The pathogenesis and management of neurogenic orthostatic hypotension and the postural tachycardia syndrome (POTS) are poorly understood. Recent studies suggest that POTS is heterogenous and that a number of mechanisms might be operative. These include gender-specificity of orthostatic intolerance, a restricted autonomic neuropathy, hypovolemia, venous pooling, alpha- and beta-receptor abnormalities and alterations in brainstem mechanisms, including perturbed central baroreflex regulation. We will undertake a detailed comparative study of POTS with the well- defined progressive autonomic disorders (multiple system atrophy [MSA}, pure autonomic failure (PAF} and the autonomic neuropathies). The research studies will consist of comprehensive clinical and laboratory autonomic studies using questionnaires, non-invasive techniques of Finapres and impedance plethysmography, infusions of vasoactive agents to evaluate alpha- and beta-receptor sensitivity and baroreflex again, and power spectral analysis, designed in such a way to better define the underlying mechanisms of orthostatic intolerance. We have accumulated a large cohort of patients with POTS and will be able to define its natural history. Insights gained from these studies will be used to improve the management of POTS, including the acute laboratory administration of agents that can provide mechanistic insights and have therapeutic potential. The efficacy of physical countermaneuvers to improve orthostatic tolerance in POTS will be evaluated. We will determine whether the orthostatic intolerance of normal women and those with POTS are dependent on the phase of the menstrual cycle and will attempt to determine whether central regulation of autonomic function is impaired in POTS.
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