course study was used to determine the temporal relationship between impaired function of sympathetic nerve terminal α2R and adventitial infiltration of pro-inflammatory M in MA from DOCA-salt hypertensive rats. Liposomal-encapsulated clodronate (LEC) was used to deplete adventitial M. The results of these studies revealed that pro-inflammatory M infiltration and increased O2- level in MA of DOCA-salt rats occurred after 10 days of initial blood pressure increase, but α2R impairment did not occur until a week after the infiltration of M. Furthermore, LEC prevented the development of the later phases of DOCA-salt hypertension by blocked the infiltration of M into the MA adventitia, reduced O2- level in the MA, and restored the α2R function. The novel aspect of this study is that it tested the hypothesis that M-derived O2- disrupts α2R function, which further contributes to the increase in blood pressure in DOCA-salt rats. Hypertension is a major public health concern. Therefore, clarifying the mechanism that leads to enhanced neurogenic vasoconstriction is important for new discoveries relevant to anti-hypertensive drug development. Furthermore, it is possible that vascular M markers could be used in the future to identify patients at risk for long-term changes in sympathetic nerve function at the first diagnosis of high blood pressure.
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884-3553
