Sodium, extracellular fluid volume, and cardiac output changes in the genesis of mineralocorticoid hypertension in the intact dog.

Twenty-four trained, conscious dogs with chronically implanted iliac catheters were used to assess the relative roles of sodium (Na) and volume in the development of mineralocorticoid hypertension. All were maintained on restricted Na diets; supplemental Na was given as slow I.V. infusions of 0.9% NaCl solution. The effect of gradual replenishment of total body sodium on arterial blood pressure (BP), cardiac output (CO), total peripheral resistance (TPR) and extracellular fluid volume (ECFV) was assessed at four separate levels of cumulative Na intake (70,140,420 and 840 mEq). The sequence of changes in 12 metyrapone-treated dogs was compared with 12 untreated controls submitted to the same protocol. Changes in fluid volumes and CO were virtually identical in the two groups; however, only dogs previously treated with metyrapone became significantly hypertensive (AMAP » 16 and 28 mm Hg,p < 0.001). Within the metyrapone-treated groups, increases in volume and flow led to markedly different TPR responses dependent on level of cumulative sodium Intake; at levels ^ 140 TPR was lowered as output increased, but as levels > 140 TPR and BP rose in the face of increases in output and ECFV that were not greater than those found at 140 mEq cumulative Na intake. These findings suggest that this steroid-induced hypertension in the dog is "resistance-mediated" from its earliest stages, and that restoration of sodium stores rather than volume expansion played the more important role in the initiation of this hypertension. (Hypertension 1: 331-336, 1979)