Biomedical subjects

R M Carey

Publications and source records attributed to R M Carey.

At least 19 recordsLinked to original sources

PubMed1992

Temporal pattern of renin and aldosterone secretion in men: effects of sodium balance.

To investigate the pulsatile nature of basal and stimulated renin and aldosterone secretion, we sampled blood for plasma renin activity (PRA) and plasma aldosterone concentration at 10-min intervals for 24 h in nine normal supine human male subjects after equilibration in high- and low-sodium balance states. We evaluated serial hormonal measures by a quantitative waveform-independent deconvolution technique designed to compute the number, amplitude, and mass of underlying secretory bursts and simultaneously to estimate the presence and extent of basal secretion. For both PRA and aldosterone: 1) burstlike release accounted for greater than or equal to 60% of total secretion and tonic release for less than 40%; 2) there was an 80- to 85-min interpulse interval unchanged by sodium intake; 3) sodium restriction engendered an increase in plasma hormone concentrations by increasing the amount and maximal rate of hormone secreted per burst; 4) low dietary sodium also induced increases in basal hormone secretory rates, suggesting that there may be two regulatory processes driving renin and aldosterone secretion; and 5) PRA was significantly coupled to plasma aldosterone concentration by a 0-, 10-, or 20-min aldosterone lag time in both high- and low-sodium balance. We conclude that both renin and aldosterone are released via a predominantly burstlike mode of secretion; PRA and plasma aldosterone concentrations are positively coupled by a short time lag (0-20 min); and sodium restriction achieves an increase in mean PRA and plasma aldosterone concentration by selective amplitude enhancement of individual hormone secretory bursts and by increased tonic (interburst) basal secretory rates.

Adult↗

PubMed1992

Intrarenal DA2 dopamine receptor stimulation in the conscious dog.

DA2 dopamine receptors are present in renal blood vessels and glomeruli. Stimulation of DA1 dopamine receptors leads to renal vasodilation, diuresis, and natriuresis, but a functional role for renal DA2 receptors is largely unknown. We investigated the possible role of DA2 receptors in the control of renal function by intrarenal infusion of a highly specific DA2 agonist, LY 171555 (LY), in conscious uninephrectomized dogs (n = 5) in metabolic balance at sodium intake of 40 meq/day. The infusion of LY at 0.5 pmol.kg-1.min-1 did not change the urinary sodium excretion or renal hemodynamic function. A significant dose-dependent antidiuresis (F = 8.1, P less than 0.0001) and antinatriuresis (F = 93.3, P less than 0.0001) and a decrease in filtration fraction (F = 2.3, P less than 0.02) occurred as the LY dose was increased from 1.0 to 10.0 pmol.kg-1.min-1. There were no changes in systemic plasma renin activity, plasma aldosterone concentration, or mean arterial pressure during intrarenal LY administration. These data suggest that intrarenal DA2 receptor stimulation with LY decreases renal sodium excretion in part by hemodynamic mechanisms. Renal dopamine may act at vascular and/or glomerular DA2 receptors to modulate renal function.

Animals↗

PubMed1992

Colocalization and release of angiotensin and renin in renal cortical cells.

Angiotensin is generated within the kidney, but the precise loci for the formation of angiotensin I (ANG I) and angiotensin II (ANG II) have not been demonstrated. We performed electron microscopy immunocytochemistry in kidney sections of 10-day-old (newborn) and adult Wistar-Kyoto (WKY) rats using specific antibodies to renin, ANG I, ANG II, and angiotensinogen (AO). Renin, ANG I, ANG II, and AO were present in juxtaglomerular (JG) cells. Renin was largely confined to cytoplasmic granules; ANG I and ANG II were colocalized to these granules but also were present in the cytoplasm; AO was distributed throughout the cytoplasm. AO also was present in a renal cortical distribution in proximal tubular cells. Northern blot analysis demonstrated AO mRNA in total kidney and liver but not in renal microvessels. Using the reverse hemolytic plaque assay, we demonstrated release of ANG I and renin from individual renocortical cells of adult WKY rats. Under control conditions, the number of releasing cells was 11 +/- 1 for ANG I and 10 +/- 1 for renin. Addition of rat renin inhibitor (RI) (1 x 10(-5) M), which inhibited renin activity in the medium from 37 to 9 pg ANG I.ml-1.h-1, did not alter ANG I plaque number. Addition of rat AO increased ANG I plaque number to 17 +/- 2 (P less than 0.05). Incubation with both RI and AO prevented the increase in ANG I plaque number obtained with AO alone. Enalapril treatment (7 days; n = 5) increased the number of plaque-forming cells to 22 +/- 2 for ANG I (P less than 0.0005) and to 39 +/- 7 for renin (P less than 0.001). The results suggest an intracellular location for AO and angiotensin and release of renin and ANG I by renal cortical cells and suggest that released angiotensin is produced intracellularly and that secretion of ANG I is augmented by converting enzyme inhibition.

Angiotensin I↗

PubMed1992

Distribution and content of renin and renin mRNA in remnant kidney of adult rat.

To determine whether kidney hypertrophy secondary to reduction of renal mass affects the intrarenal distribution and concentration of renin mRNA and its protein, adult male Sprague-Dawley rats were studied 4 wk after sham operation (Sham, n = 10), uninephrectomy (UNX, n = 14), or five-sixths nephrectomy (5/6 NX, n = 12). Left kidney weight-to-body weight ratio (x10(3)) was higher in 5/6 NX (6.6 +/- 0.2) than in UNX (4.5 +/- 0.2) or Sham (3.8 +/- 0.1) groups (P < 0.001). The percentage of juxtaglomerular apparatuses (%JGA) containing renin was lower in 5/6 NX (32 +/- 5) than in UNX (56 +/- 2, P < 0.001) or Sham (50 +/- 1, P < 0.05) groups. Renal renin mRNA concentrations (pg renin mRNA/microgram total RNA) detected by radiodensitometric renin mRNA dot-blot assay were lower in 5/6 NX (1.8 +/- 0.3) than in UNX (13.2 +/- 1) or Sham (14.2 +/- 1.1, P < 0.001). In situ hybridization histochemistry demonstrated that in all groups of rats renin mRNA was confined to the JGA. However, the hybridization signals (grains/JGA) were less intense in 5/6 NX (211 +/- 24) than in UNX (486 +/- 35) or Sham (541 +/- 40) groups (P < 0.001). Renal renin concentration (ng angiotensin I.mg protein-1.h-1) tended to be lower in 5/6 NX (20 +/- 15) than in UNX (44 +/- 7.8) or Sham (60.8 +/- 10) groups. In addition, plasma renin activity (ng.ml-1.h-1) was lower in 5/6 NX (3.8 +/- 0.6) than in UNX (8.8 +/- 1.8, P < 0.05) or Sham (14.3 +/- 2, P < 0.001) groups.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Expression of alpha-smooth muscle actin in the developing kidney vasculature.

To determine whether alpha-smooth muscle (alpha-SM) isoactin is expressed in the maturing kidney as well as the changes associated with maturation, we processed for immunocytochemistry kidney sections from Wistar-Kyoto rats at various prenatal (15, 17, 19, and 20 days) and postnatal (2, 5, 10, 15, and 90 days) ages using a monoclonal anti-alpha-SM actin antibody. At 15 days of gestation, only a few mesenchymal cells contained alpha-SM actin. However, other fetal vasculature structures (heart, aorta, peripheral blood vessels) expressed alpha-SM actin. Vascular localization was first observed at 17 days of gestation in larger corticomedullary vessels. As maturation progressed, actin expression accompanied the outward growth and branching of the kidney vasculature. During fetal life (17 days), alpha-SM actin also was expressed within juxtamedullary glomeruli. As the centrifugal maturation of nephrons proceeded, intraglomerular expression extended to outer cortical glomeruli. After 10 days of postnatal life, once glomerular development was completed, intraglomerular expression was no longer present. Peritubular capillaries expressed alpha-SM actin during early (fetal and neonatal) development, but not in the adult kidney. We conclude that 1) expression of alpha-SM actin in the developing kidney is delayed with respect to other vascular beds, 2) expression of alpha-SM actin follows the centrifugal pattern of nephrovascular development, and 3) glomerular and peritubular capillary expression of alpha-SM actin is a transient developmental phenomenon associated with active glomerulogenesis and capillary growth.

Actins↗

PubMed1992

Nitric oxide alters renal function and guanosine 3',5'-cyclic monophosphate.

Endothelium-derived relaxing factor (EDRF) activates soluble guanylate cyclase, resulting in an increase in vascular smooth muscle guanosine 3',5'-cyclic monophosphate (cGMP) levels, which correlates with its relaxing effect. Using a microdialysis technique, we investigated changes in right and left renal interstitial fluid cGMP levels in response to right intrarenal administration of an EDRF inhibitor, NG-monomethyl-L-arginine (L-NMMA). Studies were conducted in anesthetized dogs (n = 5) in metabolic balance at a sodium intake of 40 meq/day. Urine was collected directly from the right and left ureters individually. Changes in the right and left urinary cGMP excretion and renal function in response to cumulative doses of L-NMMA were studied. In the right kidney, 20-100 micrograms/kg/min L-NMMA caused 1) a dose-dependent decrease in renal interstitial fluid and urinary cGMP levels (p less than 0.0001 and p less than 0.001, respectively), 2) antinatriuresis (p less than 0.01), 3) antidiuresis (p less than 0.01), 4) a decrease in renal blood flow (p less than 0.01) and glomerular filtration rate (p less than 0.01), and 5) a decrease in fractional sodium excretion (p less than 0.01). No changes in left renal interstitial fluid and urinary cGMP levels or excretory and hemodynamic function were observed during right intrarenal administration of L-NMMA at 20 and 60 micrograms/kg/min.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗

PubMed1992

Effects of angiotensin converting enzyme inhibition, sodium depletion, calcium, isoproterenol, and angiotensin II on renin secretion by individual renocortical cells.

Angiotensin-converting enzyme inhibition with enalapril increases the number of glomeruli with juxtaglomerular cells and the number of cells in the afferent arteriole that express the renin gene and contain renin. However, renin release from these newly recruited renin-containing cells has not been demonstrated. Sodium depletion also has been shown to increase renal renin messenger RNA levels. The aim of these studies was to determine whether increases in renin secretion are a result of altered numbers of cells synthesizing/releasing renin or a change in the amount of renin release per cell, or both. Adult Wistar-Kyoto rats were treated with enalapril or sodium depleted and single cell renin secretion of enzymatically dispersed renal cortical cells was examined by reverse hemolytic plaque assay. Enalapril treatment increased the number of renin secreting cells by approximately 10-fold (P < 0.05). The newly recruited renin-secreting cells were not responsive to changes in extracellular calcium concentration or the presence of isoproterenol. At physiological (2.5 mM) extracellular calcium concentration, the amount of renin secreted per cell was approximately 2-fold greater (P < 0.05) when cells from enalapril-treated rats were compared to controls and sodium depletion increased both the number of renin-secreting cells and the amount of renin secreted by approximately 35% (P < 0.05). Angiotensin II (AII) inhibited the number of cells secreting renin in cortical cells prepared from enalapril-treated and control rats. In conclusion, angiotensin converting enzyme inhibition increased renin secretion predominantly by recruitment of additional renin-secreting cells and, to a lesser extent, by augmentation of the amount of renin released per cell. In contrast, sodium depletion increased renin secretion equally by both mechanisms. Newly recruited renin-secreting cells were not regulated by the extracellular calcium concentration or beta-adrenergic stimulation. Angiotensin II inhibited renin secretion directly by decreasing the number of individual cells releasing renin through a process which was independent of the extracellular calcium concentration.

Angiotensin II↗

PubMed1992

The renal dopamine receptors.

Dopamine is an endogenous catecholamine that modulates many functions including behavior, movement, nerve conduction, hormone synthesis and release, blood pressure, and ion fluxes. Dopamine receptors in the brain have been classically divided into D1 and D2 subtypes, based on pharmacological data. However, molecular biology techniques have identified many more dopamine receptor subtypes. Several of the receptors cloned from the brain correspond to the classically described D1 and D2 receptors. Several D1 receptor subtypes have been cloned (D1A, D1B, and D5) and are each coupled to the stimulation of adenylyl cyclase. The D2 receptor has two isoforms, a shorter form, composed of 415 amino acids, is termed the D2short receptor. The long form, called the D2long receptor, is composed of 444 amino acids; both are coupled to the inhibition of adenylyl cyclase. The D3 and D4 receptors are closely related to, but clearly distinct from, the D2 receptor. They have not yet been linked to adenylyl cyclase activity. Outside of the central nervous system, the peripheral dopamine receptors have been classified into the DA1 and DA2 subtypes, on the basis of synaptic localization. The pharmacological properties of DA1 receptors roughly approximate those of D1 and D5 receptors, whereas those of DA2 receptors approximate those of D2 receptors. A renal dopamine receptor with some pharmacological features of the D2 receptor but not linked to adenylyl cyclase has been described in the renal cortex and inner medulla. In the inner medulla, this D2-like receptor, termed DA2k, is linked to stimulation of prostaglandin E2 production, apparently due to stimulation of phospholipase A2. Of the cloned dopamine receptors, only the mRNA of the D3 receptor has been reported in the kidney. The DA1 receptor in the kidney is associated with renal vasodilation and an increase in electrolyte excretion. The DA1-related vasodilation and inhibition of electrolyte transport is mediated by cAMP. The role of renal DA2 receptors remains to be clarified. Although DA1 and DA2 receptors may act in concert to decrease transport in the renal proximal convoluted tubule, the overall function of DA2 receptors may be actually the opposite of those noted for DA1 receptors. Dopamine has been postulated to act as an intrarenal natriuretic hormone. Moreover, an aberrant renal dopaminergic system may play a role in the pathogenesis of some forms of hypertension. A decreased renal production of dopamine and/or a defective transduction of the dopamine signal is/are present in some animal models of experimental hypertension as well as in some forms of human essential hypertension.

Humans↗

PubMed1992

Combined acute hypoxemia and hypercapnic acidosis increases atrial natriuretic polypeptide in conscious dogs.

To evaluate the changes in atrial natriuretic polypeptide during acute hypoxemia and acute hypercapnic acidosis, conscious mongrel dogs with controlled sodium intake were evaluated in four protocols: (1) 80 min of acute hypoxemia (PaO2 = 34 +/- 1 mm Hg) followed by 40 min of combined hypoxemia and hypercapnic acidosis (PaO2 = 38 +/- 1 mm Hg, PaCO2 = 60 +/- 3 mm Hg, pH = 7.15 +/- 0.03) (n = 7); (2) 40 min of combined acute hypoxemia and hypercapnic acidosis (PaO2 = 36 +/- 1 mm Hg, PaCO2 = 56 +/- 2 mm Hg, pH = 7.20 +/- 0.03) induced immediately following control measurements (n = 5); (3) 120 min of acute hypercapnic acidosis (PaCO2 = 58 +/- 1 mm Hg, pH = 7.20 +/- 0.01) (n = 5), and (4) 120 min of normoxemia and normocapnia (n = 7). These studies did not observe any association between urinary sodium excretion and circulating atrial natriuretic polypeptide during acute blood gas derangements in conscious dogs. The natriuresis with acute hypoxemia or acute hypercapnic acidosis was unaccompanied by change in plasma atrial natriuretic polypeptide concentrations. Conversely, the rise in circulating atrial natriuretic polypeptide during combined acute hypoxemia and hypercapnic acidosis was not associated with an increase in urinary sodium excretion. These observations do not exclude a role for atrial natriuretic polypeptide in altering sodium excretion during acute blood gas derangements, since the effects of this autacoid on renal sodium excretion may have been offset by other counterregulatory mechanisms of sodium excretion activated during the acute blood gas derangement.

Acidosis↗

PubMed1991

Spatial association of renin-containing cells and nerve fibers in developing rat kidney.

The development of renin-containing cells and nerve fibers was studied in Sprague-Dawley rat kidneys during the last third of gestation and the first 15 days of postnatal life. Kidney tissue sections were stained for nerve fibers or double stained employing an anti-rat renin polyclonal antibody and a monoclonal antibody (TUJ1) directed against a neuron-specific class III beta-tubulin isotype. Renin-containing cells and nerve fibers were detected at 17 days of gestation, in close spatial relationship along the main branches of the renal artery. During fetal life, renin-containing cells and nerve fibers were spatially associated along arcuate and interlobular arteries, renin-containing cells being also present throughout the entire length of afferent arterioles supplying juxtamedullary glomeruli. During postnatal life the distribution of renin-containing cells progressively shifted to a restricted juxtaglomerular position in afferent arterioles. Simultaneously, density and organization of nerve fibers increased with age along the arterial vascular tree. Our results suggest that innervation of renin-containing cells is present in fetal life and follows the centrifugal pattern of renin distribution and nephrovascular development.

Animals↗

PubMed1991

The student-initiated, faculty-assisted system of evaluation of clinical teaching at the University of Virginia.

The University of Virginia School of Medicine has developed a student-initiated, faculty-assisted system to evaluate the faculty who teach the third-year clinical clerkships. All students complete an evaluation at the end of each clerkship, and the fourth-year class and student government compile the results and publish a detailed annual report of the data, offering constructive criticism and recommendations for change. Teaching faculty then review the report and respond to the student government, the faculty clerkship committee, and the student curriculum committee, addressing the contents of the report and initiating proposals to correct deficiencies and improve teaching. The experience of the first two administrations of this system (1988-1990) has been encouraging, and the authors suggest that the system will be applicable to the evaluation of clinical teaching on a universal basis.

Clinical Clerkship↗

PubMed1991

Inhibition of ANP clearance receptors and endopeptidase 24.11 in maturing rats.

Systemic clearance of atrial natriuretic peptide (ANP) decreases during postnatal development. To determine the relative contribution of ANP clearance (C) receptors and neutral endopeptidase 24.11 (NEP; EC 3.4.24.11) in regulation of plasma ANP concentration ([ANP]) during maturation, 18- to 60-day-old male Sprague-Dawley rats were anesthetized and infused with rat ANP (35 ng.kg-1.min-1). Infusion of the NEP inhibitor phosphoramidon increased [ANP] and urine guanosine 3',5'-cyclic monophosphate (cGMP) excretion in both weanling and adult rats. Infusion of C-ANP, an analogue that binds C receptors selectively, resulted in a greater rise in [ANP] in preweaned than in adult rats, suggesting a maturational decrease in function of C receptors. Despite the increase in [ANP], however, urine flow, cGMP, and sodium excretion failed to increase in preweaned compared with adult rats. Combined infusion of phosphoramidon and C-ANP resulted in a marked increase in [ANP] and cGMP excretion in weanling and adult rats. These results indicate that both C receptors and NEP modulate plasma [ANP] in the physiological range and that each pathway compensates when the other is inhibited. Age-related differences in the renal response to ANP clearance inhibitors may have important physiological implications in the regulation of sodium balance during development.

Animals↗

PubMed1991

Role of intrarenal angiotensin II and alpha-adrenoceptors in renal vasoconstriction with acute hypoxemia and hypercapnic acidosis in conscious dogs.

To evaluate our previous observation of renal vasoconstriction during combined acute hypoxemia and hypercapnic acidosis preceded by acute hypoxemia, we studied 13 conscious mongrel uninephrectomized dogs with chronic renal catheters and controlled sodium intake (80 meq/day for 4 days). Five dogs were studied during combined acute hypoxemia (PaO2, 37 +/- 1 mm Hg) and hypercapnic acidosis (PaCO2, 59 +/- 1 mm Hg; pH 7.20 +/- 0.01). Each dog was studied during infusion of 1) the intrarenal vehicle (n = 5), 2) the intrarenal alpha 1-antagonist prazosin (0.2 micrograms.kg-1.min-1, n = 5), 3) intrarenal [Sar1,Ala8]angiotensin II (70 ng.kg-1.min-1, n = 5), and 4) intrarenal prazosin and [Sar1,Ala8]angiotensin II (n = 4). Immediate induction of combined hypoxemia and hypercapnic acidosis after control measurements during intrarenal vehicle infusion resulted in a decrease in effective renal plasma flow and glomerular filtration rate, increase in renal vascular resistance, and decrease in filtered sodium load in the first 20 minutes of the blood gas derangement. Intrarenal administration of [Sar1,Ala8]angiotensin II failed to reverse the effects of the combined blood gas derangement on renal function. In contrast, intrarenal prazosin administration either alone or in combination with [Sar1,Ala8]angiotensin II abrogated the increase in renal vascular resistance, decrease in glomerular filtration rate, and fall in filtered sodium load. These studies identify a major role for alpha 1-adrenoceptors in the renal vasoconstriction during combined hypoxemia and hypercapnic acidosis.

Acidosis↗

PubMed1991

Renal nerves modulate renin gene expression in the developing rat kidney with ureteral obstruction.

Chronic unilateral ureteral obstruction (UUO) in newborn rats activates renin gene expression in the obstructed kidney, and increases renin distribution along afferent glomerular arterioles in both kidneys. To investigate the role of the renal nerves in this response, 2-d-old Sprague-Dawley rats were subjected to UUO or sham operation. Chemical sympathectomy was performed by injection of guanethidine, whereas, control groups received saline vehicle. At 4-5 wk, renal renin distribution was determined by immunocytochemistry, and renin mRNA levels were determined by Northern blot hybridization. Compared to the saline-treated rats with UUO, renin remained localized to the juxtaglomerular region in both kidneys of rats with UUO receiving guanethidine (P less than 0.05). Moreover, renin mRNA levels were eightfold lower in obstructed kidneys of rats receiving guanethidine than in those receiving saline. Additional groups of rats with UUO were subjected to unilateral mechanical renal denervation: renin gene expression in the obstructed kidney was suppressed by ipsilateral but not by contralateral renal denervation. These findings indicate that either chemical or mechanical denervation suppressed the increase in renin gene expression of the neonatal kidney with ipsilateral UUO. We conclude that the renal sympathetic nerves modulate renin gene expression in the developing kidney with chronic UUO.

Animals↗

PubMed1979

Identification and differentiation of surgically correctable hypertension due to primary aldosteronism.

During a protocol study for the evaluation of patients with primary aldosteronism, a variety of diagnostic studies were employed in an attempt to identify patients with primary aldosteronism and to differentiate patients with adrenal adenoma from patients with idiopathic adrenal hyperplasia. In this study, we are able to demonstrate the utility of (1) absent postural increase in plasma aldosterone concentration, (2) adrenal scanning and (3) normalization of blood pressure with spironolactone therapy in identifying patients with primary aldosterone excess who have an adrenal adenoma, surgical removal of which results in eliminating their hypertension.

Adenoma↗

PubMed1979

Activity of [des-aspartyl1]-angiotensin II in primary aldosteronism.

This study describes the effects of [des-Aspartyl(1)]-angiotensin II ([des-Asp]-AII) on blood pressure and aldosterone production in patients with primary aldosteronism due to aldosterone-producing adrenal adenoma (APA) and idiopathic adrenal hyperplasia (IHA), and in normotensive control subjects. 10 patients with primary aldosteronism, 7 with APA and 3 with IHA, and 6 normotensive control subjects were placed on a constant 150-meq sodium diet for 4 days. [des-Asp]-AII was infused for 30 min at 6, 12, and 18 pmol/kg per min. Three groups of patients were identified on the basis of aldosterone response to [des-Asp]-AII. Group I, composed of normotensive control subjects, showed incremental increases in plasma aldosterone concentration from 6+/-1 to 14+/-3 ng/100 ml (P < 0.01) with [des-Asp]-AII infusion. Group II, composed of patients with primary aldosteronism, showed incremental increases in plasma aldosterone concentration from 33+/-8 to 65+/-13 ng/100 ml (P < 0.05) with 12 pmol/kg per min of [des-Asp]-AII. Group III, also composed of patients with primary aldosteronism, showed no increase of plasma aldosterone concentration with [des-Asp]-AII. Groups I and II showed similar percentage increases in plasma aldosterone concentration (P = NS). Group III showed significantly lower aldosterone responses than group I (P < 0.01). Group II included all patients with IHA and two patients with APA. Group III included only patients with APA. The blood pressure responses to [des-Asp]-AII of subjects in group I did not differ significantly from those of groups II or III.Thus, patients with IHA and a subgroup of patients with APA showed responsiveness to [des-Asp]-AII which was limited to adrenal cortical stimulation of aldosterone biosynthesis. This suggests that adrenal responsiveness to angiotensin is a major control mechanism in some forms of primary aldosteronism. The differential adrenal responsiveness to [des-Asp]-AII in patients with APA indicates either that there are two distinct subpopulations of APA, or that alteration in tumor response to angiotensin occurs during the natural progression of the disease history.

Adrenal Glands↗

PubMed1979

Effects of metoclopramide and bromocriptine on the renin-angiotensin-aldosterone system in man. Dopaminergic control of aldosterone.

This study was designed to investigate the possible role of dopaminergic mechanisms in the control of the renin-angiotensin-aldosterone system in normal man. Six normal male subjects in metabolic balance at 150 meq sodium, 60 meq potassium constant intake received the specific dopamine antagonist, metoclopramide, 10 mg i.v. or placebo followed by angiotensin II infusion 1 h later on 2 consecutive days. Metoclopramide increased plasma aldosterone concentration from 8.2+/-2.2 to 21.0+/-3.3 ng/100 ml (P < 0.005) and plasma prolactin concentration from 18.0+/-4.0 to 91.7+/-4.0 ng/ml (P < 0.001) within 15 min of its administration. At 1 h, plasma aldosterone and prolactin concentrations remained elevated at 16.8+/-2.1 ng/100 ml (P < 0.01) and 86.8+/-15.9 ng/ml (P < 0.005), respectively. Angiotensin II at 2, 4, and 6 pmol/kg per min further increased plasma aldosterone concentration to 27.2+/-3.4, 31.9+/-5.7, and 36.0+/-6.7 ng/100 ml (P < 0.02), respectively. Placebo did not alter plasma aldosterone or prolactin concentrations, but angiotensin II increased plasma aldosterone concentration to 13.7+/-2.4, 19.0+/-1.9, and 23.3+/-3.2 ng/100 ml (P < 0.005). The increment of plasma aldosterone concentration in response to angiotensin II was similar after metoclopramide or placebo. The six subjects also received the dopamine agonist, bromocriptine, 2.5 mg or placebo at 6 p.m., midnight, and 6 a.m. followed by angiotensin II infusion on 2 consecutive d. Bromocriptine suppressed prolactin to <3 ng/ml. After placebo, plasma aldosterone concentration increased from 5.2+/-1.4 to 12.3+/-1.7, 17.2+/-2.2, and 21.8+/-3.5 ng/100 ml (P < 0.01) and after bromocriptine from 7.2+/-1.0 to 14.7+/-3.0, 19.8+/-3.2, and 23.4+/-1.6 ng/100 ml (P < 0.001) with each respective angiotensin II dose. No difference in the response to angiotensin II after bromocriptine or placebo was observed. Plasma renin activity, free 11-hydroxycorticoid concentration, and serum potassium concentration were unchanged by metoclopramide or bromocriptine. The results suggest that aldosterone production is under maximum tonic dopaminergic inhibition which can be overridden with stimulation by angiotensin II in normal man.

11-Hydroxycorticosteroids↗

PubMed1979

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.

Adrenocorticotropic Hormone↗