Biomedical subjects

H Raff

Publications and source records attributed to H Raff.

At least 73 records · Page 4Linked to original sources

PubMed1991

Effect of adrenal hypotension on elicited secretory activity in anesthetized dogs.

The objective of this study was to determine whether three- to fourfold increases in adrenal medullary blood flow (MQ), observed during catecholamine secretion induced by splanchnic nerve stimulation (NS), are necessary for a maximal secretory response. Eight pentobarbital-anesthetized adult male mongrel dogs (25-35 kg) were subjected to two episodes of NS-induced catecholamine secretion. To limit increases in MQ, one NS (20 Hz, 8 V, 1.5 ms) was performed under control conditions, the other was after reduction of adrenal perfusion pressure (PP). PP was 124.8 +/- 6.0 at control and was reduced to 23.0 +/- 1.0 mmHg by inflation of an aortic occluder located 3 in. above the adrenals. NS under control conditions increased ipsilateral MQ (measured using radiolabeled microspheres) from 181 +/- 39 to 1,336 +/- 199 ml.min-1.100 g-1 and adrenal epinephrine secretion from 184 +/- 128 to 11,445 +/- 5,216 ng.min-1.g medulla-1. Contralateral MQ and cortical blood flow were unaffected by NS. Reduction of PP decreased MQ to 32 +/- 6 ml.min-1.100 g-1 and adrenal cortical blood flow from 251 +/- 23 to 25 +/- 6 ml.min-1.100 g-1.PP reduction had no effect on either corticosteroid secretion or unstimulated epinephrine secretion. NS at reduced PP increased ipsilateral MQ to 146 +/- 27 ml.min-1.100 g-1 and epinephrine secretion to 13,935 +/- 5,175 ng.min-1.g medulla-1. These data indicate that epinephrine secretion is not altered when MQ is limited by reduction of PP and suggest that, at normal PP, increases in MQ during catecholamine secretion are not necessary for a maximal secretory response.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenal Cortex Hormones↗

PubMed1991

Lack of coupling between adrenal cortical metabolic activity and blood flow in anesthetized dogs.

To determine whether adrenal O2 consumption and cortical blood flow (CBF) increase during stimulation of cortical secretory activity, exogenous adrenocorticotrophic hormone (ACTH) was infused at 0, 2, and 10 ng.kg-1.min-1 (groups 1, 2, and 3, respectively) into dexamethasone-pretreated, pentobarbital-fentanyl-anesthetized, ventilated dogs. ACTH levels of approximately 20, 100, and 500 pg/ml were obtained in groups 1, 2, and 3, respectively. Cortisol secretion increased after 20 min in groups 2 and 3 (from 0.016 +/- 0.004 to 2.25 +/- 1.36 and from 0.02 +/- 0.01 to 5.32 +/- 1.23 microgram.min-1.g cortex-1, respectively) while adenosine 3',5'-cyclic monophosphate (cAMP) secretion increased after 20 min only in group 3 (from 5.7 +/- 2.8 to 61.3 +/- 18.6 micrograms.min-1.g cortex-1). Whole adrenal gland O2 consumption increased after 20 min in group 3 animals (from 0.89 +/- 0.16 to 1.77 +/- 0.27 ml O2.min-1.100 g tissue-1) but not in the other two groups. CBF measured with radiolabeled microspheres was unaffected by ACTH infusion while O2 extraction increased from a baseline of 5.9 +/- 1.4 to 13.0 +/- 2.4% after 30 min in group 3. These data demonstrate that in anesthetized dogs increases in adrenal cortical secretory activity are associated with increases in O2 consumption, and this increase in O2 consumption is met by increasing O2 extraction, not by increasing cortical blood flow.

Adrenal Cortex↗

PubMed1991

Arginine vasopressin responses to hypoxia and hypercapnia in late-gestation fetal sheep.

The purpose of this study was to determine the interaction of hypoxia and hypercapnia in the control of arginine vasopressin (AVP) secretion in fetal sheep and to determine the role of the peripheral arterial chemoreceptors in that response. We measured the plasma AVP response to hypercapnia and/or hypoxia in catheterized intact or sinoaortic-denervated fetal sheep between 123 and 144 days of gestation. Ewes were exposed to the following inspired gases: two successive 30-min periods of normocapnic normoxia, 30 min of normocapnic normoxia followed by 30 min of normocapnic hypoxia, two successive 30-min periods of hypercapnic normoxia, or 30 min of hypercapnic normoxia followed by 30 min of hypercapnic hypoxia (i.e., asphyxia). Hypercapnia per se had no significant effect on fetal plasma AVP. Normocapnic hypoxia per se resulted in a significant increase in fetal plasma AVP. Although hypercapnia resulted in a significant acidemia, the decrease in arterial pH was more marked under hypoxic conditions. Hypercapnia/acidemia augmented the AVP response to hypoxia. Fetal sinoaortic denervation did not significantly attenuate any of the AVP responses. We conclude that hypercapnia augments the fetal AVP response to hypoxia and that the AVP response to neither normocapnic nor hypercapnic hypoxia is dependent on afferent information carried in the carotid sinus or aortic nerves.

Animals↗

PubMed1991

Influence of angiotensin II on pressure natriuresis and renal hemodynamics in volume-expanded rats.

This study examined whether angiotensin II (ANG II) influences the pressure-natriuretic (PN) response by altering renal cortical or medullary hemodynamics. Studies were performed in Inactin-anesthetized rats that were acutely volume expanded to maintain plasma renin activity and ANG II levels in the physiological range. Neural influences on the kidney were eliminated by renal denervation, and plasma levels of norepinephrine, vasopressin, cortisol, and aldosterone were fixed by intravenous infusion. In control rats (n = 8), sodium excretion increased from 3 to 17 microeq.min-1.g kidney wt-1 as renal perfusion pressure (RPP) was elevated from 96 to 141 mmHg (n = 8). Captopril (2 mg/kg, n = 9) reduced plasma levels of ANG II from 48 +/- 5 to 18 +/- 2 pg/ml, but it did not alter the PN relationship. Infusion of ANG II (20 ng.kg-1.min-1, n = 9) increased plasma levels of ANG II to 232 +/- 42 pg/ml and shifted the PN relationship to the right by 14 mmHg. Captopril increased renal blood flow, and infusion of ANG II returned it to control. Captopril had no effect on glomerular filtration rate (GFR) or glomerular capillary pressure (Pglom); however, subsequent ANG II infusion decreased Pglom from 56 +/- 2 to 48 +/- 2 mmHg and reduced GFR by 30%. Neither captopril nor ANG II altered papillary bloodflow or vasa recta capillary pressure at normal levels of RPP. These results indicate that the shift of the PN relationship during infusion of ANG II is due to a decrease in filtered load and enhanced tubular reabsorption of sodium. Acute blockade of the renin-angiotensin system had little effect on the PN response in volume-expanded rats despite affecting renal hemodynamics, because either the plasma and/or intrarenal levels of ANG II were already suppressed below those needed to influence tubular function or volume expansion inhibits tubular reabsorption in the nephron segments normally influenced by ANG II.

Aldosterone↗

PubMed1991

ACTH and vasopressin responses to insulin-induced hypoglycemia in intact and neurohypophysectomized conscious dogs.

Factors from the neurohypophysis are important in the control of anterior pituitary function. This study evaluated the hypothesis that the neurophypophysis is an integral component of the adrenocorticotropin (ACTH) response to certain stimuli. Furthermore, we investigated the possibility that the importance of the neurohypophysis during corticotropic stimuli can be classified by the magnitude of the systemic vasopressin response induced. The ACTH response to insulin-induced hypoglycemia (INS), nitroprusside hypotension (NP), or ovine corticotropin-releasing factor (CRF) infusion (20 ng/kg/min) was measured in dogs before (intact) and greater than 2 weeks after selective transbuccal neurohypophysectomy (NHX). INS (0.2 U/kg) resulted in a significant decrease in plasma glucose from 93 +/- 1 to 33 +/- 2 mg/dl at 30 min and a significant increase in plasma ACTH from 53 +/- 10 to 306 +/- 33 pg/ml in intact dogs whereas the vasopressin (AVP) response was small (2.8 +/- 0.3 to 5.5 +/- 0.7 pg/ml). NHX had no effect on the blood glucose or ACTH response to INS. NP resulted in large increases in ACTH from 54 +/- 8 to 351 +/- 89 pg/ml and in AVP from 2.7 +/- 0.2 to 272 +/- 98 pg/ml. In contrast to INS, NHX significantly attenuated the ACTH and AVP responses to NP. The ACTH response to CRF was not attenuated by NHX, indicating normal pituitary corticotropic function. In summary, NHX attenuated the ACTH response to hypotension (large peripheral AVP response) but not to INS or CRF (small peripheral AVP response).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1991

Routine inferior petrosal sinus sampling in the differential diagnosis of adrenocorticotropin (ACTH)-dependent Cushing's syndrome: early recognition of the occult ectopic ACTH syndrome.

The clinical, biochemical, and radiographic features of ectopic ACTH-dependent Cushing's syndrome are often indistinguishable from those of pituitary ACTH-dependent hypercortisolism (Cushing's disease). We prospectively evaluated 29 patients with ACTH-dependent hypercortisolism by means of bilateral inferior petrosal sinus ACTH sampling with ovine CRH (oCRH) stimulation. Patients with Cushing's disease (n = 20), had a maximal basal inferior petrosal sinus to peripheral ACTH ratio (IPS:P-ACTH) of 11.7 +/- 4.4 (+/- SE) from the dominant IPS, which increased to 50.8 +/- 18.3 after oCRH administration. Bilateral IPS sampling was necessary to correctly identify patients with Cushing's disease, since the maximal basal nondominant IPS:P-ACTH was less than 2.0 in over 50% of the patients and remained less than 2.0 after oCRH administration in one third. In contrast, patients with occult ectopic ACTH-secreting neoplasms (n = 9) had maximal basal IPS:P-ACTH of 1.2 +/- 0.1 that did not change after oCRH administration. Occult ectopic ACTH-secreting neoplasms were found in 7 of 9 patients from 0.4-14 yr after the recognition of Cushing's syndrome, and 4 of these patients had intermittent hypercortisolism with prolonged periods of remission. Selective endobronchial lavage for ACTH correctly localized a radiologically occult ACTH-secreting bronchial carcinoid in 1 patient, and magnetic resonance imaging identified a similar neoplasm in a patient with a normal chest computed tomographic scan. Basal ACTH and urinary free cortisol excretion were significantly higher in patients with ectopic ACTH than in those with Cushing's disease, but overlap existed between groups. High dose dexamethasone suppression testing inaccurately classified 24% of patients, and radiological imaging of the pituitary and adrenal glands was misleading. The occult ectopic ACTH syndrome is a common form of ACTH-dependent hypercortisolism that cannot be distinguished from Cushing's disease with routine clinical studies. The accurate differential diagnosis of ACTH-dependent Cushing's syndrome requires bilateral inferior petrosal sinus ACTH sampling with oCRH stimulation.

Adrenocortical Hyperfunction↗

PubMed1991

Oxygen sensitivity of potassium- and angiotensin II-stimulated aldosterone release by bovine adrenal cells.

Angiotensin II (AII) and extracellular K+, acting through different intracellular mechanisms, stimulate aldosterone release in a synergistic fashion. We have previously shown that decreases in oxygen (O2) within the physiological range inhibit AII, cyclic AMP (cAMP) and ACTH-stimulated aldosterone release. The present experiment evaluated the effect of various concentrations of O2 on K+-stimulated aldosterone release in the presence and absence of AII. Dispersed bovine adrenal glomerulosa cells were incubated with different concentrations of K+ (0.9-5.4 mmol/l) without and with AII (10 nmol/l) under different concentrations of O2 (0, 5 or 50%); 21% O2 (pO2 = 19.9 +/- 0.5 kPa,n = 9) was used as reference control for comparison. In all cases, increases in K+ stimulated aldosterone release, an effect augmented by AII. Under 0% O2 (pO2 = 8.1 +/- 0.3 kPa, n = 3) and 5% O2 (pO2 = 12.8 +/- 0.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly inhibited compared with that under 21% O2. Conversely, under 50% O2 (pO2 = 36.3 +/- 2.5 kPa, n = 3), aldosterone release stimulated by K+ or K+/AII was significantly augmented. Cortisol secretion was not significantly affected by 5% or 50% O2 but was significantly decreased under 0% O2. The effect of O2 on K+/AII stimulation of aldosterone release, as well as previous experiments with cAMP, progesterone and ACTH, suggest a final common post-receptor oxygen-sensitive component of the aldosterone synthetic pathway. It is suggested that one or more enzymes in the aldosterone synthetic pathway is/are exquisitely sensitive to small changes in O2 within the physiological range.

Adrenal Glands↗

PubMed1990

Stimulation of atrial natriuretic peptide and vasopressin during retrograde mitral valvuloplasty.

Acute mitral obstruction may lead to an increase in atrial natriuretic peptide (ANP) due to increased atrial pressure and a large increase in arginine vasopressin (AVP) due to simultaneous arterial and ventricular baroreceptor unloading. We measured ANP and AVP concentration after transseptal puncture and during percutaneous retrograde mitral balloon valvuloplasty (PRMV) in 11 patients (mean age 57 +/- 12 years; nine women) with mitral stenosis and congestive heart failure. Atrial septal puncture per se resulted in a significant increase in ANP and AVP without a significant change in aortic pressure. Subsequent PRMV led to a further increase in ANP, a transient decrease in aortic pressure from 89 +/- 7 to 45 +/- 4 mm Hg, and a large (fivefold) increase in AVP. ANP and AVP were no longer different from baseline values 18 to 24 after the procedure. This study suggests that transseptal puncture and acute mitral obstruction are major stimuli to ANP release and that combined unloading of arterial and left ventricular mechanoreceptors is a very potent vasopressinergic stimulus.

Aged↗

PubMed1990

Impact of exercise training on plasma adrenocorticotropin response to a well-learned vigilance task.

Plasma adrenocorticotropin hormone (ACTH), cortisol, heart rate, self-reported state anxiety and total reaction time responses in physically active (n = 8) and sedentary (n = 11) middle-aged men were compared during performance of a well-learned, psychologically challenging task. The groups were similar in age (active: 39.9 +/- 8.4 yr vs. sedentary: 44.4 +/- 7.2 yr) and trait anxiety (29.4 +/- 5.2 vs. 34.5 +/- 12.6), but they had different maximal oxygen consumption relative to lean body weight (68.6 +/- 7.1 vs. 44.7 +/- 4.6 ml.kg(-1).min(-1)). During performance of the psychological protocol, the total group had significant increases in heart rate and state anxiety, whereas both ACTH and cortisol remained near baseline levels. ACTH and cortisol were not different between the groups. The sedentary group exercise trained for 4 mo, which resulted in an 18% improvement in maximal aerobic capacity (vO2 max). Exercise intervention did not significantly alter the neuroendocrine response compared to pre-training values or compared to a corresponding control group. These findings suggest that enhanced cardiovascular fitness resulting from exercise training does not affect anterior pituitary-adrenocortical activity during performance of a practiced vigilance task.

Adrenocorticotropic Hormone↗

PubMed1990

Aldosterone control in critically ill patients: ACTH, metoclopramide, and atrial natriuretic peptide.

A subset of critically ill patients has been described with low plasma aldosterone (Aldo) despite elevated plasma renin activity (PRA). In order to investigate possible mechanisms for these findings, the present study evaluated the Aldo response to exogenous ACTH or metoclopramide (MCP) in normal subjects and in patients admitted to the medical ICU. In addition, measurements of clinical status (Acute Physiology and Chronic Health Evaluation [APACHE II]) and atrial natriuretic peptide (ANP) were correlated with adrenal status. Critically ill patients were subdivided into normal (greater than 2) and subnormal (less than 2) Aldo-to-PRA ratio (Aldo/PRA). Patients with basal Aldo less than 70 ng/dl exhibited subnormal Aldo responses to ACTH, regardless of basal Aldo/PRA. However, normal responses to MCP were noted regardless of basal Aldo/PRA. No correlation between Aldo/PRA and APACHE II score or ANP levels was found. We conclude that critically ill patients with dissociated Aldo and renin can generate a normal Aldo response to MCP. This suggests that this syndrome is due to functional and potentially reversible dysfunction of the zona glomerulosa of the adrenal cortex.

Adrenocorticotropic Hormone↗

PubMed1990

Changes in adrenal oxygen consumption during catecholamine secretion in anesthetized dogs.

Prior attempts to study adrenal medullary O2 metabolism during catecholamine secretion have been unsuccessful because venous blood from medulla mixes with venous blood from the much larger cortex. To circumvent this problem, eight adult mongrel dogs were pretreated for 5-6 wk with the adrenocorticolytic agent 1,1-dichloro-2-(o-chlorophenyl)-2-(p-chlorophenyl)ethane (o,p'-DDD). Prednisolone (5 mg/day) and fludrocortisone (0.1 mg.10 kg-1.day-1) were administered orally to prevent adrenocortical insufficiency. Animals were then anesthetized with pentobarbital sodium and subjected to splanchnic nerve stimulation (NS) at 20 and 4 Hz to elicit catecholamine secretion. NS at 20 Hz increased epinephrine secretion from 1.6 +/- 0.7 to 1,780 +/- 762 ng.min-1.g medulla-1 but had no effect on medullary O2 consumption. Medullary blood flow (MQ) increased from 216 +/- 63 to 1,522 +/- 182 ml.min-1.100 g-1, and O2 extraction decreased from 2.7 +/- 0.7 to 0.8 +/- 0.2%. NS at 4 Hz increased epinephrine secretion from 3.1 +/- 1.4 to 76 +/- 17 ng.min-1.g medulla-1 and MQ from 226 +/- 66 to 649 +/- 122 ml.min-1.100 g-1 but had no effect on adrenal O2 consumption or extraction. Cortical blood flow was 342 +/- 98 ml.min-1.100 g-1 at baseline and was unaffected by NS. Gross weight of cortex was reduced by 80% in o,p'-DDD-treated animals, and histological examination of glands from three animals showed only rare islands of glomerulosa cells remaining. These data suggest that increases in MQ during NS do not occur in response to changes in O2 consumption.

Adrenal Glands↗

PubMed1990

Cortisol inhibition of vasopressin and ACTH responses to arterial hypotension in conscious dogs.

We evaluated the role of cortisol as a feedback inhibitor of the vasopressin response to arterial hypotension. Conscious dogs (n = 5) were each studied on 10 different days. There were five different pretreatments: 1) isotonic saline (control), 2) 5.5 or 3) 11 nmol cortisol.kg-1.min-1 iv for 30 min, 4) 6.8 pmol ACTH-(1-24).kg-1.min-1 iv for 30 min, or 5) 1.5 mg dexamethasone im given the night before experimentation. These pretreatments were followed by a stimulus period (30 min) during which mean arterial pressure was decreased a moderate (-19 +/- 1 mmHg) or severe (-29 +/- 1 mmHg) degree with a controlled infusion of intravenous sodium nitroprusside. The vasopressin response to moderate hypotension was not consistently inhibited by any of the pretreatments. In contrast, the large vasopressin response to severe hypotension in the control experiments (from 3.1 +/- 0.3 to 270 +/- 113 pg/ml) was significantly attenuated by cortisol infusion in a dose-dependent manner. Adrenocorticotropin infusion was more effective than dexamethasone as an inhibitor of the vasopressin response to severe hypotension. The data suggest that physiological increases in cortisol inhibit the large increase in vasopressin in response to severe arterial hypotension.

Adrenocorticotropic Hormone↗

PubMed1990

Renin response to hemorrhage in conscious rats: effect of acute reductions in hematocrit.

This study examined the effect of prior exchange transfusion and acute reduction in hematocrit on the subsequent plasma renin concentration (PRC) response to 15 ml/kg hemorrhage in conscious cannulated rats. Long-Evans rats (400-500 g) were assigned to one of eight groups (6-8 rats/group). Rats were exchanged transfused (5 ml total) with whole blood, red blood cells and saline, plasma, or isotonic saline, with the two latter groups showing a decrease in hematocrit of 10-20%. Thirty minutes after exchange transfusion, rats were either subjected to a 0- (control) or 15-ml/kg hemorrhage. Control rats showed no change in mean arterial pressure or PRC regardless of exchange transfusion. The rats exchange transfused with saline had a significant decrease in arterial pH and a more profound hypotension after hemorrhage. PRC ranged from 7 +/- 1 to 11 +/- 1 ng.ml-1.h-1 after exchange transfusion. Subsequent hemorrhage resulted in an increase in PRC that was significantly greater in the saline-transfused group (45 +/- 16 ng.ml-1.h-1) 10 min after hemorrhage. We conclude that exchange transfusion with saline leads to an augmented renin response to hemorrhage in part due to a decrease in arterial pH and more severe hypotension.

Animals↗

PubMed1990

Peripheral chemoreceptor control of fetal renin responses to hypoxia and hypercapnia.

The renin response to hypoxia in late gestation fetal sheep has been well characterized. However, the renin response to asphyxia--the combination of hypoxia and hypercapnia--has not been extensively studied. The purpose of this study was to determine 1) the interaction of hypoxia and hypercapnia in the control of renin secretion in late gestation fetal sheep and 2) the role of peripheral arterial chemoreceptors therein. Chronically catheterized fetal sheep (intact or sinoaortic denervated) were exposed to hypoxia and/or hypercapnia for 30 minutes. Hypercapnia alone had no effect on plasma renin activity or aldosterone but did result in a significant increase in angiotensin II. Hypercapnia combined with hypoxia resulted in a significant increase in renin activity, angiotensin II, and aldosterone. Sinoaortic denervation attenuated the renin and angiotensin II responses to hypercapnia plus hypoxia. The increase in renin and angiotensin II in response to hypercapnia with or without concomitant hypoxia strongly correlated with the magnitude of the decrease in arterial pH in intact fetuses only. Hypoxia alone and in concert with hypercapnia increased mean arterial pressure and decreased heart rate in intact but not sinoaortic denervated fetuses. We conclude that 1) hypercapnia more potently increases plasma renin activity than does hypoxia in late gestation fetal sheep, 2) arterial pH may be the relevant signal perceived by the peripheral arterial chemoreceptors for the control of the renin-angiotensin system during asphyxia, and 3) the cardiovascular response to hypoxia is mediated, in part, by peripheral arterial chemoreceptors.

Aldosterone↗

PubMed1990

The effect of oxygen on aldosterone release from bovine adrenocortical cells in vitro: PO2 versus steroidogenesis.

Hypoxia decreases plasma aldosterone in vivo without a decrease in PRA, angiotensin II (ANG II), ACTH, or cortisol. The present study evaluated whether this could be due to a direct, specific inhibitory effect on the zona glomerulosa related to the magnitude of the decrease in oxygen (O2). Bovine adrenocortical cells were dispersed with collagenase and studied in vitro within 48 h. Cells were stimulated for 2 h with ANG II (0.1-1000 nM) or (Bu)2cAMP (0.3-3 mM) under oxygen levels ranging from 0 to 100% O2 (PO2 from 66 +/- 4 to 561 +/- 46 torr) vs. a reference gas mixture (21% O2 PO2 approximately 140 torr). Exposure to 123 +/- 8, 110 +/- 12, 100 +/- 16, and 66 +/- 4 torr led to 27%, 30%, 40% and 70% inhibition, respectively, of 3 nM ANG II-stimulated aldosterone secretion as compared to 140 +/- 16 torr (reference). Exposure to hyperoxia (288 +/- 36 to 561 +/- 46 torr) led to a small (10%) increase in ANG II-stimulated aldosterone secretion which was not statistically significant. The P50 (half-maximal PO2) for aldosteronogenesis was approximately 95 torr. The results for other doses of ANG II and for cAMP were similar. The inhibitory effect of low O2 was reversed by returning the cells to reference conditions (140 +/- 16 torr). Cortisol secretion was not significantly affected by changes in oxygen tension. We conclude that small changes in O2 within the physiological range directly and specifically inhibit aldosteronogenesis in a dose-dependent manner with a P50 of approximately 95 torr. Inhibition of cAMP-stimulated aldosterone secretion suggests a postreceptor site of action. This direct, reversible, and specific effect on the zona glomerulosa of the adrenal cortex may account for the dissociation of renin and aldosterone during hypoxia in vivo.

Adrenal Cortex↗

PubMed1990

Vasopressin responses to hypoxia in conscious rats: interaction with water restriction.

The purpose of this study was to determine the effect of water restriction on the vasopressin response to hypoxia in conscious Long-Evans rats. Rats were prepared with chronic indwelling femoral artery and vein catheters 1 week before experimentation. At 24 h before the first blood sample, the supply of drinking water was maintained ad libitum (water replete) or removed (water deplete). At 24 h, a control blood sample was taken and then normoxia (21% O2) was maintained or hypoxia (10% O2) induced. Additional blood samples were taken at 1, 18 and 24 h. All blood samples (2.5 ml) were simultaneously replaced with donor blood to maintain isovolaemia. Hypoxia led to a very small and transient increase in vasopressin in the water-replete rats. The combination of hypoxia and water restriction led to a greatly augmented vasopressin response at 1 h (60 +/- 16 pmol/l); this response was also not sustained. Additional non-cannulated rats were exposed to 24 h of normoxia or hypoxia with or without water available ad libitum and posterior pituitaries were collected after decapitation for measurement of vasopressin content. Water restriction, hypoxia and water restriction plus hypoxia all led to decreased pituitary vasopressin content. We conclude that the vasopressin response to hypoxia in conscious rats is small and transient, and that concomitant water restriction augments the vasopressin response to acute but not chronic hypoxia.

Animals↗

PubMed1989

Stimulation of atrial natriuretic peptide and vasopressin during percutaneous transluminal aortic valvuloplasty.

The objective of this study was to determine the effects of transient aortic valve occlusion (balloon valvuloplasty) on vasoactive hormones in patients with heart failure. Plasma atrial natriuretic peptide, vasopressin, aldosterone, adrenocorticotropic hormone (ACTH), and plasma renin activity were measured before, immediately after, and 30 minutes and 18 to 24 hours following balloon inflation in 18 patients. Mean right atrial and pulmonary wedge pressures were 6 and 18 mm Hg before inflations, respectively, and were unchanged after balloon inflations (5 and 13 mm Hg, respectively). Systemic systolic/diastolic pressures were 139 +/- 8/65 +/- 4 mm Hg before occlusion, decreased to 47 +/- 5/34 +/- 3 mm Hg during occlusion, and returned to baseline after occlusions. Baseline atrial natriuretic peptide levels were 267 +/- 43 pg/ml and increased to 513 +/- 71 pg/ml after balloon inflations. Vasopressin levels before occlusion were 9.1 +/- 2.2 pg/ml and increased to 21.4 +/- 4.8 pg/ml after balloon inflations. Plasma renin activity was 5.4 +/- 1.4 ng/ml/hr before inflations and was not significantly changed after balloon inflations. No clinically significant changes in plasma sodium, potassium, creatinine, and osmolality were observed after the procedure. Aldosterone increased from 23 +/- 4 to 40 +/- 7 ng/dl 10 minutes after the last inflation. Plasma ACTH measured in seven patients with increased aldosterone was 28 +/- 8 pg/ml before and increased to 295 +/- 157 pg/ml 10 minutes after balloon inflations. The increases in natriuretic peptide and vasopressin were likely due to elevated intracardiac and decreased arterial pressures, respectively; they persisted in spite of no clinically significant changes in filling pressures 12 to 24 hours after the procedure.(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenocorticotropic Hormone↗

PubMed1989

Low oxygen selectively inhibits aldosterone secretion from bovine adrenocortical cells in vitro.

Systemic hypoxia has been reported to inhibit selectively aldosterone secretion in vivo. The mechanism of this inhibition has not been elucidated. We hypothesized that decreased tissue PO2 directly inhibited aldosteronogenesis. To test this hypothesis, we exposed dispersed adrenocortical cells (90% glomerulosa/10% fasciculata) to decreased PO2 in vitro while simultaneously stimulating aldosterone secretion with angiotensin II, N6,2'-O-dibutyryladenosine 3',5'-cyclic monophosphate (dibutyryl cAMP) adrenocorticotropic hormone (ACTH)-(1-24), or progesterone. Decreasing buffer PO2 from approximately 150 to approximately 85 Torr significantly inhibited basal and angiotensin II, cAMP, progesterone, and ACTH-stimulated aldosterone secretion at all doses of secretagogue. Inhibition was largest for angiotensin II (55 +/- 9% inhibition at 1 microM) and cAMP (54 +/- 8% at 3 mM) and lowest for ACTH (24% at 100 nM) and basal aldosterone secretion (31 +/- 7%). This inhibition was reversed by returning the buffer PO2 to 150 Torr. Cortisol secretion was not significantly inhibited by decreased buffer PO2. We conclude that decreased buffer PO2 significantly inhibits aldosterone secretion in vitro, and this inhibition is reversible and specific. Hypoxia-induced inhibition of aldosterone secretion in vivo may be caused, at least in part, by a direct effect of low tissue PO2 within the adrenal cortex.

Adrenal Cortex↗