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Biomedical subjects

H Raff

Publications and source records attributed to H Raff.

At least 109 records · Page 6Linked to original sources
PubMed1986

Vasopressin responses to corticotropin releasing factor and hyperosmolality in conscious dogs.

We recently reported that ovine corticotropin releasing factor (CRF) infusion in conscious dogs elevated plasma vasopressin. The present study examines the vasopressin, adrenocorticotropic hormone (ACTH), and cortisol responses to CRF infusion (20 ng X kg-1 X min-1), to hypertonic saline infusion (NaCl 0.054 meq X kg-1 X min-1), and to simultaneous coinfusion of CRF and NaCl (CRF + NaCl) without (no-dex) or with (dex-treated) dexamethasone pretreatment in six conscious dogs (6-8 experiments/dog). CRF had no significant effect on plasma sodium or osmolality, blood pressure, or heart rate. NaCl increased plasma sodium from 146 +/- 1 to 151 +/- 1 meq/l and plasma osmolality from 298 +/- 3 to 305 +/- 3 mosmol/kg. Vasopressin increased significantly during CRF (2.1 +/- 0.5 to 4.8 +/- 1.1 pg/ml) and NaCl (1.9 +/- 0.3 to 5.0 +/- 0.8 pg/ml). Coinfusion of CRF and NaCl resulted in a response larger than the sum of the two infusions alone (3.0 +/- 1.6 to 31.4 +/- 18.5 pg/ml). The ACTH response to CRF (45 +/- 8 to 288 +/- 88 pg/ml) was not augmented by coinfusion with NaCl. DEX attenuated the vasopressin and ACTH responses to each infusion. We conclude that CRF-induced increases in vasopressin are augmented by a simultaneous osmotic stimulus. In addition, the plasma vasopressin responses to CRF and/or hypertonic saline infusion are inhibited by glucocorticoid pretreatment.

Adrenocorticotropic Hormone↗
PubMed1986

Renin-angiotensin II-aldosterone and ACTH-cortisol control during acute hypoxemia and exercise in patients with chronic obstructive pulmonary disease.

Acute hypoxia has been reported to induce a decrease in aldosterone levels despite no change or increases in plasma renin activity and ACTH. Converting enzyme inhibition and/or mild hypokalemia have been suggested as possible mechanisms for this dissociation. We studied 15 patients with chronic obstructive pulmonary disease (COPD) who used continuous ambulatory O2 therapy (home O2). Group A (n = 10) had O2 discontinued for 30 min before exercise to induce hypoxemia; Group B (n = 5) had O2 continued for 30 min (time control). Discontinuation of home O2 in Group A resulted in a significant fall in Pao2 from 77 +/- 6 to 51 +/- 2 torr. Arterial CO2 tension decreased and the pHa increased slightly. Renin, angiotensin II, plasma potassium, and sodium did not change during hypoxemia, whereas ACTH increased significantly. Despite this, aldosterone decreased from 26 +/- 5 to 18 +/- 2 ng/dl. Group B (time control) did not exhibit significant changes in hormones over 30 min, indicating that the effects observed in Group A were specific to O2 discontinuation. Exercise in Group A induced significant increases in ACTH, potassium, and aldosterone. We conclude from these data that acute hypoxemia in patients with COPD results in a decrease in aldosterone not related to converting enzyme inhibition, ACTH, or plasma potassium.

Adolescent↗
PubMed1985

Rate sensitivity of blood pressure to hypoxia.

A biochemical kinetic model is used to describe changes in mean arterial blood pressure in dogs to three different rates of fall of arterial partial pressure of oxygen. The model is a linear loop with one variable rate coefficient (parametric control) which has been previously shown to characterize the rate sensitivity to presented stimuli. A three component model was identified under a least squares criterion and it showed that a unique (stimulation independent) representation can be obtained which can serve as a conceptual framework for the study of this phenomenon.

Animals↗
PubMed1985

Control of ACTH and vasopressin in neurohypophysectomized conscious dogs.

Adrenocorticotropin (ACTH), cortisol, and vasopressin responses to clamped decreases in blood pressure (MAP) and to ovine corticotropin-releasing factor (CRF) infusion (20 ng X kg-1 X min-1) in intact and neurohypophysectomized (NHX) conscious dogs were examined. Mean arterial blood pressure was decreased 28 mmHg by a controlled infusion of sodium nitroprusside. Hypotension induced large increases in ACTH (peak 164 +/- 25 pg/ml), cortisol (peak 12.5 +/- 2.5 micrograms/dl), and vasopressin (peak 221 +/- 64 pg/ml) in intact (n = 7) dogs. NHX (n = 7) significantly attenuated these responses to hypotension. CRF infusion induced increases in ACTH similar in intact (n = 4) and NHX (n = 4) dogs. However, cortisol responses were significantly attenuated by NHX. Interestingly, CRF infusion induced small but significant increases in vasopressin from 3.0 +/- 1.1 to 8.1 +/- 2.0 pg/ml. We conclude that NHX attenuates ACTH and vasopressin responses to hypotension and cortisol responses to CRF-induced increases in ACTH. CRF seems to stimulate vasopressin release.

Adrenocorticotropic Hormone↗
PubMed1985

Acute volume expansion decreases adrenocortical sensitivity to ACTH and angiotensin II.

This study examined the plasma aldosterone and corticosteroid responses to a 60-min infusion of adrenocorticotropin (ACTH) or angiotensin (ANG) II started immediately after an acute isotonic saline volume expansion (0.5 ml . kg-1 . min-1 for 30 min). Five conscious dogs of either sex with exteriorized carotid loops were used in this repeated-design study. Volume expansion per se caused a 10% decrease in hematocrit, a 12.5% decrease in plasma protein, and a 2.7-mmHg increase in central venous pressure with no change in mean arterial pressure, heart rate, or plasma sodium. Volume expansion per se also resulted in significant reductions in vasopressin, plasma renin activity, ACTH, aldosterone, and corticosteroid levels. The aldosterone responses to ACTH and ANG II were significantly inhibited (46-71%) by acute volume expansion. The corticosteroid response to ACTH was 19-29% inhibited by volume expansion. We conclude that acute volume expansion significantly inhibits the adrenocortical sensitivity to its tropic hormones probably via alterations of synergistic factors.

Adrenal Cortex↗
PubMed1984

Renin and ACTH responses to hypercapnia and hypoxia after chronic carotid chemodenervation.

We studied the effect of chronic carotid body denervation on renin (plasma renin activity, PRA), adrenocorticotropin (ACTH), blood pressure, and hematocrit responses to acute normocapnic (arterial CO2 partial pressure, PaCO2, 35 Torr) and hypercapnic (PaCO2, 65 Torr) hypoxia (arterial O2 partial pressure, PaO2, 31 Torr) in five anesthetized, artificially ventilated dogs. Animals were studied at least 3 days before and again at least 10 days after carotid body denervation (bilateral carotid sinus nerve resection). Increases in PRA during hypercapnic normoxia [21.8 +/- 6.4 ng angiotensin I (ANG I) X ml-1 X 3 h-1] and normocapnic hypoxia (13.3 +/- 4.2 ng ANG I X ml-1 X 3 h-1) were not attenuated by carotid body denervation. Increases in ACTH during normocapnic hypoxia (117 +/- 34 pg/ml) were attenuated but not eliminated by carotid body denervation; the increase in ACTH during hypercapnic hypoxia (295 +/- 93 pg/ml) was not attenuated by carotid body denervation. Both the blood pressure and hematocrit responses to normocapnic and hypercapnic hypoxia were attenuated by carotid body denervation. We concluded that 1) the renin response to hypercapnia and hypoxia is not a carotid chemoreflex, 2) the ACTH response to hypoxia is partially a carotid chemoreflex, and 3) blood pressure and hematocrit responses to hypoxia are primarily carotid chemoreflexes.

Adrenal Cortex Hormones↗
PubMed1984

Measurement of hormones and blood gases during hypoxia in conscious cannulated rats.

Simple inexpensive methods are described for implanting chronic arterial cannulas for remote stress-free blood sampling of conscious unrestrained rats and for delivering acute isocapnic hypoxia to these rats in their home cages. The day before experimentation cages were placed in plastic bags with air (21% O2) flowing through at 15 1/min (normoxia). The next morning either normoxia was continued or isocapnic hypoxia (arterial PO2 38 Torr, arterial PCO2 38 Torr) was administered without handling or disturbing the rats. Repeated arterial samples were collected for measurement of blood gases, hematocrit, corticosterone, and ACTH. Blood pressure increased transiently (by 10 mmHg at 10 min) and plasma corticosterone and ACTH levels increased fivefold; hematocrit and heart rate did not change significantly. In rats receiving normoxia, all of these variables remained low. This preparation is useful for studying in conscious rats the regulation of endocrine systems easily stimulated by handling and for studying endocrine and cardiovascular adaptations to environmental stimuli such as hypoxia.

Acid-Base Equilibrium↗
PubMed1984

Responses of in vitro rat diaphragm to changes in acid-base environment.

In vitro rat diaphragms initially demonstrated a decrease in the force of the twitch contraction (FC) in response to field electrode stimulation when exposed to an unbuffered increase in PCO2 (UIPCO2). These diaphragms tended to regain their initial FC upon addition of a beta-agonist even while the increased PCO2 perdured. The effect of the agonist could be reversed by propranolol. Four hemidiaphragms were bathed in a medium containing curare and exposed to UIPCO2. Their tension values were compared to the opposite sides bathed without curare and exposed to UIPCO2 of the same intensity and duration. There was no statistically significant difference in the response. Subsequently 10 rat diaphragms were each systematically challenged by UIPCO2, buffered increases in PCO2 (BIPCO2), unbuffered decreases in bicarbonate (UDHCO3), and buffered decreases in bicarbonate (BDHCO3) first without and then with isoproterenol (10(-6) M). Without isoproterenol all four challenges after 15-min exposure produced a decrease in FC, the least by BIPCO2; the largest, by UDHCO3. Upon addition of isoproterenol, FC actually increased during BIPCO2; the decreases in FC in response to UIPCO2 and UDHCO3 were abolished; the FC in response to BDHCO3 was still decreased, but less severely. The effect of the isoproterenol was not due to its following the four challenges without isoproterenol. The different magnitudes in the FC response and the presumed lack of uniform change in intracellular pH during the four challenges suggest the possibility that different components in the sarcolemma, or in the excitation-contraction coupling mechanisms responsible for the genesis of the FC are affected by the four challenges, but the nerve or neuromuscular junction may also be affected.

Acid-Base Equilibrium↗
PubMed1984

Feedback inhibition of adrenocorticotropin and vasopressin responses to hypoxia by physiological increases in endogenous plasma corticosteroids in dogs.

We examined the influence of increases in plasma corticosteroids produced by ACTH infusion on subsequent ACTH and vasopressin (AVP) responses to hypoxia in anesthetized dogs. Basal and stimulated ACTH levels were inhibited by increases in corticosteroids. Moderate increases in corticosteroids (5.2 micrograms/dl) caused a 50% reduction in the subsequent integrated ACTH response to hypoxia. Maximal increases in corticosteroids eliminated the integrated ACTH response to hypoxia. In addition, AVP responses to hypoxia were attenuated by prior maximal elevations in corticosteroids. Physiological elevation of corticosteroids inhibits subsequent ACTH and AVP responses to hypoxia.

Adrenal Cortex Hormones↗
PubMed1983

T-cell macrophage subset interactions and decreased autologous mixed lymphocyte reaction in Sjögren's syndrome.

T-cell macrophage subset interactions were studied in relation to the decreased autologous mixed lymphocyte reaction (AMLR) in 15 patients with Sjögren's syndrome (SS). Monoclonal antibodies against a macrophage (M theta) subset (Mac-120) stimulatory in the AMLR and against nonpolymorphic determinants of Ia antigen were used to identify adherent M theta. Four patients with decreased AMLR had a reduced percentage of Mac-120+ cells, suggesting that a defect in stimulatory M theta may account for their decreased AMLR. No correlation was found between the magnitude of the AMLR and the percentage of Ia+ M theta. Another six patients with diminished AMLR had a normal to high percentage of Mac-120+ M theta. However, this group of SS patients showed a decreased response to Concanavalin A, suggesting that they may have a defect in the responding T cells. Patients with normal AMLR had normal percentages of Mac-120+ M theta and showed normal responses to T-cell mitogens and alloantigens. These results suggest that a defective AMLR may have multiple causes. SS patients are heterogeneous in this regard and can be sorted into three groups using the AMLR and monoclonal antibodies.

Adult↗
PubMed1983

Vasopressin, ACTH, and corticosteroids during hypercapnia and graded hypoxia in dogs.

We examined the interaction of graded hypoxia and hypercapnia on stimulation of vasopressin (AVP), ACTH, and corticosteroids in nonsurgically stressed, pentobarbital-anesthetized, gallamine-paralyzed ventilated dogs. Partial pressure of O2 in arterial blood (PaO2) levels of approximately 26-29, 38-41, 54-57, and 83-88 Torr were achieved by altering the fractional concentration of O2 in dry inspired gas with a normocapnic (PaCO2, 35 Torr) and hypercapnic (PaCO2, 59 Torr) background. Normocapnic hypoxia produced a PaO2-dependent increase in AVP, ACTH, and corticosteroids. The threshold PaO2 for AVP was lower (approximately 35 Torr) than for ACTH (approximately 45 Torr). AVP, ACTH, and corticosteroids at all PaO2 levels were higher during hypercapnia. In addition, an ACTH and corticosteroid dose-response correlation estimated the threshhold ACTH to be 20-30 pg/ml. The PaO2-dependent hormone increases and the augmentation of these relationships by hypercapnia are consistent with a peripheral chemoreceptor-mediated reflex. In addition, hypoxia and hypercapnia did not seem to alter the high sensitivity of the adrenal cortex for ACTH.

Adrenal Cortex Hormones↗
PubMed1983

Vasopressin, ACTH, and blood pressure during hypoxia induced at different rates.

We decreased arterial PO2 at three different rates and measured blood pressure (BP), vasopressin (AVP), ACTH, and corticosteroid levels in nonsurgically stressed, anesthetized, paralyzed dogs. PaO2 was lowered to 28 Torr in 2 (fast), 10 (moderate), and 20 min (slow). The fast dPO2/dt produced a large spike in BP. Increases in AVP, ACTH, and corticosteroids were similar regardless of the dPO2/dt. When the spike in BP during the fast dPO2/dt was prevented with nitroprusside, hormone levels increased more quickly and were higher during the first 20-30 min of hypoxia. By 60 min, hormone levels were not different between experiments. The data suggest that 1) faster decreases in PO2 produce larger increases in BP, 2) increases in AVP, ACTH, and corticosteroids are primarily sensitive to the level of steady-state PaO2, and 3) increases in BP inhibit stress-induced increases in AVP and ACTH.

Adrenal Cortex Hormones↗
PubMed1983

Effect of hypoxia and hypercapnia on catecholamine content in cat carotid body.

The purpose of this study was to determine the content of catecholamines (CA) in the cat carotid body before and after 0.5 h exposures to normoxic normocapnia [arterial O2 partial pressure (Pao2) 126 +/- 28 Torr, arterial CO2 partial pressure (Paco2) 36.4 +/- 1.5 Torr], hypoxic normocapnia (Pao2 25 +/- 3 Torr, Paco2 36.7 +/- 3.3 Torr), and normoxic hypercapnia (Pao2 132 +/- 13 Torr, Paco2 = 98.2 +/- 7.6 Torr). CA synthesis was blocked using alpha-methylparatyrosine methyl ester (AMPT) prior to alterations in the inspired air. There was a significant decrease in carotid body content of dopamine (DA), norepinephrine (NE), and epinephrine (E) 1 h after AMPT administration. Analysis of variance and Duncan new multiple range procedures revealed that during the subsequent 0.5-h exposures to normoxia, hypoxia, or hypercapnia, only the decrease in DA during hypoxia was significantly greater than that during normoxia; the loss during hypercapnia was not. The decreases in NE during the three exposures were indistinguishable among themselves as were the decreases in E. The decrease in CA content is probably attributable to increased release. The data reveal that the release of CAs during the chemoreception of hypoxia is different from that during the chemoreception of hypercapnia and support the concept of different mechanisms for the chemoreception of hypoxia and hypercapnia.

Animals↗
PubMed1983

Surgery potentiates adrenocortical responses to hypoxia in dogs.

We studied the effect of prior surgery on the ACTH and corticosteroid responses to acute hypoxia. Five conditioned, pentobarbital-anesthetized, gallamine-paralyzed mongrel dogs were exposed to 24 min of isocapnic hypoxia (11% O2/89% N2) 2 hr (Expt I) and approximately 1 week (Expt II) after implantation of femoral arterial and venous catheters. ACTH and corticosteroid responses were assessed by RIA of arterial plasma samples. Arterial PO2 fell similarly in both experiments from 82 to 26 Torr. This caused significant increases in ACTH of similar magnitude in both experiments. Corticosteroid levels increased more in Expt I than Expt II indicating an apparent potentiation by surgery of the adrenocortical response to hypoxia. Two additional dogs were studied in reverse order under lighter anesthesia such that ACTH and corticosteroid levels after surgery were higher than in the first set of experiments. Under these conditions, hypoxia still produced a large increase in ACTH and corticosteroids after acute surgery. Correlation of log ACTH with corticosteroid levels (adrenal dose response) revealed a significant increase in slope in dogs with acute surgery suggesting that surgery interacted with hypoxia either to change the metabolic clearance rate of corticosteroid or to increase adrenal sensitivity to ACTH.

Adrenal Cortex Hormones↗
PubMed1982

Chemoreceptor involvement in cortisol responses to hypoxia in ventilated dogs.

Changes in cortisol secretion rate (CSR) in response to hypoxic hypoxia (HH) and to carbon monoxide hypoxia (COH) were assessed in mongrel dogs that had intact chemoreceptors (INT); surgically deafferented carotid bodies (CBD) or aortic bodies (ABD); or both carotid and aortic chemoreceptors denervated (SAD). All dogs were anesthetized, paralyzed, ventilated, and maintained normocapnic. In the INT and ABD groups, CSR responded "maximally" to HH, whereas in CBD and SAD animals, the CSR was attenuated but not eliminated. COH, which does not stimulate the carotid body, caused a submaximal increase in CSR regardless of chemoreceptor status. It is concluded that 1) the carotid bodies are the principal chemoreceptor influence on CSR during HH and 2) there is a nonchemoreceptor-mediated increase in CSR during hypoxia.

Adrenal Cortex↗
PubMed1981

ACTH and cortisol responses to hypoxia in dogs.

To determine the role of endogenous ACTH and hyperventilation in the adrenocortical response to hypoxia, pentobarbital-anesthetized dogs equipped with left adrenal venous cannulas for measurement of cortisol secretion rate (CSR) and arterial cannulas for measurement of plasma ACTH were exposed to 20 min of normoxia (group I), spontaneous ventilation, normocapnic hypoxic hypoxia (group II), controlled ventilation, normocapnic hypoxic hypoxia (group III), controlled ventilation, normocapnic carbon monoxide hypoxia (group IV), or hypoxic hypoxia with elevated carboxyhemoglobin (group V). Group I showed no change in ACTH and CSR. Groups II and III greatly increased CSR whereas only group III increased ACTH significantly. Group IV greatly increased ACTH whereas CSR increased but less than group III. Group V showed a significant increase in ACTH but no significant CSR response. In addition, 5 U of ACTh were infused in several animals from groups I, III, and IV. Exogenous ACTH caused increases in CSR that were larger in group I than groups III and IV. The data are consistent with the hypothesis that ACTH in arterial blood is not the sole controller of CSR during hypoxic stress.

Adrenocorticotropic Hormone↗