Dipyridamole decreases circulating renin-angiotensin system activity in hypertensive patients.

To study the effect of adenosine on renin release, n = 6 hypertensive patients, while on a constant 80 to 100 mEq/24 h Na+ diet, received oral 150 mg dipyridamole (an adenosine uptake inhibitor) three times daily for 3 days while upright plasma renin activity (PRA) and plasma aldosterone, urinary aldosterone, plasma and urinary Na+,K+, and creatinine clearance were monitored the day before (basal) the first and third day of the treatment and the day after the withdrawal (recovery). As compared to basal and to recovery, dipyridamole significantly decreased PRA, and plasma and urinary aldosterone without affecting plasma and urinary Na+ and K+, creatinine clearance, blood pressure, and heart rate. These data, showing that dipyridamole decreases PRA and aldosterone, confirm also in hypertensives that endogenous adenosine inhibits the circulating renin-angiotensin-aldosterone system.     

Central dopaminergic regulation of aldosterone secretion in sheep

Central dopaminergic mechanisms involved in the regulation of plasma aldosterone concentration were investigated in 16 conscious sheep following Na depletion with intramuscularly administered furosemide. Intracerebroventricular infusion of dopamine (20 micrograms/min) decreased plasma aldosterone significantly to 52 +/- 8% of basal level and increased plasma renin activity (PRA) significantly to 172 +/- 25% of basal level in this animal model. In addition, intracerebroventricular infusion of the dopamine antagonist metoclopramide (20 micrograms/min) in artificial cerebrospinal fluid vehicle significantly increased aldosterone levels to 144 +/- 14% of basal level and decreased PRA to 62 +/- 5% of basal value. Neither intracerebroventricular infusion of the vehicle nor intravenous infusions of metoclopramide or dopamine at the same doses changed aldosterone or PRA levels. Intracerebroventricular bolus injections of metoclopramide (20 micrograms/kg in 0.4 ml of vehicle) were also effective, increasing aldosterone levels to 266 +/- 22% of basal level and decreasing PRA to 70 +/- 12% of basal level. Intravenous bolus injections of the same dose of metoclopramide were ineffective. Dopamine was infused intracerebroventricularly into two uniadrenalectomized sheep with the remaining adrenal transplanted to the neck. Aldosterone levels were decreased to 49 +/- 10% of basal level, and PRA was increased to 157 +/- 10% of basal value. None of the infusions or injections changed arterial or intracranial pressure, or plasma K, Na, and cortisol levels. These data indicate that endogenous or exogenous dopamine may act on central dopamine receptors to decrease plasma aldosterone concentration by an unknown humoral mechanism. The known aldosterone regulators, plasma Na, K, angiotensin II, and adrenocorticotropic hormone, are not involved in the regulation.     

尿醛固酮在原发性醛固酮增多症筛查中的价值及钠摄入对其筛查效率的影响

目的探讨尿醛固酮在原发性醛固酮增多症(PA)筛查中的作用并评估钠盐摄入对其筛查效率的影响。方法收集2006-09-2009-07中山大学附属第二医院内分泌科门诊和住院的高血压患者269例,其中包括原发性高血压患者237例(女119例,男118例,平均年龄47.4岁)和PA患者32例(女20例,男12例,平均年龄41.9岁)。所有入组的研究对象均测定立位1h血清醛固酮(SAC)和血浆肾素活性(PRA),并留取24h尿检测尿醛固酮、尿钠和尿钾。通过构建受试者工作特征曲线(ROC),评估尿醛固酮在PA筛查中的效率并确定最佳切点。以尿钠/尿钾作为钠盐摄入的评估方法,以尿钠/尿钾中位数作为切点将原发性高血压组分为高尿钠/尿钾组(n=119)和低尿钠/尿钾组(n=118),分别以这两组高血压人群作为阴性人群,以PA组作为阳性人群进行ROC分析,比较不同钠盐摄入情况对尿醛固酮水平及其PA筛查效率的影响。结果通过构建ROC曲线评估尿醛固酮在PA筛查中的作用,其曲线下面积为0.824(95%CI0.773～0.867,P<0.01),应用Youden’s指数确定尿醛固酮诊断PA的最佳切点值为11.6μg/24h,其敏感性和特异性分别为81.2%(95%CI63.3%～92.7%)和74.3%(95%CI68.2%～79.7%);在原发性高血压患者中,尿醛固酮与尿钠/尿钾呈负相关(r=-0.174,P<0.01)。高尿钠/尿钾组尿醛固酮、SAC和PRA水平明显低于低尿钠/尿钾组。结论尿醛固酮在PA筛查有一定意义,采用11.6μg/24h作为切点可取得较高的筛查效率。钠摄入可影响尿醛固酮水平,但不影响其筛查效率。     

Increase in plasma concentrations of atrial natriuretic peptide during infusion of hypertonic saline in conscious newborn calves

Plasma concentrations of atrial natriuretic peptide (ANP), plasma renin activity (PRA), plasma concentrations of aldosterone, urine flow rate and sodium and potassium excretion were studied in two groups of four conscious 3-day-old male calves, infused with hypertonic saline or vehicle. Hypertonic saline infusion (20 mmol NaCl/kg body weight) was accompanied by a progressive rise in plasma concentrations of ANP (from 16.5 +/- 0.2 pmol/l at time 0 to 29.3 +/- 3.0 pmol/l at 30 min; P less than 0.05) and by a gradual decrease in PRA (from 1.61 +/- 0.23 nmol angiotensin I/l per h at time 0 to 0.54 +/- 15 nmol angiotensin I/l per h at 90 min; P less than 0.05); there was no change in the plasma concentration of aldosterone. Within the first 2 h of the 24-h urine collection period there was a marked rise in urine flow rate and sodium excretion in treated calves when compared with control animals (66.0 +/- 8.3 vs 15.9 +/- 1.2 ml/kg body weight per 2 h (P less than 0.05) and 6.7 +/- 1.3 vs 0.4 +/- 0.02 mmol/kg body weight per 2 h (P less than 0.01) respectively). During the following 22 h, urinary water and sodium excretion remained at significantly high levels. Thus, in the conscious newborn calf, changes in plasma ANP levels and urinary water and sodium excretion during hypertonic saline infusion are compatible with the hypothesis that endogenous ANP participates, at least in part, in the immediate diuretic and natriuretic renal response induced by the sodium overload.     

Contributions of central sympathetic neural activity to furosemide-induced increases in plasma renin activity and noradrenaline

To evaluate the role of the central nervous system on the furosemide-induced increases in plasma noradrenaline (PNA), renin activity (PRA), and aldosterone concentration (PAC), central vasoactive sympathetic structures were inhibited by intravertebral artery infusion of colnidine. Intravertebral artery infusion of clonidine (0.06 microgram/Kg/min) significantly reduced basal PNA, heart rate, and arterial pressure, while both PRA and PAC were increased. Intravenous infusion of the same dose of clonidine caused no significant changes in PNA, PRA, and PAC. Intravertebral artery infusion of clonidine (0.02 or 0.1 microgram/Kg/min) significantly suppressed the furosemide-induced increases in PNA and heart rate, and induced a drop in arterial pressure. Although the furosemide-induced increase in PRA was suppressed by intravertebral artery infusion of clonidine, the furosemide-induced increase in PAC was not affected. These results suggest that the furosemide-induced increase in PNA may be mediated by the central sympathetic nervous system and that some of the furosemide-induced increase in PRA may be mediated by central sympathetic neural activation.     

The Effects of Acth on the Renin-Aldosterone System in Normotensive Man

The present study examined the effects of low dose ACTH administration (0.1 mg/day for 2 days) on plasma renin concentration, (PRC), activity (PRA) and substrate (PRS), cortisol and aldosterone in man. Six healthy male volunteers on a diet calculated to contain 150 mmol Na/day received an infusion of 5% dextrose (6 ml/h) for 24 hours, then ACTH (Synacthen, Ciba-Geigy) was added to the infusion at the rate of 100 μg per day, for 48 h. Blood samples were taken four hourly for determination of plasma cortisol aldosterone, PRC, PRA and PRS. There was a highly significant increase in plasma cortisol and aldosterone concentrations during ACTH infusion compared with dextrose infusion, but no significant increase in active or inactive PRC, PRA or PRS. In a separate study of 15 healthy male volunteers, dexamethasone (1 mg at 2300 h) suppressed plasm a cortisol but had noeffecton PRC. These results do not support the view that stimulation of aldosterone by ACTH ismediated through the renin angiotensin system.     

Pseudohypoaldosteronism: multiple target organ unresponsiveness to mineralocorticoid hormones.

The first report of a 7-month-old male with pseudohypoaldosteronism in which unresponsiveness to mineralocorticoids has been demonstrated in the kidney, colon, and sweat and salivary glands is presented here. This is documented by urinary, salivary, and sweat sodium wasting in the presence of elevated urinary aldosterone excretion, plasma aldosterone concentration, and PRA. There was no mineralocorticoid response in the kidney or salivary or sweat glands to the administration of high doses of 9 alpha-flurocortisol. Furthermore, in this patient, the colonic mucosal cells failed to respond to exogenous aldosterone administration. Repeat evaluation at 25 months of age showed persistence of the sodium wasting and multiple target organ insensitivity to administered mineralocorticoid. Since this patient has defective mineralocorticoid response in the major sodium-conserving organs, the only therapy possible was administration of sodium to compensate for total sodium loss.     

1,25-Dihydroxycholecalciferol regulates salivary phosphate secretion in cattle

The influence of 1,25-dihydroxycholecalciferol (1,25-(OH)2D3) on salivary inorganic phosphorus (Pi) concentration and secretion was studied in two groups of four heifers, the right parotid ducts of which were chronically fitted with a re-entrant cannula. In four heifers i.v. Pi loading (5 mmol/min for 2 h) induced hyperphosphataemia associated with a decrease in plasma 1,25-(OH)2D concentration and an increase in salivary Pi concentration and secretion. In four other heifers, daily 1 alpha-hydroxycholecalciferol injections (1 microgram/kg body wt per day for 3 days) induced hyperphosphataemia associated with an increase in plasma 1,25-(OH)2D concentration and a decrease in salivary Pi concentration and secretion. These treatments had no significant effect on salivary calcium concentration and secretion. Our results indicate that plasma 1,25-(OH)2D concentrations rather than phosphataemia regulate salivary Pi concentration and secretion in cattle.     

The effect of sodium depletion and potassium loading on cortisol induced hypertension in sheep

Glucocorticoid induced hypertension has been regarded as independent of sodium (Na), in contrast to mineralocorticoid induced hypertension, which is Na+-dependent. These studies compare the effect of Na+ depletion and potassium (K+) loading on glucocorticoid hypertension induced by cortisol in conscious sheep. Cortisol (480 mg/d) for 5 days, in sheep on a normal chaff diet (90-140 mmol/d Na+, 200-250 mmol/d K+) increased mean arterial pressure by 18 mmHg on day 5, increased plasma Na+ concentration, reduced plasma K+ concentration, and did not change urinary Na+ excretion. Following Na+ depletion (Na+ loss 603 +/- 49 mmol), cortisol increased mean arterial pressure from 70 +/- 1 mmHg to 76 +/- 3 mmHg on day 5 (P less than 0.001) and the increase in pressure was significantly less than the increase seen on the normal diet (P less than 0.05). Plasma Na+ increased and plasma K+ decreased. Urinary Na+ and K+ excretion was unchanged. KCl loading (700-900 mmol/day) for 10 days had no effect on the maximum rise in mean arterial pressure (+18 mmHg with cortisol in K+ loaded sheep). Plasma Na+ and K+ fell, and urinary Na+ excretion increased during the infusion. These studies show that Na+ depletion, but not KCl loading, reduced cortisol induced hypertension in sheep. These data show that glucocorticoid hypertension is not independent of Na+ status.     

Reduction of erythrocyte (Na(+)-K+) ATPase activities in non-insulin-dependent diabetic patients with hyperkalemia.

To elucidate the mechanism of hyperkalemia in diabetic patients without renal failure, we investigated (Na(+)-K+) adenosine triphosphatase (ATPase) activity in erythrocyte membrane, erythrocyte Na+ and K+ content, and plasma endogenous digitalis-like substance in control subjects (n = 16) and non-insulin-dependent diabetes mellitus (NIDDM) patients (n = 62). NIDDM patients were divided into normokalemic patients (NKDM, n = 48) and hyperkalemic patients (HKDM, n = 14). There was no difference in plasma glucose or hemoglobin A1c (HbA1c) levels, plasma renin activity (PRA), and plasma aldosterone concentrations (PAC) between NKDM and HKDM patients. (Na(+)-K+)ATPase activities in NIDDM patients were significantly reduced compared with those in control subjects (0.336 +/- 0.016 mumol-inorganic phosphate [Pi]/mg protein/h, mean +/- SEM, P less than .05), and (Na(+)-K+)ATPase activities in HKDM patients (0.243 +/- 0.015 mumol Pi/mg protein/h) were significantly reduced compared with those in NKDM patients (0.295 +/- 0.008 mumol Pi/mg protein/h, P less than .01). Plasma K+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in diabetic patients (r = -.365, P less than .01). Erythrocyte Na+ content had a significant negative correlation with (Na(+)-K+)ATPase activity in control subjects (r = -.619, P less than .05). There was no difference in plasma endogenous digitalis-like substance among the three groups. (Na(+)-K+)ATPase activity was not significantly correlated with plasma endogenous digitalis-like substance in control subjects and diabetic patients. These findings suggest that the reduction of (Na(+)-K+)ATPase activity, which was not related to plasma digitalis-like substance, may be partly responsible for hyperkalemia in diabetic patients.     

Interrenal function in larval Ambystoma tigrinum. I. Responses to alterations in external electrolyte concentrations

Larval Ambystoma tigrinum were acclimated to distilled water, 150 mM NaCl, or 100 mM KCl to alter electrolyte balance. The effects on electrolyte balance and circulating interrenal steroids were observed by analysis of plasma and urine samples. Steroid titers were measured by radioimmunoassay. Acclimation to distilled water decreased plasma and urinary [Na+] and elevated circulating aldosterone (sixfold) and corticosterone (45%) but did not affect cortisol. Larvae acclimated to 150 mM NaCl experienced increases in plasma and urinary [Na+]. In this group aldosterone titer was depressed (47%), corticosterone was elevated (100%), and cortisol was unchanged. Salamanders acclimated to 100 mM KCl increased plasma and urinary [K+] and shifted to net renal K+ secretion. This group elevated aldosterone (150%); however, corticosterone was not significantly affected. Reciprocity between the Na+-loaded and K+-loaded groups was observed. Acclimation to high potassium stimulated fractional renal Na+ reabsorption while Na+ loading stimulated fractional K+ reabsorption. These findings are consistent with aldosterone having opposite effects on renal Na+ and K+ transport, stimulating the reabsorption of the former and the net secretion of the latter.     

Blood pressure, renal and endocrine responses to alpha-human atrial natriuretic polypeptide in healthy volunteers

Intravenous infusion of graded doses of alpha-human atrial natriuretic polypeptide (alpha-hANP) resulted in a dose-dependent decrease in blood pressure and an increase in heart rate in 11 healthy male volunteers. However, there were no significant changes in urine output or in the urinary excretion rate of sodium. Glomerular filtration rate did not change, while renal blood flow decreased, leading to significant increases in filtration fraction and renal vascular resistance. Although plasma renin activity (PRA) and plasma concentration of norepinephrine (PNE) increased during infusion of alpha-hANP (both p less than 0.001), plasma concentrations of aldosterone (PA) and cortisol (PC) decreased (both p less than 0.001). Plasma concentration of arginine vasopressin (PAVP) did not change during the infusion, but greatly increased after cessation of the infusion. The hematocrit increased slightly, but significantly, during the infusion. These results show that, although alpha-hANP has a potent hypotensive action and inhibits the secretion of aldosterone, cortisol, and probably arginine vasopressin, it does not dilate renal vessels in normotensive persons, and likely increases vascular permeability. The lack of consistent diuretic and natriuretic responses to alpha-hANP may be related to the predominance of the hypotensive effect over the renal effects of the peptide in normotensive persons, or a diurnal change may have served to obscure such a response.     

Effects of maternal sodium depletion on the composition of ovine fetal fluids

Effects of maternal sodium depletion on the composition of ovine fetal fluids were studied. Maternal Na depletion was achieved by 48-h drainage of parotid saliva. There was a significant decrease in both maternal and fetal plasma Na concentration, indicating that both mother and fetus had experienced the Na-depletion stimulus. There was a significant increase in maternal blood aldosterone but the change in fetal blood aldosterone was not significant. In animals where there was an increase in fetal blood aldosterone the increase could be accounted for by transfer of aldosterone across the placenta from the mother. There was a significant decrease in fetal urinary Na concentration and Na excretion and the urinary Na/K ratio fell in seven out of eight studies. These observations are consistent with the hypothesis that fetal Na depletion sensitizes the fetal kidney to the action of circulating aldosterone as in the adult.     

beta-Endorphin stimulates plasma renin and aldosterone release in normal human subjects

To determine the effect of beta-endorphin on the renin-angiotensin-aldosterone system, human synthetic beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg X min) was infused iv in normal subjects. Each dose was administered for 30 min, and a control infusion of 5% dextrose and water was given on another day. Ten subjects were studied recumbent and in balance while ingesting a 10-meq Na+ diet. Plasma renin activity (PRA), plasma aldosterone (PA), and plasma cortisol (F) were measured basally and every 30 min for 210 min. The increments in PRA and PA above basal significantly (P less than 0.05) increased (3.1 +/- 1.2 ng/ml X h and 12.2 +/- 5.3 ng/dl, respectively; P less than 0.05) at the end of the beta-endorphin infusion. beta-Endorphin also significantly (P less than 0.01) suppressed F levels. Since in the low salt study, beta-endorphin suppressed F release while stimulating renin secretion, an additional five subjects were pretreated with dexamethasone (0.5 mg every 6 h) and were studied in balance while ingesting a 200-meq Na+ diet to suppress the renin-angiotensin system. Significant (P less than 0.025) increments in PRA (2.1 +/- 0.7 ng/ml X h) and PA (4.1 +/- 1.7 ng/dl) levels above basal were again found during the sequential dose infusion of beta-endorphin (0.3, 1.0, and 3.0 micrograms/kg X min). However, PA elevations were sustained for at least 120 min after the beta-endorphin infusion was stopped despite a drop in PRA 90 min earlier. In additional studies, an attempt was made to define the minimal effective dose of beta-endorphin by 60-min infusions (0.03, 0.1, and 0.3 micrograms/kg X min) in subjects on a 200-meq Na+ diet who were dexamethasone pretreated. The PRA and PA levels rose significantly (P less than 0.05) above basal at the 0.3 micrograms/kg X min dose, but not at the 0.03 or 0.1 micrograms/kg X min dosage levels. There were no changes in blood pressure or potassium during either the 10 or 200-meq Na+ studies. Thus, beta-endorphin stimulates aldosterone release in vivo. However, the underlying mechanisms are complex, since renin levels also increased. The data suggest that the early aldosterone rise may be secondary to an increase in renin release, but renin cannot account for the sustained postinfusion elevations of aldosterone.     

Nocturnal oscillations of plasma aldosterone in relation to sleep stages

This study examined the relationship between aldosterone secretion and sleep stages in conjunction with two aldosterone regulating hormone systems, the renin-angiotensin system (RAS) and adrenocorticotropin (ACTH), and also K+. Nocturnal plasma patterns of aldosterone, plasma renin activity (PRA), ACTH and K+ were established in blood collected at 10-min intervals in two groups of 6 subjects. Both groups underwent two 9 hour overnight-studies, consisting of one control night and one experimental night. The first group was maintained on a low Na diet and the other was given a beta-blocker, atenolol. Polygraphic recordings of sleep were scored according to established criteria. For the control night, REM sleep usually began at peak level or in the descending phase of aldosterone oscillations. As previously described, PRA reflected REM-NREM sleep alteration, levels increased in NREM and decreased during REM sleep. ACTH fluctuations did not oscillate with sleep stages, but levels were very seldom in the ascending phase at REM sleep onset. Plasma K+ remained almost constant throughout the night. The relative importance of the ACTH and the RAS on nocturnal aldosterone secretion and the relationship between aldosterone oscillations and sleep stages remained unclear. Modulating renin levels by either consuming a low Na diet or administration of a beta-blocker enabled this relationship to be clarified. The RAS dominated aldosterone secretion when stimulated by a low sodium diet. Aldosterone oscillations then reflected PRA oscillations with a delay of about 20 min and the relationship of aldosterone to sleep stages was dependent on the relationship of PRA with sleep stages.(ABSTRACT TRUNCATED AT 250 WORDS)     

Vascular responses to ouabain and norepinephrine in low and normal renin hypertension

A circulating Na+, K+-ATPase inhibitor may cause arterial hypertension in patients with suppressed plasma renin activity, either directly or by sensitizing peripheral vessels to alpha-adrenergic stimulation. This hypothesis was tested by evaluating forearm arteriolar (plethysmographic technique) response to exogenous alpha-adrenergic stimulation by a 2-minute intra-arterial infusion of norepinephrine (0.1 microgram/dl tissue per minute) and to Na+, K+-ATPase inhibition by sequential 20-minute intra-arterial infusions of ouabain (0.36 and 0.72 microgram/dl tissue per minute). Two groups of hypertensive subjects with suppressed plasma renin activity, either essential or secondary to aldosterone excess, were compared with age-matched and sex-matched hypertensive subjects with normal plasma renin activity (n = 7 per group). No significant differences in forearm vascular response to norepinephrine were found among the three groups. Ouabain caused a highly significant, dose-related increment in forearm vascular resistance that was not accompanied by changes in the contralateral limb or systemic blood pressure. No significant interindividual differences in vascular responsiveness to ouabain were found. The individual increments in forearm vascular resistance during ouabain administration were unrelated to basal values or to plasma aldosterone, norepinephrine, or potassium concentrations. These data are not consistent with the hypothesis that suppressed basal Na+, K+-ATPase activity is primarily a characteristic of hypertensive patients with unresponsive plasma renin activity. Overall, these results cast doubts on the possibility of linking the development of human low renin hypertension to an endogenous Na+, K+-ATPase inhibitor.     

Action of L-epinephrine on the renin-aldosterone system and on urinary electrolyte excretion in man

The effect of L-epinephrine infusions (0.5–6.5 μg/min for up to 24 hr) in recumbency, on the renin-aldosterone system was studied in normal volunteers on diets containing 200 mEq sodium. Urinary sodium excretion was increased, potassium excretion was decreased, aldosterone excretion was suppressed while blood pressure and heart rate were minimally affected by epinephrine (1 μg/min). Inulin and para-aminohippurate clearances changed transiently and slightly during epinephrine infusions over 10 hr in normal subjects. In separate experiments, epinephrine lowered serum K, raised serum Na, raised plasma renin activity and, usually, lowered plasma aldosterone concentrations. There was an excellent correlation between epinephrine-induced changes in serum K and plasma aldosterone concentrations (r = +0.85, p < 0.001). Significant dose-response relationships were found between L-epinephrine infusion rates of 0.5–6.5 μg/min and observed serum K concentrations. We conclude that L-epinephrine infusions at rates probably well within the physiological range, induce hypokalemia (by increased cellular uptake of K) which lowers aldosterone secretion despite concomitant elevation of PRA and causes natriuresis for up to 24 hr.     

Long term evolution of glucocorticoid-suppressible hyperaldosteronism

It is generally held that idiopathic hyperaldosteronism and glucocorticoid-suppressible hyperaldosteronism (GSH) are distinct entities, distinguishable by thorough investigation. We report a patient who presented in 1974 at age 15 yr with blood pressure of 240/120 mm Hg, serum K of 3.1 mM, low renin, and high normal aldosterone excretion, with findings diagnostic of GSH. After dexamethasone treatment (2 mg/day for 4 weeks), urinary aldosterone was undetectable (less than 1 microgram/24 h), associated with correction of hypertension and hypokalaemia. While untreated, plasma aldosterone increased in response to ACTH infusion at a dose that did not influence plasma cortisol. Plasma aldosterone at 0800 h while recumbent was higher than in subsequent samples taken while ambulant, consistent with ACTH dependence of aldosterone secretion. Blood pressure, renin, and potassium remained normal for 4 yr during treatment with dexamethasone (0.5-0.75 mg/day), but hypertension then slowly returned. After 7 yr, the original studies were repeated. Urinary aldosterone excretion was again in the high normal range after 3 weeks of no treatment, but both plasma renin and aldosterone consistently increased in response to upright posture. After dexamethasone treatment (2 mg/day) for 4 weeks, urinary aldosterone was not suppressed (excretion rate, 10.8, 9.2, and 5.7 micrograms/day; urinary Na, greater than 100 mmol/day; urinary cortisol, less than 1 microgram/day). At this time, dexamethasone did not alleviate hypertension or increase renin. Control of blood pressure has been readily achieved, 8-12 yr after diagnosis, with a low dose of beta-adrenergic antagonist and amiloride. Aldosterone remains incompletely suppressible during sodium loading, so that the findings now resemble those of idiopathic hyperaldosteronism. This sequence indicates that glucocorticoids may not permanently control hypertension in GSH. The transient dominance of ACTH in control of aldosterone secretion indicates that the relationship between GSH and idiopathic hyperaldosteronism merits further evaluation in long term studies.     

Blocking T-type Ca2+ channels with efonidipine decreased plasma aldosterone concentration in healthy volunteers.

Efonidipine can block both L- and T- type Ca2+ channels. In a previous in vitro study, we clarified that efonidipine dramatically suppresses aldosterone secretion from human adrenocortical tumor cells during angiotensin II (Ang II)- and K+-stimulation, whereas nifedipine, a dominant L-type Ca2+ channel antagonist, does not. This study was conducted to assess the in vivo effects of efonidipine and nilvadipine on the plasma aldosterone concentration. Placebo, 40 mg of efonidipine, or 2 mg of nilvadipine was administered to five healthy male volunteers. Hemodynamic parameters (pulse rate [PR] and blood pressure [BP]), plasma concentrations of neurohormonal factors (plasma renin activity, Ang II, aldosterone, and adrenocorticotropic hormone [ACTH]), and serum concentrations of Na+ and K+ were measured before and 6 h after administration of the agents. All three agents had little effect on PR and BP. Efonidipine and nilvadipine significantly increased plasma renin activity and Ang II. Both had little effect on ACTH, Na+, and K+. The plasma aldosterone concentration was significantly decreased after efonidipine treatment (88.3 +/- 21.3 to 81.6 +/- 24.9 pg/ml, p = 0.0407), whereas it was significantly increased after nilvadipine treatment (66.5 +/- 12.2 to 82.17 +/- 16.6 pg/ml, p = 0.0049). Placebo had little effect on neurohormonal factors. Efonidipine decreased plasma aldosterone concentration despite the increase in plasma renin activity and Ang II, suggesting that T-type Ca2+ channels may also play an essential role in the secretion of aldosterone in healthy human volunteers.     

Effects of low-dose epinephrine infusion on cardiovascular and renal responses to water immersion in humans

Elevated plasma epinephrine concentrations may impair blood pressure homeostasis and renal sodium and volume excretion in response to central hypervolemia. We studied the effects of a low-dose epinephrine infusion (12 ng/kg/min) on cardiovascular and renal responses to a thermoneutral head-out water immersion in eleven healthy men.Responses to water immersion without epinephrine were characterized by significant suppression of plasma renin activity (PRA), plasma aldosterone concentration, and renal norepinephrine excretion, and an augmentation of natriuresis and diuresis. Epinephrine infusion, which raised mean plasma epinephrine concentration 4.3-fold, slightly increased plasma norepinephrine and renal norepinephrine excretion, markedly stimulated PRA (+66.7%), but decreased plasma aldosterone (−11.7%), and augmented renal sodium and volume excretion. Despite the presence of the epinephrine infusion, water immersion continued both to suppress PRA and aldosterone, and to increase natriuresis and diuresis in a qualitatively similar pattern. During all conditions blood pressure and heart rate remained unchanged.It is concluded that physiologic responses to central hypervolemia are not impaired at stress levels of circulating epinephrine. During epinephrine infusion, despite a concomitant increase in plasma norepinephrine and a stimulation of PRA, blood pressure remained constant in response to water immersion due to an augmentation of natriuresis and diuresis.