Are hypertensive effects of aldosterone, angiotensin, vasopressin, and norepinephrine chronically additive?

The effects of chronic combined administration of angiotensin II, norepinephrine, aldosterone, and arginine vasopressin were compared with the response to each of these hormones administered alone. The studies were performed in dogs to determine the extent to which moderately inappropriate elevations of these hormones could enhance each other's ability to produce chronic hypertension and influence Na and water homeostasis. Blood pressure sensitivity to Na intake was also evaluated by infusing the hormones for 11 days at normal levels of Na intake followed by 11 days at high Na intake with ad libitum drinking. Combined hormone administration did not enhance each hormone's singular hypertensive actions. With aldosterone infusion alone and normal Na intake, mean arterial pressure rose nearly 15 mm Hg and an additional 3 mm Hg during high Na intake. Combined hormone infusion also resulted in a nearly 15 mm Hg rise during normal Na intake and an additional 3 mm Hg rise in mean arterial pressure during high Na intake. Marked Na retention and hypernatremia were observed with aldosterone infusion, while hyponatremia characterized arginine vasopressin infusion. The combined hormone infusion resulted in a tendency toward hypernatremia, although daily Na balance was not significantly changed. Daily water turnover was substantially increased and urine osmolality fell to hypoosmotic levels, despite elevated arginine vasopressin levels. Even with high Na intake, dogs receiving either angiotensin II, arginine vasopressin, or norepinephrine at the same concentrations showed 4 to 10 mm Hg increases in mean arterial pressure. Thus, humoral summation or synergism of these hormones probably does not play a major role in the development of chronic hypertension.