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Biomedical subjects

E A Espiner

Publications and source records attributed to E A Espiner.

At least 19 recordsLinked to original sources
PubMed1992

The effect of parathyroidectomy on bone mineral density in primary hyperparathyroidism.

Bone mineral density was studied before, and at one year after successful parathyroidectomy in six postmenopausal, three premenopausal females and one male with primary hyperparathyroidism. Dual photon absorptiometry was used to measure bone mineral density at the lumbar spine in all subjects, and at three areas of the hip in eight of the subjects. There was no significant change in bone mineral density at the lumbar spine after one year. Bone mineral density increased 7.4% at the femoral neck from 0.822 (SEM 0.053) g/cm2 to 0.895 (0.04) g/cm2; p less than 0.01, 8.7% at Wards triangle from 0.681 (0.065) g/cm2 to 0.745 (0.07) g/cm2; p less than 0.02. A 5.6% increase at the trochanteric region from 0.785 (0.053) g/cm2 to 0.803 (0.053) g/cm2 was not significant. These results indicate that significant increases occur in bone mineral density at the hip, but not at the lumbar spine at one year after parathyroidectomy in patients with primary hyperparathyroidism.

Adult↗
PubMed1992

Endothelin-induced changes in intracellular calcium concentration in rat vascular smooth muscle cells: effects of extracellular calcium and atrial natriuretic factor.

The purpose of this study was to examine whether different mechanisms might underlie the changes in intracellular calcium concentration ([Ca2+]i) stimulated by high and low concentrations of endothelin, and whether atrial natriuretic factor (ANF) has an inhibitory effect on endothelin-induced [Ca2+]i changes in cultured rat vascular smooth muscle cells (VSMCs). In calcium-replete buffer, cultured monolayers of rat VSMCs superfused with endothelin at a high concentration (10 nM) exhibited a marked transient rise in [Ca2+]i, followed by a sustained elevation, whereas a low concentration of endothelin (0.1 nM) induced a sustained monophasic elevation. When calcium-free buffer was used, 10 nM endothelin induced a transient rise in [Ca2+]i of lesser amplitude, whereas 0.1 nM endothelin did not produce a significant rise. Pretreatment of VSMCs with ANF and cosuperfusion with endothelin failed to inhibit either transient or sustained endothelin-induced changes in [Ca2+]i in calcium-replete buffer.

Animals↗
PubMed1992

Comparison of the effect of renin inhibition and angiotensin-converting enzyme inhibition in ovine heart failure.

The acute hemodynamic and hormonal effects of incremental doses of a specific ovine renin inhibitor (RI: EMD 52 297) and captopril were compared in an ovine model of heart failure. Both RI and captopril inhibited the renin-angiotensin II (ANG II) system, although the decrease in plasma aldosterone (ALDO) was significant only during captopril infusion. Both agents exhibited strong vasodilator properties with similar decreases in mean arterial pressure (MAP, maximum decrease: RI = -20.5 +/- 2.2 mm Hg, p less than 0.001; captopril = -19.8 +/- 1.7 mm Hg, p less than 0.001) and left atrial pressure (LAP, maximum, decrease: RI = -6.8 +/- 1.5 mm Hg, p less than 0.01; captopril = -6.9 +/- 0.4 mm Hg, p less than 0.01) along with a slight increase in cardiac output (CO, maximum increase: RI = 0.54 +/- 0.11 L/min; captopril = 0.79 +/- 0.26 L/min). The slope of the response between MAP and LAP was similar in all animals, indicating that the agents have a similar effect on cardiac preload and afterload. The similar hemodynamic actions of RI and captopril in this model of congestive heart failure suggest that beneficial effects are due to inhibition of ANG II. Thus, orally active renin inhibitors may offer a useful therapeutic alternative when side effects preclude use of angiotensin-converting enzyme (ACE) inhibitors.

Aldosterone↗
PubMed1992

Acute hemodynamic, hormonal, and renal effects of neutral endopeptidase inhibition in ovine heart failure.

The effects of neutral endopeptidase inhibition (NEP-I) were studied in 6 conscious sheep with heart failure (HF) induced by rapid ventricular pacing for 7 days. Measurements were performed 1 h before and for 6 h after intravenous (i.v.) bolus administration of vehicle and SCH 39370 (1.25 and 5 mg/kg) on separate days. After the higher dose, an index of serum NEP activity decreased from 0.83 +/- 0.05 to 0.13 +/- 0.07 nmol/ml/min (p less than 0.001) at 1 h and then returned to control levels at 6 h. Plasma atrial natriuretic peptide (ANP) and cyclic GMP rose from 328 +/- 28 and 20.2 +/- 4.3 to a peak of 570 +/- 65 pmol/L (p less than 0.001) and 28.7 +/- 6.3 nmol/L (p less than 0.05) respectively. Natriuresis and diuresis were significant and left atrial pressure (LAP) decreased from 21.9 +/- 1.1 to 20.1 +/- 0.8 mm Hg (p less than 0.05). Despite high endogenous ANP levels in HF, NEP-I further increases both ANP and its "second messenger." Its natriuretic and hemodynamic effects are consistent with enhanced ANP activity in renal and vascular tissues, suggesting that NEP-I may be useful for treating HF.

Analysis of Variance↗
PubMed1992

Angiotensin II receptor antagonism in ovine heart failure: acute hemodynamic, hormonal, and renal effects.

The hemodynamic, hormonal, and renal effects of angiotensin II-type 1 receptor antagonism (AT1A) have not been documented previously in heart failure (HF) or compared with angiotensin-converting-enzyme inhibition (ACEI). Accordingly, we investigated the acute (2-h) response to losartan (1 and 10 mg/kg iv) or vehicle (N saline) followed by captopril (12.5 mg) on separate days in an ovine model of HF induced by 7 days of rapid ventricular pacing. Losartan induced a significant rise in plasma renin activity (PRA) and plasma angiotensin II levels (P less than 0.01 and P less than 0.001, respectively), in association with a fall in the plasma aldosterone-to-PRA ratio (P less than 0.001) and plasma atrial natriuretic peptide (P less than 0.05). Mean arterial and left atrial pressure both fell significantly after losartan (P less than 0.001), whereas the rise in cardiac output was not sustained. The response to captopril was similar except for plasma angiotensin II, which declined (P less than 0.001). Glomerular filtration and urine sodium excretion were maintained despite a fall in renal perfusion pressure. In conclusion, the vasodilatation and renal effects of AT1A were similar to ACEI. Thus AT1A may be a useful therapeutic alternative to ACEI in HF.

Angiotensin Receptor Antagonists↗
PubMed1992

Effect of inhibition of endopeptidase 24.11 on responses to angiotensin II in human volunteers.

The effects of endopeptidase 24.11 inhibition on angiotensin-induced changes in plasma angiotensin II, aldosterone, and atrial natriuretic factor concentrations and blood pressure were assessed in normal volunteers. Two groups, each consisting of eight normal volunteers, received stepwise infusions of angiotensin II (2, 4, and 8 ng/kg per minute) on day 5 of dose administration with 25 mg every 12 hours (group 1) or 100 mg every 12 hours (group 2) of an oral inhibitor of endopeptidase 24.11 (UK 79300, candoxatril) or placebo in balanced randomized, double-blind, placebo-controlled crossover studies. Both doses of candoxatril significantly enhanced achieved plasma angiotensin II concentrations during infusions (group 1, p < 0.001; group 2, p < 0.01; overall treatment effect for combined data, p < 0.001). This effect was most pronounced at the highest dose of angiotensin II (treatment-time interaction, p < 0.0001 for combined data) and tended to be more marked with the higher dose of candoxatril (treatment-group interaction, p = 0.08). The pressor response to angiotensin II was clearly enhanced by the lower dose of candoxatril; peak systolic and diastolic pressures exceeded placebo values by approximately 10 mm Hg (p < 0.001 and p < 0.05 for systolic and diastolic pressures, respectively). This effect of candoxatril was absent in group 2, which (unlike group 1) had exhibited a modest natriuretic response (sustained cumulative negative sodium balance, -70 +/- 21 mmol; p < 0.01) to the higher dose of inhibitor. Baseline plasma aldosterone concentrations and the incremental aldosterone response to angiotensin II infusions were not significantly altered by low-dose (group 1) candoxatril.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1992

Central C-type natriuretic peptide but not atrial natriuretic factor lowers blood pressure and adrenocortical secretion in normal conscious sheep.

C-type natriuretic peptide (CNP) and its specific receptor (ANPRB) are richly distributed throughout the brain, especially the anterior pituitary and hypothalamus but not in tissue of nonneural origin. These findings suggest that the actions of CNP, unlike atrial natriuretic factor (ANF), are largely confined to the brain where CNP may participate in the central regulation of hemodynamics and salt and water balance. Therefore, we have studied the hemodynamic, renal, and hormonal effects of continuous intracerebroventricular infusions of CNP (5 micrograms/h for 4 h) in a vehicle-controlled study and compared the responses to those of ANF in normal conscious sheep. Hemodynamic and hormonal responses to ANF were not different from control infusions. There was a trend for urinary sodium and potassium excretion to increase throughout the control infusion but not on the ANF day. Water intake during control infusion (358 +/- 160 ml/4 h) was almost 3-fold that ingested during ANF (127 +/- 89 ml/4 h, NS). In contrast, CNP induced a prompt fall in mean arterial pressure (mean decrement 5 mm Hg), arterial pressure remaining below time control values for the remainder of the infusion (P = 0.006). Rises in both heart rate and PRA observed on the control day tended to be attenuated by CNP. Urine electrolyte response to CNP was similar to that observed with ANF. Compared with control infusions, the responses of both plasma aldosterone (P = 0.006) and cortisol (P = 0.043) were significantly different. Following CNP-induced hypotension, plasma cortisol and aldosterone increased abruptly at 30 min after which values fell to control or lower levels until the infusion was terminated. These studies show that intracerebroventricular CNP lowers arterial pressure without increasing heart rate and also suppresses the adrenocortical response, whereas ANF given under the same conditions has no significant effects. These data support the hypothesis that CNP plays an important role in the central regulation of blood pressure and hormones.

Adrenal Cortex↗
PubMed1992

Vasopressin, corticotrophin-releasing factor, and pituitary adrenal responses to acute cold stress in normal humans.

Acute cold stress is a consistent stimulus to ACTH secretion in rats yet inhibits arginine vasopressin (AVP) in both rats and humans. We have studied the interrelationships of AVP, corticotrophin-releasing factor, and atrial natriuretic factor (ANF) in the hypothalamo-pituitary-adrenal response to acute cold stress in normal humans. Six healthy male volunteers deprived of food and fluid for 6 h, and minimally clothed, were studied in the early afternoon. After a 30-min period at 22 C, subjects were exposed to cold stress (4 C for 30 min), followed by a 30-min equilibration period at 22 C. By the end of the period of cold exposure there was a fall in plasma volume of 7.8 +/- 1.4% (mean +/- SEM), a significant increase in both systolic blood pressure (P = 0.0001) and in plasma norepinephrine level (P = 0.0001), but no change in plasma epinephrine or in plasma ANF. Plasma AVP levels fell significantly (P less than 0.01) to reach a nadir at 5-10 min after cold exposure before returning to baseline levels. A significant fall in plasma cortisol levels occurred during the first 15 min of the baseline period and remained stable thereafter. No significant changes in plasma corticotrophin-releasing factor or ACTH occurred. These results suggest that cold inhibition of AVP release, presumably via afferent baroreceptor pathways, may act to reduce the response of the corticotrophs to a potentially noxious stimulus. Inhibition of AVP and/or ACTH during acute cold exposure are not dependent upon an increase in plasma ANF.

Acute Disease↗
PubMed1992

Acute inhibition of endopeptidase 24.11 in essential hypertension: SCH 34826 enhances atrial natriuretic peptide and natriuresis without lowering blood pressure.

The acute renal, endocrine, and hemodynamic effects of the orally active endopeptidase inhibitor SCH 34826 (400 mg every 6 hours for five doses) were investigated in a group of 6 male patients [with established mild to moderate essential hypertension and left ventricular (LV) hypertrophy] in a balanced random-order double-blind, placebo-controlled cross-over study. Plasma atrial natriuretic factor (ANF) concentrations increased (p < 0.05) to fourfold control values after the first dose of inhibitor, but later postdose increments of ANF were less pronounced. Plasma cyclic GMP also increased significantly (p < 0.05). These effects were associated with a transient modest but significant (p < 0.05) increase in sodium excretion (50 mmol sodium in excess of placebo values) that was complete in 24 h. Mean 24-h urinary excretions of cyclic GMP and immunoreactive ANF were also significantly increased by 55 and 86%, respectively. Other urine indexes (including other electrolytes, volume, creatinine, aldosterone, and cortisol) and renal hemodynamics [including glomerular filtration rate (GFR) and effective renal plasma flow (RPF)] were unchanged. Renin-angiotensin-aldosterone system (RAAS) activity was not significantly altered. Plasma epinephrine increased after the initial three doses of SCH 34826. Systolic blood pressure (SBP) and heart rate (HR) were not altered by SCH 34826. Diastolic BP (DBP) increased slightly (p = 0.044). Acute inhibition of endopeptidase 24.11 by SCH 34826 in essential hypertension caused significant increments in plasma ANF and cyclic GMP together with modest natriuresis. No antihypertensive effect was observed in the first 30 h of treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

Atrial Natriuretic Factor↗
PubMed1991

Biological actions of cleaved atrial natriuretic factor (ANF101-105/106-126) in conscious sheep.

Atrial natriuretic factor (ANF) cleaved between Cys105 and Phe106 is the primary metabolite of ANF and circulates in human plasma. Because the role of this metabolite in vivo and its possible interaction with intact ANF are unclear, we studied the biologic effects of a 2-h infusion of rat cleaved ANF101-105/106-126 (15 pmol/kg/min) or vehicle alone in six normal sheep. Infusions of cleaved ANF increased venous plasma levels of cleaved ANF from less than 5 to 260 pmol/L and induced a progressive and significant increase in plasma cyclic GMP (p = 0.025) without significantly affecting plasma ANF levels. These changes were associated with a small (nonsignificant) decrease in arterial pressure and a significant increase in heart rate (HR) and sympathetic nervous activity and were followed by activation of the renin-angiotensin-aldosterone (RAA) axis after infusions were terminated. Unlike ANF itself, cleaved ANF was not natriuretic and did not reduce plasma volume or right atrial pressure. Calculated metabolic clearance rate (MCR) (1.47 +/- 0.4 L/min) and disappearance rate of cleaved ANF from plasma (4.8 +/- 0.37 min) were similar to values reported previously for intact ANF in sheep. These studies show that cleaved ANF stimulates guanylate cyclase and alters hemodynamics and the RAA system in vivo.

Animals↗
PubMed1991

Plasma corticotrophin releasing factor and vasopressin responses to exercise in normal man.

OBJECTIVE: To evaluate the hypothalamo-pituitary-adrenal (HPA) response to both mild and intense exercise. DESIGN: Maximum oxygen consumption (VO2max.) was initially determined. Exercise to 20% (mild) and 90% (intense) VO2max. was undertaken in random order. Subjects were exercised over a 5-minute period to the required level of intensity, which was maintained for a further 10 minutes. SUBJECTS: Six trained male athletes. MEASUREMENTS: Brachial vein blood was sampled before and at 5-minute intervals during and after exercise and assayed for plasma cortisol, ACTH, arginine vasopressin (AVP), corticotrophin releasing factor (CRF), sodium and lactate levels. Haemoglobin and haematocrit were measured before and at the end of exercise. Heart rate was monitored continuously and blood pressure measured whenever blood was sampled before and after exercise. RESULTS: Maximum heart rate was 184 +/- 2 and 82 +/- 5 (mean +/- SEM) beats per minute at 90 and 20% VO2max. respectively. Plasma volume fell by 8.7 +/- 2.4% with intense exercise. Significant increases in plasma concentrations of AVP, ACTH and cortisol, but not CRF, occurred during intense exercise. Plasma sodium concentration, which increased during intense but not mild exercise, peaked at 10 minutes after the onset of exercise and preceded the rise in plasma AVP. The AVP peak clearly preceded the ACTH peak in two subjects and occurred synchronously with it in three subjects. CONCLUSION: These results indicate that although significant HPA activation occurs during intense exercise, CRF does not appear to play a major role in mediating the ACTH response to an acute episode of vigorous exercise in man. AVP may be more important in this regard.

Adrenocorticotropic Hormone↗
PubMed1991

Atrial natriuretic peptide and water and electrolyte transport in the human jejunum.

The effects of atrial natriuretic peptide were investigated on water and electrolyte transport in the human jejunum. Six healthy male volunteers (aged 21-33 years) were studied using a triple lumen perfusion technique. A plasma like electrolyte solution containing polyethylene glycol (5 milligrams) as a non-absorbable marker was perfused into the jejunum at 10 ml/min, and net water and electrolyte transport and transepithelial potential difference were measured. Subjects were studied single blind on two occasions with either intravenous atrial natriuretic peptide (6 pmol/min/kg for 90 minutes) or placebo (saline), both after controlled sodium intake over three days. Plasma atrial natriuretic peptide concentrations rose from (mean (SD)) 10.3 (3.6) pmol/l to a peak of 96.0 (61.8) pmol/l. Jejunal net water and electrolyte fluxes and potential difference were identical in both the atrial natriuretic peptide and the control studies. Compared with placebo atrial natriuretic peptide induced a significantly greater diuresis (peak 10.2 (6.0) v 1.8 (1.0) ml/min, p less than 0.05) and natriuresis (peak 1069 (351) v 376 (208) mumol/min, p less than 0.01) and haemoconcentration (haematocrit 0.405 (0.040) v 0.368 (0.018), p less than 0.01). There was no difference in blood pressure, pulse rate, plasma electrolytes, and plasma osmolality between the two studies. There was no evidence to suggest an effect of atrial natriuretic peptide on jejunal water and electrolyte transport in healthy human subjects.

Adult↗
PubMed1991

Hemodynamic and hormonal effects of neutral endopeptidase inhibitor SCH 39370 in sheep.

Whole body clearance of atrial natriuretic factor is due to both receptor uptake and enzymatic degradation initiated by neutral endopeptidase 24.11. The effects of neutral endopeptidase inhibition have been studied in seven sodium-replete sheep using SCH 39370, a specific and potent inhibitor of neutral endopeptidase, in the presence or absence of exogenous hormone [rat ANF-(101-126), 2.4 pmol/kg/min for 2 hours]. SCH 39370 alone (2.5 mg/kg bolus) increased plasma atrial natriuretic factor and plasma cyclic GMP levels, lowered arterial pressure for periods beyond changes in plasma atrial natriuretic factor or cyclic GMP, and suppressed both plasma aldosterone and cortisol levels when compared with vehicle injections. The effects of SCH 39370 were similar to or exceeded those of atrial natriuretic factor infusions, which induced significantly greater increases in plasma atrial natriuretic factor (p = 0.01). Neither agent alone was natriuretic. When SCH 39370 and atrial natriuretic factor were given together, plasma cyclic GMP but not atrial natriuretic factor levels were increased (p = 0.013) compared with atrial natriuretic factor infusion alone, and the half-life was prolonged (p = 0.002) in the presence of SCH 39370. The hypotensive response was greater than that induced by atrial natriuretic factor alone (p = 0.03) but not different from SCH 39370 alone. Inhibitory effects of SCH 39370 on aldosterone levels were similar in the presence of absence of exogenous atrial natriuretic factor.(ABSTRACT TRUNCATED AT 250 WORDS)

Aldosterone↗
PubMed1991

Intracerebroventricular atrial natriuretic factor (ANF) antiserum inhibits volume-induced ANF in sheep: evidence for the brain's regulation of ANF secretion.

Plasma volume expansion stimulates cardiac secretion of atrial natriuretic factor (ANF) and also increases the ANF concentration in cerebrospinal fluid. In order to determine whether brain ANF is involved in the compensatory response to hypervolemia or the regulation of cardiac secretion of ANF, we have studied the integrated hemodynamic, renal, and hormonal response to acute volume expansion (15 ml/kg Dextran over 30 min) in five sheep given nonimmune serum (control) and ANF antiserum by intracerebroventricular (icv) injections on separate days. Dextran loading caused similar decreases in hematocrit and increases in central venous and mean arterial pressures on both study days. Heart rate was higher after antiserum injections (P less than 0.05). Dextran loading increased plasma ANF on the control (20 pmol/liter maximal mean increment above baseline) but not on the antiserum day (P less than 0.01). The diuresis (P less than 0.01) and natriuresis (P less than 0.05) observed on the control day was inhibited by icv antiserum. Plasma aldosterone and cortisol levels showed similar falls in response to the dextran load on both days. These experiments show that icv ANF antiserum inhibits both the increase in cardiac secretion of ANF and the renal response to plasma volume expansion without affecting hemodynamic status. These data support the hypothesis that the brain ANF system is important in the systemic responses to volume loading.

Aldosterone↗
PubMed1991

EC 24.11 inhibition in man alters clearance of atrial natriuretic peptide.

Metabolic clearance and the biological effects of exogenous human atrial natriuretic factor (ANF) were assessed in two groups each of eight normal volunteers receiving 2-h iv infusions of ANF (2.5 pmol/kg.min) on the fifth day of dosing with the orally active inhibitor of endopeptidase 24.11, candoxatril (25 mg every 12 h in group 1 and 100 mg every 12 h in group 2), and placebo in balanced randomized, double blind, placebo-controlled, cross-over experiments. Although 4 days of pretreatment with the endopeptidase inhibitor did not affect basal plasma ANF, candoxatril enhanced mean ANF-induced increases in plasma ANF by 27 pmol/L (P = NS) and 42 pmol/L (P less than 0.002) in groups 1 and 2, respectively. Calculated MCRs for ANF were significantly reduced by both doses of candoxatril [group 1, 2.5 +/- 0.4 vs. 4.3 +/- 0.6 L/min (P less than 0.01); group 2, 2.3 +/- 0.4 vs. 5.6 +/- 0.8 L/min (P less than 0.001)]. ANF significantly enhanced urinary sodium excretion above preinfusion values in both study phases in both groups. Candoxatril significantly further augmented natriuresis in group 2 (P less than 0.01), but not group 1. Inulin clearance was minimally enhanced, and para-aminohippuran clearance was slightly decreased by candoxatril in both groups. Neither effect alone was statistically significant, but derived renal filtration fractions were significantly enhanced in both groups [group 1, 15.5 +/- 0.5% vs. 13.9 +/- 0.6% (P less than 0.01); group 2, 19.3 +/- 1.9% vs. 18.0 +/- 2.7% (P less than 0.01)]. Basal and stimulated cGMP concentrations in both plasma and urine were significantly enhanced by candoxatril in the two groups (P less than 0.001 and P less than 0.01, respectively, for combined data). Urinary ANF immunoreactivity was significantly enhanced by candoxatril in both groups (P less than 0.05 and P less than 0.01 in groups 1 and 2, respectively), with a more pronounced effect evident at the higher dose (P less than 0.01). These results show that chronic pretreatment with an endopeptidase inhibitor in normal man causes a dose-related reduction in the metabolic clearance of exogenous ANF, amplifies cGMP, and increases renal filtration and the natriuretic responses to infused ANF.

Adult↗
PubMed1991

Prolonged inhibition of endopeptidase 24.11 in normal man: renal, endocrine and haemodynamic effects.

The renal, hormonal and haemodynamic effects of chronic (4 days) dosing with an inhibitor of endopeptidase EC 3.4.24.11 (UK 79300) were assessed in two groups, each of eight normal volunteers, receiving 25 mg every 12 h (group 1) or 100 mg every 12 h (group 2) of UK 79300 in double-blind, balanced-randomized, placebo-controlled, crossover studies. Group 2 (but not group 1) exhibited a significant transient natriuresis (P less than 0.01) and a consequent sustained negative cumulative sodium balance (70 +/- 21 mmol) which was established within 48 h and remained for the duration of dosing with UK 79300. Urine and plasma cyclic guanosine monophosphate (cGMP) levels rose significantly above placebo values (P less than 0.01 and P less than 0.001, respectively) in both groups and the effect was sustained throughout the dosing period. Plasma atrial natriuretic factor (ANF) was slightly enhanced by UK 79300 in group 1 (P less than 0.05) but not significantly increased in group 2. Despite a significant increase in heart rate in both groups (P less than 0.001) and of natriuresis in group 2, there was minimal evidence of renin-aldosterone activation in either group. Trends towards lower systolic pressures, observed in both groups, did not attain statistical significance. These findings suggest chronic treatment with UK 79300 induces an increase in tissue ANF levels, with sustained enhancement of plasma and urine concentrations of ANF second messenger (cGMP) and increased heart rate.

Aldosterone↗
PubMed1990

Arginine vasopressin in Cushing's disease.

Bilateral simultaneous blood samples were taken from the inferior petrosal sinuses of nine patients with Cushing's disease for measurement of adrenocorticotropin (ACTH), vasopressin (AVP), prolactin, growth hormone, luteinising hormone (LH), and follicle stimulating hormone (FSH). Inter-sinus gradients for ACTH (range 3.3-18.2) and AVP (2.0-375) correctly lateralised the microadenoma in seven of these patients. One additional patient showed an increased gradient for AVP but not ACTH on the side of the tumour. The correlation between the AVP and ACTH concentrations in the petrosal sinus draining the microadenoma was significant. Petrosal sinus plasma concentrations of prolactin and growth hormone were also significantly higher on the side of the tumour than on the non-tumour side. Evidence against a non-specific tumour effect on the secretion of all pituitary hormones was the fact that in most cases the gradients for LH and FSH were not significant. It is proposed that increased delivery of AVP to part of the pituitary may result from an aberrant blood supply, and that AVP may interact with corticotropin releasing factor to promote tumour growth and ACTH release.

Adenoma↗