Failure of chronic aldosterone infusion to increase arterial pressure in dogs with angiotensin-induced hypertension.

TE Lohmeier, AW Cowley Jr, JW DeClue… - Circulation …, 1978 - Am Heart Assoc
TE Lohmeier, AW Cowley Jr, JW DeClue, AC Guyton
Circulation Research, 1978Am Heart Assoc
To generate quantitative data relating to the hypertensive activity of aldosterone, 9/xg/kg per
day (4 times normal) aldosterone (4-ALDO) were infused chronically in both
adrenalectomized and intact dogs until steady state conditions were achieved. Mean arterial
pressure (MAP) was monitored continuously, 24 hours per day, and daily steady state
values for MAP based on approximately 600 sample points per day were determined by
employing computerized data analysis. In some studies, angiotensin II (A II) was also …
Summary
To generate quantitative data relating to the hypertensive activity of aldosterone, 9/xg/kg per day (4 times normal) aldosterone (4-ALDO) were infused chronically in both adrenalectomized and intact dogs until steady state conditions were achieved. Mean arterial pressure (MAP) was monitored continuously, 24 hours per day, and daily steady state values for MAP based on approximately 600 sample points per day were determined by employing computerized data analysis. In some studies, angiotensin II (A II) was also infused chronically (5 ng/kg per min) prior to and during 4-ALDO administration to maintain plasma levels of A II constant. 4-ALDO infusion in intact dogs maintained on 75 mEq sodium per day increased MAP by only 13 mm Hg compared to a greater than 30 mm Hg rise observed with A II infusion alone, even though plasma aldosterone concentration rose in these experiments only two-thirds as much as when 4-ALDO was infused. When A II was infused chronically, a fall in plasma A II concentration could not compensate for the hypertensive effects of superimposed 4-ALDO infusion; therefore, maximal aldosterone-induced hypertension was expected. However, in both adrenalectomized and intact dogs, the further addition of 4-ALDO failed to increase the degree of A II-induced hypertension and failed to promote sodium retention. Chronic A II infusion in intact dogs maintained on 75 and 190 mEq sodium per day produced a sustained increase in plasma aldosterone concentration (2.7 and 1.6 times control, respectively) as well as kaliuresis and hypokalemia. Infusion of A II in adrenalectomized dogs produced hyperkalemia, not hypokalemia. The data indicate that high plasma levels of aldosterone, at least over a period of several weeks, have only weak hypertensive effects in the dog, particularly in instances in which the aldosteronism is associated with a primary increase in A II.
ALTHOUGH aldosterone is considered by many to have an important role in the genesis and maintenance of hypertension associated with increased activity of the renin-angiotensin-aldosterone system, in fact, there are few quantitative data to distinguish the suspected hypertensive effects of the aldosterone from that of simultaneously formed angiotensin. The best example of the blood pressure-elevating effect of aldosterone is the syndrome of primary aldosteronism. Patients with this syndrome have hyperaldosteronemia and mild-to-severe hypertension. 1" 4 However, in both human subjects and experimental animals, chronic infusions of aldosterone which produce strong mineralocorticoid effects have been reported to produce little or no increase in arterial pressure. 5" 8 This is in contrast to the aldosteronism and severe hypertension which accompany chronic angiotensin II (A II) infusion in experimental animals, or the aldosteronism and severe hypertension observed in patients with primary reninism. 9'l0 Some of the factors that must be considered as possible contributors to the reported variability in the long-term blood pressure response to aldosterone include:(1) the plasma level of al-
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