Volume and cardiac factors in the genesis of mineralocorticoid hypertension in the conscious dog

Abstract

Steroid induced hypertension is well known to be salt and water dependent. In both the clinical and experimental forms of this disorder, salt loading increases while salt deprivation decreases arterial blood pressure [1, 2]. We have previously reported our experience in conscious dogs [3] in which we performed serial quantitative assessment of hemodynamic and volume alterations during sodium deprivation and during gradual replenishment of total body sodium; the aim of the study was to dissociate between the role of sodium and the role of changes of blood and extracellular fluid volumes in the genesis of steroid induced hypertension. The sequence of changes in metyrapone treated dogs (100 mg/kg/day) was compared with untreated controls submitted to the same protocol. Restoration of sodium stores failed to alter arterial blood pressure in untreated dogs while, in contrast, it led to significant hypertension in metyrapone treated dogs. Changes in cardiac output and fluid volumes were virtually identical at every stage in the normotensive and hypertensive dogs. These findings suggested that changes in flow, which occurred in all dogs following salt and water administration, were not responsible for the subsequent rise in arterial pressure. The increased arterial pressure in metyrapone treated dogs was clearly due to a rise in total peripheral resistance when these dogs attained a critical amount of cumulative sodium intake. In fact, these studies have followed a quantitative evaluation of the relationship between sodium intake and total peripheral resistance changes in the presence of excess electrolyte active steroids; increases in cardiac output by as much as 20% were not associated with increased total peripheral resistance or blood pressure when cumulative sodium intake was limited to 140 mEq.