Role of angiotensin II and potassium in the long-term regulation of aldosterone secretion in intact conscious dogs.

McCaa, R E; McCaa, Connie S.; Guyton, Arthur C.

doi:10.1161/01.res.36.6.57

Cited by 43 publications

(14 citation statements)

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“…fore surgery, extremely high aldosterone levels were maintained by angiotensin II despite the inhibitory effects of mild hypokalemia (3.3 mmol/liter in Patient HE, 3.1 mmol/liter in Patient MC). While there is still controversy concerning the effect of sustained increases in angiotensin II on aldosterone, 22 " 24 the present findings support those of the Glasgow group 25 who showed similar angiotensin/aldosterone relationships in a mixed group of patients with malignant hypertension, renin-secreting tumor, and renal artery stenosis. We conclude, first, that long-standing elevations in angiotensin II secondary to renal ischemia can sustain high circulating levels of aldosterone; and, second, that aldosterone responsiveness to endogenous angiotensin II stimulation is increased in established renovascular hypertension.…”

Section: -supporting

confidence: 82%

Mechanisms in human renovascular hypertension.

Maslowski¹,

Nicholls²,

Espiner³

et al. 1983

Hypertension

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SUMMARY To clarify the pathophysiology of renovascular hypertension, we monitored intraarterial pressure continuously and measured hourly hormone levels for 24 hours under carefully controlled conditions in two hypertensive patients with unilateral renal artery occlusion. Comparison of the results with those obtained when the patients were normotensive 3 months after uninephrectomy indicated that, while the renin-angiotensin system played a central role in maintaining the hypertension, the sympathetic nervous system also contributed and, in addition, modulated short-term arterial pressure fluctuations. In the untreated state, the sympathetic regulation of renin secretion was heightened, and angiotensin H/aldosterone dose-responsiveness was augmented. It is suggested that these adaptive changes might serve to offset the tendency to severe sodium depletion and thence exacerbation of the hypertension. (Hypertension 5: 597-602, 1983) KEY WORDS • renal hypertension • renin • angiotensin • aldosterone • catecholamines T HE mechanisms underlying renal hypertension are unclear despite intensive study. For the more common form in humans -unilateral renal artery stenosis with the contralateral kidney intact (the equivalent of two-kidney, one clip hypertension in experimental animals 1 ), the renin-angiotensin system is thought to play a central role both in the development and maintenance of hypertension.2 More contentious and less researched is involvement of the sympathetic nervous system in regulating arterial pressure and controlling renin release from the ischemic kidney. Much of our knowledge linking pressure and hormone changes is based on animal experiments, but prominent species differences 3 ' 4 hamper application of these findings to humans. Previous studies in humans have tended to focus on a single pathophysiological variable -usually renin -and an integrated assessment of hormone-blood pressure relationships has not yet been undertaken. To clarify these interrelationships we monitored arterial pressure continuously, and From the

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Section: -supporting

confidence: 82%

Mechanisms in human renovascular hypertension.

Maslowski¹,

Nicholls²,

Espiner³

et al. 1983

Hypertension

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“…The hypertension seems to be more a function of the peripheral vasoconstrictor effects of A II and the renal effects of A II which promote sodium retention. 12 ' 18 In contrast to the data reported by McCaa et al, 11 in the present study, chronic infusion of A II VOL. 43, No.…”

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confidence: 70%

“…Finally, although circumstantial to the present study, prolonged infusions of A II under different experimental conditions might provide further insight into the role of the renin-angiotensin system in the long-term control of aldosterone secretion, particularly since it has been reported that chronic infusion of A II fails to produce a sustained increase in plasma aldosterone concentration in sodium-replete dogs. 11 Therefore, to generate quantitative data relating to the effects of excess aldosterone on arterial pressure, we infused aldosterone chronically into both adrenalectomized and intact dogs. Also, high levels of aldosterone were administered both in normal dogs and in dogs receiving A II given to suppress PRA and thus prevent changes in plasma levels of A II during the aldosterone infusion.…”

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confidence: 99%

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

Lohmeier¹,

Cowley²,

DeClue³

et al. 1978

Circulation Research

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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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“…The present observations have extended the analysis of angiotensin's role in sodium deficiency by blocking formation of the peptide in sodium-deprived rats. Infusion of the converting enzyme inhibitor can lead to increased plasma bradykinin levels, as well as the anticipated decrease in angiotensin II formation (33). However, no effects of bradykinin upon angiotensin-stimulated aldosterone production have been detected in isolated adrenal glomerulosa cells (unpublished observations) and there is no reason to believe that actions of bradykinin are involved in the present study.…”

Section: Discussionmentioning

confidence: 54%

Regulation of aldosterone secretion by the renin-angiotensin system during sodium restriction in rats.

Aguilera¹,

Catt²

1978

Proc. Natl. Acad. Sci. U.S.A.

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The role of angiotensin II as mediator of the aldosterone response to short periods of sodium restriction was studied in rats by administration of a converting enzyme inhibitor to block formation of the octapeptide throughout the duration of decreased sodium intake. In control animals, short-term sodium restriction caused increased levels of adrenal receptors for angiotensin II, with enhancement of early and late steps in aldosterone biosynthesis and elevation of plasma aldosterone concentration. Each of these changes induced by sodium deficiency was abolished during blockade of angiotensin II formation by continuous infusion of the converting enzyme inhibitor, SQ 14,225. The absolute dependence of adrenal glomerulosa cell responses on angiotensin H formation indicates that the renin-angiotensin system is the primary regulator of aldosterone secretion during physiological fluctuations in sodium intake.Although the importance of the renin-angiotensin system in the control of aldosterone secretion is well established (1-3), the precise role of angiotensin II in mediating the aldosterone response to sodium deficiency has been more difficult to define (4, 5). While it is generally agreed that the presence of the renin-angiotensin system is essential for the normal aldosterone response to sodium deficiency, there has been controversy about the nature and extent of the actions of angiotensin II as a proximate regulator of zona glomerulosa cells (4, 5). Thus, studies in sheep have suggested that factors other than angiotensin II are involved in the control of aldosterone secretion during sodium depletion and repletion (4).An important question remains about the physiological role of angiotensin II during reduced sodium intake, which is the most frequent stimulus for increased aldosterone secretion under normal conditions in most animal species. Here also a discrepancy has been noted, between the effect of angiotensin II infusions on aldosterone secretion in normal animals and the larger aldosterone responses caused by sodium deficiency (6, 7). However, the sensitivity of the adrenal to angiotensin II in several species increases during sodium restriction (8)(9)(10)(11)(12), and this could contribute to the relatively greater aldosterone secretion that accompanies the increased blood concentrations of angiotensin II during sodium deficiency.The interaction between angiotensin II and altered adrenal sensitivity during the aldosterone response to sodium restriction has been recently analyzed in rats. Initial studies showed that prolonged changes in electrolyte intake were accompanied by altered affinity and concentration of angiotensin II receptors in the rat adrenal (13). In more recent studies during short-term changes in sodium intake, salt restriction for as little as 36 hr increased angiotensin II binding and aldosterone responses inThe costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked "advertisement" in accordance with 18 ...

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Role of angiotensin II and potassium in the long-term regulation of aldosterone secretion in intact conscious dogs.

Cited by 43 publications

References 0 publications

Mechanisms in human renovascular hypertension.

Mechanisms in human renovascular hypertension.

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

Regulation of aldosterone secretion by the renin-angiotensin system during sodium restriction in rats.

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