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

Abstract

SUMMARY 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 IS 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 dairy Na balance was not significantly changed. Dairy 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. 1 " 7 The importance of these neuroendocrine changes remains largely uncertain, however, since reported plasma hormone levels generally have been less than those required to produce hypertension experimentally.

Enhanced resistance to permeability transition in interfibrillar cardiac mitochondria in dogs: effects of aging and long-term aldosterone infusion

“…We wished to avoid the confounding effects of thoracic or renal surgery required for aortic constriction, nephrectomy, or the Page renal wrap procedure (13,14,32); thus we used a controlled intravenous infusion of aldosterone via a pump implanted in the neck. Previous studies showed that aldosterone at 12 to 15 g·kg Ϫ1 ·day Ϫ1 increased mean arterial pressure by ϳ15 mmHg for up to 10 days in young mongrel dogs (5,10,27). We aimed to increase mean pressure by 15 to 20 mmHg, and in dose escalating pilot studies in our model system, we found that this required ϳ30 g·kg Ϫ1 ·day Ϫ1 .…”

“…Here we show that mitochondrial yield and functional differences between SSM and IFM were qualitatively similar in the LV and RV with responses to aging and aldosterone infusion (Figs. [3][4][5][6][7][8]. The present investigation was not designed to statistically compare the RV with the LV, as this would require a three-way ANOVA (chamber ϫ mitochondrial population ϫ age/treatment group) and thus a much larger sampled size to achieve acceptable statistical power.…”