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Biomedical subjects

J R Claybaugh

Publications and source records attributed to J R Claybaugh.

At least 55 records · Page 3Linked to original sources

Vasopressin metabolism in the amniotic sac of the fetal guinea pig.

A route for fetal 8-arginine vasopressin (AVP) clearance has not yet been established. The results of this study indicate that in the fetal guinea pig, the amniotic sac is a site for AVP metabolism. When fetal plasma, urine, and amniotic fluid were fractionated on HPLC, AVP was identified only in fetal plasma and urine. In addition, when AVP and inulin were injected into the amniotic sac in vivo during the last week of gestation, the AVP to inulin ratio decreased (P less than 0.05) over a 2-h period, indicating a swallowing-independent disappearance of AVP. Furthermore, when tritiated AVP was similarly injected, the radioactivity to inulin ratio remained constant, suggesting that AVP was not diffusing out of the amniotic sac. Two hours after the injection into the amniotic sac, amniotic fluid was collected and fractionated by HPLC, and only 42% of the total radioactivity was intact AVP. The remainder was identified in two other products (M1 and M2). Tritiated AVP incubated with amniotic fluid and amnionic membrane in vitro produced both M1 and M2. Tritiated AVP incubated with amnionic membrane in artificial amniotic solution produced only M1. Tritiated AVP incubated in only amniotic fluid produced M2, with only slight M1 production. Thus, neither metabolite was necessary for the production of the other; M1 was amnionic membrane dependent, and M2 was amniotic fluid dependent. In conclusion, the amniotic sac may play a role in the clearance of AVP from the fetal system.

Amnion↗

Effects of exercise on atrial natriuretic factor. Release mechanisms and implications for fluid homeostasis.

Atrial natriuretic factor is reported to be elevated during and immediately following exercise and is thought to play a role in fluid homeostasis and cardiovascular regulation. The predominant stimuli for atrial natriuretic factor release during exercise appear to be increases in atrial pressures or atrial distension, both of which are reported to increase with exercise. The intensity and perhaps duration of exercise also influence the magnitude of the atrial natriuretic factor response. It is not clear if the rise in plasma atrial natriuretic factor during exercise plays any role in altering renal function since high intensity exercise is typically associated with an antidiuresis. However, elevations in plasma atrial natriuretic factor may in part be responsible for the increase in urine flow reported when exercise is performed at low or moderate intensities. Atrial natriuretic factor also has vascular effects which may be important in buffering or moderating the blood pressure response to exercise. The atrial natriuretic factor response to exercise and basal levels of the hormone are greatly elevated in patients who suffer from a variety of cardiovascular and pulmonary disease conditions. These elevated plasma atrial natriuretic factor values are associated with increases in atrial pressure and appear to be related to the severity of disease. Although much controversy exists regarding the renal and vascular effects of atrial natriuretic factor, the measurement of this hormone, particularly during exercise, may be of clinical value by providing an additional tool to evaluate patients and determine the effectiveness of various treatment regimens.

Atrial Natriuretic Factor↗

Role of cardiac nerves in response to head-out water immersion in conscious dogs.

The circulatory, renal, and hormonal responses during 100 min of thermoneutral (37 degrees C) head-out water immersion (WI) were investigated in conscious intact (INT) and cardiac-denervated (CD) dogs. In the INT group, both left and right atrial and aortic transmural distending pressures and left ventricular contractile performance (LV dP/dtmax) increased, and total peripheral resistance remained unchanged. Cardiac output (QCO) increased in association with an increase in heart rate and LV dP/dtmax. Urine flow (V), sodium excretion (UNaV), and osmolal clearance (Cosmol) all increased, whereas glomerular filtration rate, as indicated by creatinine clearance (CCr), remained constant. The diuresis and natriuresis occurred in the absence of any significant changes in plasma levels of antidiuretic hormone (ADH), aldosterone, or plasma renin activity. The CD animals showed a similar hemodynamic response except that the increase in QCO was now associated with an increase in stroke volume and no change in heart rate or LV dP/dtmax. Although the increase in V was similar in both magnitude and time course of the INT animals, there was no significant change in UNaV. Thus there is a striking change in the character of the response of the denervated group in that the natriuresis is abolished and, instead, a water diuresis occurred. Free water clearance increased, but no significant changes in Cosmol or CCr were observed. In addition plasma ADH levels significantly declined during WI in the CD group. These data indicate that cardiac receptors are important in determining the nature of the renal response to WI.

Animals↗

Regional circulatory responses to head-out water immersion in conscious dogs.

We determined the regional blood flow responses to head-out water immersion (WI) in intact (INT) and cardiac-denervated (CD) conscious dogs. Immersing dogs in thermoneutral water (37 degrees C) in the quadruped position for 100 min resulted in significant increases in cardiac output (Qco) above control values by 38.7% in the INT dogs and 39.2% in the CD dogs (P less than 0.01). Arterial pressure increased by 32 and 34.7% in the INT and CD groups, respectively, during WI, with no significant changes occurring in the calculated total peripheral resistance. Regional blood flow responses were measured with 15-microns radiolabeled microspheres. Flows in the INT and CD groups increased significantly to the heart (40, 38%), skin (93, 96%), fat (79, 83%), diaphragm (44, 48%), and intercostal muscles (58, 55%), whereas there were no changes in renal cortical blood flows during WI. Total brain blood flows did not change significantly on immersion; however, blood flows in both INT and CD animals were increased to the cerebellum (19, 22%), but a significant decrease in pituitary flow (52%) was observed only in the CD group during WI. Gastrointestinal tissue flows increased only during early WI in both INT (45%) and CD (47%) animals. However, blood flows to the skeletal muscles increased only during late WI in the INT (53%) and CD (47%) groups. There were no significant differences between the INT and CD groups. Rectal temperatures and systemic O2 consumption (VO2) were unchanged during WI in both groups of animals. These observations indicate that WI leads to a sustained elevation of Qco accompanied by selective increases in regional tissue perfusion that may be accounted for in some tissues by an increase in metabolic demand or by local heating responses and produces a time-dependent redistribution of blood flow away from the gastrointestinal tissues toward skeletal muscle tissues, which may be due to a partial uncoupling of the normal Q/VO2 relationship. This may be caused by thermal or central neurohumoral mechanisms. These regional circulatory responses are not dependent on the presence of the cardiac nerves.

Animals↗

Hormonal and vascular fluid responses to maximal exercise in trained and untrained males.

The trained condition is associated with alterations in fluid regulation. In attempt to elucidate mechanisms responsible for these differences, resting, postexercise (maximal treadmill exercise of 8-13 min duration), and recovery measurements were made in seven trained (mean peak O2 consumption was 60.5 +/- 1.6 ml.kg-1.min-1) and seven untrained (mean peak O2 consumption was 40.7 +/- 1.7 ml.kg-1.min-1) male subjects. Samples were obtained by venipuncture with subjects seated. No significant differences in resting plasma osmolality (Osm), sodium, potassium, antidiuretic hormone (ADH), aldosterone, renin activity, or atrial natriuretic factor were found between groups. Maximal exercise produced significant increases in all of the above variables. Values immediately postexercise were similar between groups except for plasma Osm and sodium, which were significantly higher in the untrained group. Despite a reduction in plasma volume of equal magnitude in both groups, trained subjects demonstrated an increase in vascular proteins and mean corpuscular volume during exercise. This increase in plasma protein may be an important initiating factor responsible for the elevated plasma volume after 1-h recovery from exercise in the trained group. Lastly, similar ADH responses despite lower Osm in trained subjects may indicate that training increases the sensitivity of ADH to osmotic stimulation.

Adult↗

Atrial natriuretic factor inhibits vasopressin secretion in conscious sheep.

To test the hypothesis that atrial natriuretic factor (ANF) has a centrally mediated action on body fluid homeostasis, the effects of intracerebroventricularly (ICV) infused ANF on plasma vasopressin (AVP) concentration and urinary water and electrolyte excretion were investigated in euhydrated and water-deprived conscious sheep. ICV ANF decreased plasma AVP concentration and increased urinary free water excretion in euhydrated sheep, with excretion of Na and K unaltered. However, ICV ANF did not affect urinary volume, free water clearance, or excretion of Na and K in dehydrated animals, although plasma AVP concentration was significantly decreased. The relationship between urine volume and plasma AVP concentration was fitted by a power curve: urine volume = 0.79 X [AVP]-0.71; urine volume changes very little as a function of AVP concentration at the higher ranges. Intravenous infusion of the same amount of ANF was without effect on plasma AVP concentration or urinary excretion in both euhydrated and dehydrated animals. Mean arterial pressure was unchanged throughout all experiments. These results are consistent with the hypothesis that central ANF inhibits AVP secretion.

Animals↗

Seadragon VI: a 7-day dry saturation dive at 31 ATA. III. Alterations in basal and circadian endocrinology.

Four male divers were exposed to an environment of 1 ATA air for 7 d, followed by 7 d of 31 ATA He-O2, and following decompression to a postdive 1 ATA air environment for 3 d. Urine and blood were collected for hormonal measurements. Divided 24-h urine collections were obtained during 3 consecutive d at predive 1 ATA conditions, and at 31 ATA conditions. Two consecutive day collections were obtained at early decompression (31-25 ATA), at late decompression (14-8 ATA), and at postdive 1 ATA. Two blood samples were obtained, at predive 1 ATA, at 31 ATA, and at postdive 1 ATA. Plasma antidiuretic hormone (ADH) concentration decreased about 45% (P less than 0.005), while plasma aldosterone concentration and urinary aldosterone excretion were doubled (P less than 0.005) after the subjects were at 31 ATA. Plasma cortisol concentration and plasma parathyroid hormone concentration were not significantly affected by hyperbaria. Urinary excretion of aldosterone was not significantly different between day (0700-1900) and night (1900-0700) at any time, and both day and night excretion rates were increased at 31 ATA through late decompression (P less than 0.005). Urinary ADH excretion was greater during daytime at predive 1 ATA (P less than 0.005), but not thereafter. Both daytime and nighttime ADH excretion rates were decreased from 31 ATA through late decompression (P less than 0.005). It is concluded that hyperbaria eliminates the circadian release pattern of ADH and that the overall reduction of ADH may contribute to the increased free water clearance observed at hyperbaria. Also, increased parathyroid hormone was not associated with the phosphaturia observed at hyperbaria, but increased aldosterone coexisted with the increased kaliuresis observed.

Adult↗

Seadragon VI: a 7-day dry saturation dive at 31 ATA. VI. Hyperbaria enhances renin but eliminates ADH responses to head-up tilt.

Three male subjects were passively tilted from a supine to a 90 degree head-up standing position on 2 d each at 1 and 31 ATA, then on 1 d of the postdive period. On each day the subjects were tilted once in the morning (0800-1000) and once in the evening (2000-2200). Before each tilt experiment, the subjects were first intravenously cannulated for blood sampling, then assumed the supine position. A blood sample was taken after 10 min in the supine position, and another sample was taken after 15 min of motionless, supported standing. The plasma was analyzed for antidiuretic hormone (ADH), plasma renin activity (PRA), plasma cortisol, and aldosterone. ADH, PRA, and cortisol were significantly increased by tilt, but the responses varied with time of day or atmospheric pressure. Cortisol increased only in the morning tilt (P less than 0.005) and was not affected by pressure. At 1 ATA, PRA was elevated in the morning tilt experiment (P less than 0.005) and not the evening tilt, but the overall response to tilt was greater at 31 ATA than at 1 ATA (P less than 0.005). The ADH response to tilt (P less than 0.025) was unaffected by time of day, but was eliminated at 31 ATA. The basal levels of ADH were also lower at 31 ATA (P less than 0.005). The mechanism of these responses remains unclear, but the eliminated postural stimulation of ADH may account for the eliminated circadian excretory pattern of the hormones. The altered responses to body fluid shifts possibly contribute to the increased aldosterone and decreased ADH frequently observed at hyperbaria.

Adult↗

Seadragon VI: a 7-day dry saturation dive at 31 ATA. II. Characteristics of diuresis and nocturia.

Four male divers were exposed to a dry, 31 ATA, He-O2 environment for 7 d (Seadragon VI). Urine was collected diurnally (0700-2200 h) and nocturnally (2200-0700 h) before (predive 1 ATA air), during, and after (decompression and postdive 1 ATA air) exposure to 31 ATA. A typical hyperbaric diuresis associated with a reduction in urine osmolality was observed in the face of a constant creatinine clearance. A significant increase (P less than 0.05) in osmolal clearance (COSM) was observed with concomitant decrease (P less than 0.05) in negative free water clearance, indicating that the diuresis has both osmotic and free water components. Although urine flow increased at pressure during both day and night, its magnitude was twofold greater at night as compared to daytime. Moreover, the diurnal diuresis was entirely due to an increase in free water excretion, whereas the nocturnal diuresis was largely due to an increased COSM. These results indicate that hyperbaric diuresis is induced by inhibition of tubular reabsorption of free water during daytime and of certain solutes during the night. Approximately 80% of the nocturnal increase in the excretion of osmotic substances was accounted for by Na, K, Cl, and urea.

Adult↗

Cardiorenal-endocrine responses to head-out immersion at night.

Cardiorenal-endocrine responses to 3-h head-out immersion (HOI) (water temperature = 34.5 +/- 0.5 degrees C) were studied during day (0900-1400 h) and night (2300-0400 h) in six hydropenic male human subjects. Although HOI induced a reversible increase in urine flow in all subjects, the response was faster and greater in magnitude during the day compared with night (P less than 0.05). Na excretion and osmolal clearance (Cosm) also followed the identical response pattern as urine flow, and in fact, the HOI-induced diuresis was entirely accounted for by the increased Cosm. Endogenous creatinine clearance was not different between the day and the night and remained unchanged during HOI. Both plasma renin activity and aldosterone concentration and urinary aldosterone excretion were nearly twofold greater during the day compared with night before HOI but decreased to the same level during HOI in both daytime and the nighttime series (P less than 0.05). There was no correlation between the Na excretion rate and renin-aldosterone levels either before or during HOI. Plasma antidiuretic hormone (ADH) level was comparable between day and night before HOI and decreased to a similar level during HOI in both daytime and nighttime series (P less than 0.05 for nighttime HOI). Cardiac output increased from 3.3 1/min before HOI to 5-6 1/min during HOI without showing any significant circadian difference. Hematocrit, hemoglobin, and plasma concentrations remained unchanged under all conditions. It is concluded that the renal response to HOI is subject to nocturnal inhibition, which cannot be attributed to circadian differences in the degree of HOI-induced central blood pooling, renin-aldosterone, or ADH responses.

Adult↗

Fluid conservation in athletes: responses to water intake, supine posture, and immersion.

The roles of antidiuretic hormone (ADH) and aldosterone in the elicited diuretic responses of trained and untrained men to seated, supine, and head-out water immersed conditions were studied. Volunteers were comprised of groups of six untrained individuals, six trained swimmers, and six trained runners. Each subject underwent three protocols, six hours in a seated position, supine position, or immersion (35 degrees C water). The last two protocols were preceded and followed by 1 h of seated position. After 10 h of fasting, 0.5% body wt of water was drunk. One hour later the trained groups had higher urine osmolalities (P less than 0.05) and urinary excretion rates of ADH (P less than 0.05) and lower urine flow rates (P less than 0.05) than untrained subjects. Throughout the sitting protocol, urinary ADH was also higher in both trained groups (P less than 0.05). Both supine posture and immersion resulted in significant decreases in urinary ADH in the untrained subjects (P less than 0.05) but no changes wer noted in swimmers and only during the second hour of immersion in the runners (P less than 0.05). The natriuresis and kaliuresis were greater during immersion than in the supine position but plasma renin activity, measured only in trained groups, and plasma aldosterone, measured in the untrained group, were decreased similarly with both protocols. The increases in urinary sodium excretion and urine flow rate were lower in trained than untrained subjects during the supine and immersion protocols (P less than 0.05). The data are compatible with an increased osmotic but decreased volume sensitivity of ADH control in trained men.

Adult↗

Cardio-renal responses to a stimulated gravity-free state induced by water immersion.

HOI induces a significant increase in the cardiac output, which is accompanied by increases in the urinary excretion of water, Na and K. However, the renal responses are not always associated with the cardiac response, suggesting a possible dissociation of two events. Although the urinary excretion of both ADH and aldosterone decreases during HOI, the mechanism for these changes is not clearly understood. The renal responses to HOI, especially the natriuresis, is considerably attenuated in endurance-trained athletes, which may be related to the more moderate inhibition of both ADH and renin-aldosterone systems. The exact role of the cardiac receptors in inducing the renal responses to HOI is still not defined, although the latter receptors are involved in inducing the natriuresis. Finally, important diurnal variations have been demonstrated for the renal responses to HOI, and elucidation of the mechanism for this interesting phenomenon may help understand the overall mechanisms for the development of cardiorenal-endocrine responses to HOI.

Aldosterone↗

Factors influencing urinary vasopressin concentration.

Vasopressin (VP) activity has been measured in urine for assessments of long-term changes in hormone release. Most laboratories employ radioimmunoassays (RIAs) and extraction of urine for research. It has been assumed that the specificity of the antiserums used and the extraction procedures would be adequate to safeguard against non-VP substances that would interfere with the RIA. New evidence is presented that this is probably not the case. High-performance liquid chromatography of unextracted urine or CG-50 extracts of urine clearly separates two major immunologically active peaks. One corresponds to native VP and the other migrates with the front. Different antiserums recognize the non-VP peak variably, but the VP peak the same. These activities were not separated by Sephadex G-25 chromatography. In addition to variability arising in the measurement of VP, the VP excreted may be influenced by variable renal clearance of the hormone. There is ample evidence to assume that not all plasma VP is filterable and that the proportions of bound and unbound VP vary. Furthermore, there is tubular metabolism and secretion of VP. The variability of these functions is unknown.

Animals↗

Responses of salt- and water-regulating hormones during a saturation dive to 31 ATA (SEADRAGON IV).

Four Japanese male subjects were studied during 3 days at 1 ATA, 3 days of compression to 31 ATA (1000 fsw), 14 days at 31 ATA, 12 days of decompression, and 3 days of postdive control at 1 ATA. The chamber was maintained at thermoneutral temperatures. During the 31-ATA exposure, urine flow increased about 500 ml/day (P less than 0.05) accompanied by an approximate 500-ml/day increase in osmotic clearance (Cosm) (P less than 0.05). Both urine flow and Cosm increases were primarily attributable to an increase in the overnight flow rates (P less than 0.01). The negative free water (-CH2O)/Cosm decreased during exposure to 31 ATA, indicating that a reduction in tubular water reabsorption may also contribute to the diuresis. Urine flow, Cosm, and -CH2O/Cosm all returned to predive values during decompression to 1 ATA. The urinary excretion rate of aldosterone increased from 2.7 +/- 0.3 micrograms/day at 1 ATA to 4.3 +/- 0.0 micrograms/day (P less than 0.01) at 31 ATA, remaining at about 3.8 micrograms/day until decompression. Urinary antidiuretic hormone (ADH) decreased from 50 +/- 7 to 33 +/- 3 mU/day (P less than 0.01) upon compression to 31 ATA and continued to decrease throughout the decompression phase. Plasma renin activity was increased by twofold (P less than 0.01) and plasma aldosterone by about 37% (NS) during exposure to 31 ATA. It is concluded that the reduction in ADH does not contribute significantly to the hyperbaric diuresis, and that the increased activity of the renin-angiotensin-aldosterone is a result of other postulated mechanisms resulting in an increased Cosm.

Adult↗

Antidiuretic hormone responses to eucapnic and hypocapnic hypoxia in humans.

Urinary excretion rate of antidiuretic hormone (UADHV) was studied in male volunteers in response to hypobaric hypoxia. The first series consisted of three groups. The chamber was decompressed to 465, 495, and 438 Torr during high-altitude (HA) exposure for groups I (n = 5), II (n = 5), and III (n = 4), respectively. In group I, the chamber air contained 3.77% CO2 to prevent alkalosis. The level of hypoxemia was similar in groups I and II. Mean 24-h UADHV was unchanged in group I, but increased 96% (P less than 0.05) and 180% (P less than 0.05) in groups II and III, respectively, on day 1 at HA and was normal during subsequent days at HA regardless of symptoms of acute mountain sickness. Shorter sampling intervals employed in a second series of experiments conducted at 495 Torr revealed a twofold increase in UADHV (P less than 0.05) 8-12 h after ascent in eight asymptomatic subjects; UADHV returned to base line within 9 h and remained low. The symptomatic subjects both had increased UADHV (3- and 8-fold from base line) between 2 and 4 h after ascent. Increased UADHV in asymptomatic subjects may be a result of the concomitant decrease in plasma volume, both of which appeared to be eliminated by CO2 supplementation.

Adult↗

Role of dopamine in the angiotensin II-induced vasopressin release in the conscious dehydrated dog.

The effect of the dopamine antagonist, haloperidol, on arginine-vasopressin (AVP) release induced by angiotensin II was studied in six dehydrated conscious dogs. Angiotensin II (10 ng/kg per min) alone caused a twofold increase (P less than 0.05) in plasma AVP concentration, a 25 mmHg increase (P less than 0.01) in mean arterial blood pressure (ABP) and a 70% decrease (P less than 0.01) in plasma renin activity (PRA). In the presence of haloperidol (3 micrograms/kg per min), angiotensin II caused similar changes in mean ABP (25 mmHg; P less than 0.01) and PRA (-65%, P less than 0.01), but a small insignificant decrease in plasma AVP (-22%). The AVP response to angiotensin II in the presence of haloperidol was significantly (P less than 0.05) different from its response to angiotensin II alone. Neither haloperidol alone nor the two vehicles had any effect on plasma AVP or mean ABP but PRA dropped slightly. The results suggest that a dopaminergic mechanism may be involved in angiotensin II-induced AVP release.

Angiotensin II↗

Renal function, aldosterone, and vasopressin excretion following repeated long-distance running.

Renal and endocrine responses were studied in 10 male runners during a 20-day 500-km race. Overnight urine and prerun blood samples were taken prior to running on days 1, 2, 5, 8, 14, 17, and 20. Day 13 followed 70 h of rest. Urine flow rate, osmotic clearance, tubular free water reabsorption, urinary vasopressin excretion rate, and body weight were not significantly changed. Creatinine clearance was constant except for an elevation on day 5. Plasma osmolality was elevated on days 2, 14, and 17. Plasma sodium was increased (P less than 0.05) on days 2 and 13 but reduced on day 20. The percentage of filtered sodium excreted was significantly reduced on all nights following running and elevated on recovery day 13. Urinary aldosterone excretion rate was significantly elevated 162, 117, and 97% on days 5, 8, and 20 and returned to control levels on day 13 after 70 h of rest. These data suggest that in response to repeated long-distance running normal fluid balance is regained within 12 h. However, it is necessary to conserve sodium for at least 24 h after exercise as evidenced by the decrease in the percent filtered sodium excreted and continued elevation of aldosterone excretion.

Adult↗