SUMMARY We studied the combined effect of subpressor amounts of angiotensin and long-term sodium chloride infusion on arterial pressure in 16 dogs for periods of 2-8 weeks. In dogs receiving 3.5 liters of isotonic NaCl daily, but no angiotensin, the arterial pressure increased an average of only 3 mm Hg. When angiotensin was infused continuously at a rate of 5 ng/kg per min (a rate too small to cause an observable immediate increase in pressure), subsequent infusion of 3.5 liters of saline daily then increased the pressure by 39 mm Hg. The urinary output of sodium increased to the same extent in both instances, that is, there was no extra sodium loss because of the elevated pressure. This suggests that the angiotensin significantly blocked the normal "pressure natriuresis" usually seen with such large increases in pressure. However, the plasma aldosterone levels during angiotensin infusion were not found to be different from those in the absence of angiotensin. Therefore, we have suggested that the tendency of the kidneys to retain sodium under the influence of angiotensin was probably caused mainly by a direct effect of angiotensin on the kidney itself. Such a direct renal sodium-retaining effect also could be a contributing factor in the marked hypertension that results from salt administration in the presence of small amounts of angiotensin.
We studied the role of the sino-aortic baroreceptors in the gradual development of hypertension induced by prolonged administration of small amounts of angiotensin II (A II) in intact dogs and dogs with denervated sino-aortic baroreceptors. Short-term 1-hour infusions of A II(1.0-100 ng/kg per min) showed that conscious denervated dogs had twice the pressor sensitivity of intact dogs. Long-term infusions of A II at 5.0 ng/kg per min (2-3 weeks) with continuous 24-hour recordings of arterial pressure showed that intact dogs required 28 hours to reach the same level of pressure attained by denervated dogs during the 1st hour of infusion. At the 28th hour the pressure in both groups was 70% of the maximum value attained by the 7th day of infusion. Both intact and denervated dogs reached nearly the same plateau level of pressure, the magnitude being directly related both the the A II infusion rate and the daily sodium intake. Cardiac output in intact dogs initially decreased after the onset of A II infusion, but by the 5th day of infusion it was 38% above control, whereas blood volume was unchanged. Heart rate returned to normal after a reduction during the 1st day of infusion in intact dogs. Plasma renin activity could not be detected after 24 hours of A II infusion in either intact or denervated dogs. The data indicate that about 35% of the hypertensive effect of A II results from its acute pressor action, and an additional 35% of the gradual increase in arterial pressure is in large measure a result of baroreceptor resetting. We conclude that the final 30% increase in pressure seems to result from increased cardiac output, the cause of which may be decreased vascular compliance. since the blood volume remains unaltered.
The steady-state relationship between mean arterial pressure (AP) and output of sodium and water was determined for one-kidney control (1KC), one-kidney Goldblatt (1KG), normotensive Wistar-Kyoto (WKY), and Okamoto spontaneously hypertensive rats (SHR). Control fluid intake (given by intravenous infusion) was set at approximately 30 ml/day Ringer solution. The infusion rate was then increased progressively to 2, 4, and 8 times control for 24- to 48-h periods each. Control AP averaged 115 Torr in 1KC, 152 Torr in 1KG, 120 Torr in WKY, and 158 Torr in SHR. The eightfold increase in salt and water intake was accompanied by almost equal increase in salt and water output and increases in AP to 157 Torr in 1KC, 190 Torr in 1KG, 126 Torr in WKY, and 166 Torr in SHR. The arterial pressure-urinary output relationship in 1KG is parallel to that of 1KC but shifted to higher AP levels. Similarly, this relationship in SHR is parallel to that of WKY but shifted to higher AP levels. This parallel shift is indicative of uniform renal vasoconstriction but normal functional renal mass in the SHR.
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.
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