Studies on the Mechanism of Aldosterone-Induced Hypertension in Man

Distler, A.; Just, H.; Philipp, Th.

doi:10.1042/cs0450743

Cited by 20 publications

(9 citation statements)

References 13 publications

(14 reference statements)

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“…The period after the cessation of spironolactone is a condition comparable to the early stage of aldosterone-induced hypertension. 24 Muscle SNA suppression by fludrocortisone is consistent with reports of decreased SNA found in patients with primary aldosteronism. 8 To exclude the possibility that the suppressed nerve activity observed in our study is an effect of time or repeated measurements, we included placebo studies in protocols 2 and 3.…”

supporting

confidence: 79%

Effects of fludrocortisone on sympathetic nerve activity in humans.

et al. 1994

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Fludrocortisone reduces plasma norepinephrine in healthy humans, but forearm vascular and pressor responses to norepinephrine are potentiated. The effects of fludrocortisone on sympathetic nerve activity in healthy humans are not known. To investigate these effects we evaluated muscle sympathetic nerve activity, heart rate, and arterial pressure in 11 healthy volunteers during three protocols: (1) before and on day 7 of fludrocortisone (0.4 mg/d) treatment with ad libitum diet (n=6); (2) before and on day 7 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n=7); and (3) before and on day 2 of fludrocortisone (0.4 mg/d) or placebo with a 150 mmol/24 h (mEq/24 h) sodium diet (n=4). Placebo did not alter any parameter. Fludrocortisone produced expected mineralocorticoid effects on hormones and electrolytes: (1) plasma renin activity decreased (P<.05) on the seventh day of fludrocortisone treatment with both diets (1.4±0.3 to 0.8±0.2 ng/mL per hour with ad libitum diet and 3.7± 1.2 to 1.3±0.7 ng/mL per hour with 150 mmol/24 h [mEq/24 h] sodium diet); (2) mean 24-hour urinary sodium excretion decreased during treatment (P<.05 day 4 versus day 0) and returned to baseline on day 7 (165±21, 137±31, and 174±30 mmol/24 h [mEq/24 h] with ad libitum diet and 132±18, 82+13, and 113±9 mmol/24 h [mEq/24 h] with 150 mmol/24 h [mEq/24 h] sodium diet on days 0, 4, and 7, respectively); and (3) after 2 days of treatment there was no change in plasma renin activity or 24-hour urinary sodium excretion. With ad libitum diet, fludrocortisone suppressed sympathetic nerve activity (18±4 to 6±3 bursts per minute, P<.05) and increased arterial pressure (90±4 to 96±3 mm Hg, P<.05) and body weight (77±3 to 79±3 kg, P<.05). With the 150 mmol/24 h (mEq/24 h) sodium diet, fludrocortisone also suppressed sympathetic nerve activity on day 2 (19±3 to 11 ±2 bursts per minute, P<.05) and day 7 (22±3 to 11±3 bursts per minute, P<.05). In contrast to the decrease in sympathetic nerve activity during fludrocortisone, arterial pressure and body weight did not change on either day 2 or 7, and plasma volume was increased only after 7 days of fludrocortisone (41 ±1 to 45±1 mL/kg, P<.05). This study demonstrates that fludrocortisone suppresses sympathetic nerve activity in humans and that this suppression may be related in part to factors other than increases in arterial pressure or plasma volume. nisms involved in the genesis and maintenance of mineralocorticoid hypertension, the role of the sympathetic nervous system is still unclear. In rats, most studies in the deoxycorticosterone acetate (DOCA)-salt model have shown evidence of increased sympathetic activity: (1) increased levels of circulating catecholamines, 1 (2) increased catecholamine synthesis and norepinephrine turnover rate in the heart, 2 and (3) augmented vasodepressor responses to ganglionic blockade. 3 In addition, chemical sympathectomy with centrally administered 6-hydroxydopamine prevents DOCA-salt hypertension. 4 Finally, direct recording of...

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supporting

confidence: 79%

Effects of fludrocortisone on sympathetic nerve activity in humans.

et al. 1994

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“…Both 9a-fluorocortisol administration to man (Distler & Philipp, 1976) and withdrawal of spironolactone in patients with primary aldosteronism (Distler, Just & Philipp, 1973) are associated with an initial increase in cardiac output, which then returns to control values.…”

Section: Discussionmentioning

confidence: 97%

Haemodynamic Response to Acth Administration in Essential Hypertension

Whitworth

Saines

Andrews

et al. 1981

Clin Exp Pharma Physio

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1. The haemodynamic and volume response to ACTH administration was investigated in six patients with mild, untreated essential hypertension and two patients with Addison's disease on maintenance steroids. Blood pressure, heart rate and weight were recorded daily. Plasma volume (125I-HSA) and cardiac output (thermo-dilution) were measured during the control period and on the 5th day of ACTH treatment. 2. In the hypertensive subjects, mean arterial pressure rose from 94.3 +/- 2.2 to 105.7 +/- 2.8 mmHg on the 5th day of ACTH administration (P less than 0.02). Plasma volume rose from 29.8 +/- 2.2 to 34 +/- 2.2 ml/kg. Cardiac index increased from 2.85 +/- 0.21 to 3.32 +/- 0.14 l/min per m2 (P less than 0.05). Cardiac output rose from 5.81 +/- 0.69 to 6.72 +/- 0.59 l/min. Calculated total peripheral resistance, heart rate and body weight were unchanged. No such changes were seen in patients with Addison's disease. 3. The haemodynamic characteristics of ACTH in patients with mild untreated essential hypertension are similar to those in the experimental model of ACTH induced hypertension in sheep.

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“…The increase in plasma volume results from a combination of glucocorticoid-induced redistribution of extracellular fluid and mineralocorticoid-induced sodium and water retention. Further evidence that the increase in CO probably depends on both mineralocorticoid and glucocorticoid effects are the findings in humans that CO increases during the early phase of primary aldosteronism 23 and during infusion of cortisol. 24 Furthermore, CO is elevated in canine deoxycorticosterone (DOC) 25 and deoxycorticosterone acetate (DOCA)-salt hypertension 26 and during DOCA-salt hypertension in rats.…”

Section: Discussionmentioning

confidence: 99%

Differential regional hemodynamic effects of corticotropin in conscious sheep.

Bednarik

May

1994

Hypertension

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The regional hemodynamic effects of 5 days of intravenous infusion of corticotropin (ACTH) (5 /xg/kg per day) were examined in conscious sheep (n=8). Mean arterial pressure increased from 81 ±2 to 93±3 mm Hg (/><.001) on day 2 of ACTH and remained at this level during the infusion. Cardiac output increased from 5.13±0.19 to 6.06±0.33 L/min (/ ) <.O1) because of an increase in stroke volume from 65±4 to 79±8 mL per beat (P<.01); heart rate remained unchanged. ACTH did not alter total peripheral conductance but had differential effects on regional conductances. Mesenteric conductance fell from 5.8±0.2 to a minimum of 4.9±0.3 (mL/min)/mm Hg (P<.05), and renal conductance increased from 3.5±0.3 to 4.6±0.3 (mL/min)/ mm Hg (P<.001). There was a small increase in iliac conductance (f<.05) and no change in coronary conductance. Mesenteric and iliac conductances fell progressively over 24 to 48 hours, whereas renal conductance increased rapidly after 3 hours of ACTH, reaching a maximum after 6 hours. Renal blood flow was increased during ACTH infusion from 278±18 to 403±23 mL/min (P<.001); mesenteric C orticotropin (ACTH) administration increases blood pressure in both humans 1 -3 and experimental animals. 46 In conscious sheep intravenous infusion of ACTH results in an increase in arterial blood pressure within 24 hours, which is sustained as long as ACTH is infused over a 5-to 10-day period. 7 ACTH hypertension can be reproduced by infusion of a combination of adrenocortical steroids and is dependent on the presence of the adrenal glands but not on intact adrenal innervation. 48 The hypertension is associated with an increase in plasma volume, without a significant change in extracellular fluid volume.9 A volume component of the hypertension is also suggested by the finding that the ACTH-induced rise in blood pressure can be modulated by alterations in sodium status. Long-term sodium loading magnifies the pressure rise produced by ACTH, and long-term dietary sodium restriction blunts the rise.10 " The hemodynamic profile of ACTH hypertension in conscious sheep is characterized by an elevated cardiac output (CO), with no change in total peripheral resistance. peripheral resistance to remain constant in the presence of renal vasodilatation, vasoconstriction must be occurring in other vascular beds. In the present study the effect of ACTH infusion on regional hemodynamics was examined in conscious sheep instrumented with electromagnetic flow probes to measure CO and with transittime flow probes to measure regional arterial blood flows. The aim of the study was to examine the regional hemodynamic effects of ACTH and to determine whether ACTH acts selectively to cause vasoconstriction in one vascular bed or whether the vasoconstriction is a more generalized phenomenon. MethodsMerino cross ewes (35-to 45-kg body weight), oophorectomized and with carotid artery loops, were housed in metabolism cages in association with other sheep. They were not used for at least 4 weeks after surgery until they were accustomed to ...

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Studies on the Mechanism of Aldosterone-Induced Hypertension in Man

Cited by 20 publications

References 13 publications

Effects of fludrocortisone on sympathetic nerve activity in humans.

Effects of fludrocortisone on sympathetic nerve activity in humans.

Haemodynamic Response to Acth Administration in Essential Hypertension

Differential regional hemodynamic effects of corticotropin in conscious sheep.

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