The pathophysiologic hallmark of essential hypertension is an elevated peripheral vascular resistance. The mechanism of this resistance abnormality remains an enigma. Previous research has indicated that structural vascular abnormalities, increased alpha-receptor sensitivity and abnormalities in membrane transport of cations may explain the increased arterial resistances in patients with hypertension. Other research has indicated that these same factors participate in salt-sensitive hypertension. The ultimate objectives of this proposal, based on three related studies of the human forearm vasculature, are to 1) define the cause(s) in the hypertensive patient for an increased arterial reactivity to vasopressor agents, especially norepinephrine (NE), 2) identify the pathophysiologic mechanism conferring """"""""salt-sensitivity"""""""" present in some hypertensive patients, 3) determine if the abnormalities found are specific for vascular tissue or present in the pupillary responses of the eye as well. Three criteria for evaluating vascular structure, one criterion of sympathetic forearm vascular tone, and one measure each of alpha-receptor sensitivity and affinity will be obtained by constructing complete dose of intraarterial NE to calculated forearm vascular resistance response in hypertensive and normotensive humans. Vascular structure will also be evaluated by minimum FAVR after 10' of ischemic forearm exercise, and the similarity of vascular reactivity to NE and angiotensin II. Forearm sympathetic tone will be evaluated by two methods: 1) vasodilator response to i.a. phentolamine and 2) the product of sympathetic drive (plasma catecholamines) and forearm alpha-receptor sensitivity (l/dose of i.a. NE which increases FAVR by 50%). Membrane transport of cations will be evaluated by in vitro assay of erythrocyte Na+/K+ fluxes. The mechanism of salt-sensitivity in hypertension will be investigated by performing the previous studies on hypertensive and normotensive subjects during both high-salt (250 mEq/d) and low-salt (20 mEq/d) balance. The presence of abnormal reactivity in nonvascular tissue will be investigated by pupillometric assessment of the light reflex, pupil size in the dark and mydriatic sensitivity to phenylephrine.
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