Hypertension (HT) affects one-third of the adult population of the United States, and is a major risk factor for subsequent development of cardiovascular disease. Increased sympathetic outflow precedes the development of HT in humans and is associated with the development of HT in deoxycorticosterone acetate (DOCA)-salt rats. The celiac, along with the superior (SMG) and inferior mesenteric ganglia (IMG) contain the cell bodies of postganglionic sympathetic neurons that innervate the abdomino-pelvic organs and blood vessels. The highly compliant veins of the abdomino-pelvic region represent the largest readily available reserve of blood in the body. It is from these vessels, in response to sympathetic nervous system-mediated venoconstriction, that blood is mobilized during acute sympathetic activation (e.g., during hemorrhage or exercise). It is likely that a chronic increase in the outflow of efferent sympathetic signals from these ganglia contribute to the rise in arterial pressure in HT through increased venoconstriction and the subsequent reduction in capacitance in this region. The overall objective of the studies described in this dissertation was to uncover the changes in cellular and synaptic function that are taking place in DOCA-salt hypertension. I began by using the rat IMG as a model of synaptic transmission to test the hypothesis that the safety factor (i.e., the tendency for a preganglionic action potential to evoke an action potential in a postganglionic neuron) is increased in DOCA-salt HT. Intracellular recordings of IMG neurons with concurrent stimulation of the preganglionic nerve bundle revealed that in HT, a greater number of neurons receive strong synaptic inputs. Application of high-frequency, low amplitude stimulation of the preganglionic nerve revealed that a greater proportion of neurons from NT rats underwent long-term potentiation of excitatory postsynaptic potential (EPSP) amplitude beyond action potential threshold. In a separate series of experiments, I used pseudorabies-virus retrograde tracing to identify vein- and artery-projecting neurons of the SMG. The properties of these identified neurons were compared between NT and DOCA-salt HT rats using intracellular recording techniques. I found that the amplitude of the depolarization induced by exogenous nicotine is reduced in both vein- and artery-projecting neurons from HT but not NT rats. Application of exogenous glucocorticoid (hydrocortisone 21-hemisuccinate) (CORT) revealed that vein-projecting neurons from HT rats were hyperpolarized to a significantly lower degree than artery neurons from NT and HT rats, as well as vein-projecting neurons from NT rats. The direct hyperpolarizing effect of CORT was blocked by the glucocorticoid receptor antagonist, RU 486. These results suggest that fast synaptic transmission and cellular properties of prevertebral sympathetic ganglion neurons are altered in DOCA-salt HT.
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