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Biomedical subjects

L G Moore

Publications and source records attributed to L G Moore.

At least 145 records · Page 8Linked to original sources

Effect of exogenous progestogens on plasma concentrations of the oxytocin-associated neurophysin and 13,14-dihydro-15-keto-prostaglandin F in intact and ovariectomized ewes over the time of expected luteal regression.

Plasma concentrations of the prostaglandin F metabolite 13,14-dihydro-15-keto-prostaglandin F (PGFM), the oxytocin-associated neurophysin (OT-N) and progesterone were monitored by radioimmunoassay (RIA) in five ewes sampled from the jugular vein at hourly intervals between 0700-1900 h from Days 12-16 of the estrous cycle. These hormones were also determined in plasma samples collected at similar times from five intact and five ovariectomized ewes given twice daily injections of medroxyprogesterone acetate (MPA) over Days 10 to 20 after the last observed estrus. In both the control and intact MPA-treated ewes, coincident surges of OT-N and PGFM were observed in jugular plasma during the time of luteal regression. No significant differences were noted in the number and amplitude of OT-N and number of PGFM peaks between the control and intact MPA-treated animals, although in the latter the amplitude of the PGFM peaks was significantly reduced (P less than 0.01). No marked surges in the plasma concentrations of PGFM or OT-N were observed in the ovariectomized ewes given exogenous MPA. This latter finding is consistent with previous proposals, suggesting that the ovaries are a major source of oxytocin in the ewe. In addition, the observation that exogenous progestogens in the intact ewes did not influence the number and peak height of the OT-N surges, indicates that a fall in progesterone levels during the normal cycle is not obligatory for oxytocin release although it may facilitate the release of uterine PGF2 alpha.

Animals↗

Development of radioimmunoassays for ovine neurophysins. Correlation of neurophysin release with oxytocin- and vasopressin-related stimuli.

Specific homologous RIAs for the ovine neurophysins (oN-I/II, oN-III) were established; the assays had a sensitivity capable of measuring basal levels of the pituitary proteins in sheep plasma. Reduction in blood volume of ewes caused a 200-fold increase in oN-III with minimal changes in oN-I/II levels. After infusion of either hypertonic saline or nicotine, a similar specific increase in oN-III was observed, occurring at a time when the free water clearance rate decreased. Intramuscular administration of estradiol benzoate caused an increase in jugular plasma oN-I/II concentrations without affecting the oN-III concentrations. In one of six lactating ewes, there was an increase in oN-I/II during suckling. The release of oN-I/II, which was accompanied by small increases in oN-III, exhibited a pulsatile profile similar to that reported for the secretion of oxytocin under similar conditions. During vaginal distension, increases in intramammary pressure were accompanied by elevations in levels of oN-I/II and oN-III. It is concluded that oxytocin-related events are associated predominantly with the release of oN-I/II and that stimuli that induce vasopressin release also cause elevation of oN-III. These correlations are consistent with our previous conclusion from biochemical and amino acid sequence analysis of the oNs.

Amino Acid Sequence↗

The incidence of pregnancy-induced hypertension is increased among Colorado residents at high altitude.

Both pregnancy-induced hypertension and high-altitude residence are associated with fetal growth retardation, thereby leading us to hypothesize that pregnancy-induced hypertension would be more common at high than at low altitude. Retrospectively collected data in Colorado revealed that pregnancy-induced hypertension was more common at 3,100 m (12%) than at 2,410 m (4%) or 1,600 m (3%) (P less than 0.001). Proteinuria and edema in the upper extremities were also more frequent at 3,100 m than at 1,600 m (proteinuria = 28% versus 9%, P less than 0.001; edema of upper extremities = 22% versus 13%, P less than 0.01). Blood pressure during pregnancy increased with altitude among all women and those without pregnancy-induced hypertension (analysis of variance, P less than 0.05). In a prospective study at 3,100 m, women with pregnancy-induced hypertension had no change in blood pressure during pregnancy prior to the onset of hypertension (analysis of variance, P = NS), whereas blood pressure decreased in the normal women (analysis of variance, P less than 0.05). Arterial oxygen saturation during the third trimester was inversely related to the degree of hypertension in women with pregnancy-induced hypertension at 3,100 m (r = 0.8, P less than 0.05), thus suggesting that maternal hypoxia may play a previously unsuspected role in the etiology of pregnancy-induced hypertension.

Adult↗

Embryonic suppression of oxytocin--associated neurophysin release in early pregnant sheep.

Pulsatile release of the oxytocin-neurophysin (OT-N) occurs during luteal regression in non-pregnant sheep. The effect on this neurophysin release by the presence of a conceptus was investigated. It was found that the transfer of an embryo, on either Day 12 or 13, to the uterus of a non-pregnant sheep inhibited the pulsatile release of OT-N. This result suggests that in the early pregnant sheep, the embryo may prevent corpus luteum regression by suppressing the pulsatile release of maternal oxytocin which is considered to induce the release of uterine prostaglandin F2 alpha.

Animals↗

Maternal hyperventilation helps preserve arterial oxygenation during high-altitude pregnancy.

We examined arterial oxygenation during pregnancy and 3 mo postpartum in 35 nonsmoking residents of Leadville, CO (elevation 3,100 m) to determine how well and by what mechanisms maternal arterial oxygenation was maintained during pregnancy at high altitude. Hyperventilation raised arterial O2 saturation above that in the nonpregnant state. Respiratory alkalosis persisted throughout pregnancy, shifting the O2-hemoglobin dissociation curve to the left, further facilitating O2 loading in the lung. However, a decrease in blood hemoglobin concentration and a slight increase in the alveolar-arterial O2 gradient in the late pregnancy caused the arterial O2 content to fall below that in the nonpregnant state. Compared to published sea level values, the Leadville women had higher ventilation and hemoglobin values, yielding arterial O2 contents as high as in pregnant women at sea level. Thus, ventilation and hemoglobin concentration were important variables contributing to O2 ttransport during pregnancy at high altitude.

Adult↗

Infant birth weight is related to maternal arterial oxygenation at high altitude.

Infant birth weight is reported to decrease at high altitude as a reulst of fetal growth retardation (McCullough, Reeves, and Liljegren. Arch. Environ, Health. 32: 36--39, 1977) but not all babies born at high altitude are small. We hypothesized that maternal characteristics acting to lower arterial O2 content would contribute to smaller infant birth weight. To test this hypothesis, we measured arterial oxygenation serially during pregnancy and again postpartum in 44 residents of Leadville, CO (elevation 3,100 m). We identified three maternal characteristics--ventilation, hemoglobin concentration, and smoking habits--that were related to the birth weight of the offspring. Mothers of smaller babies (less than 2,900 g) compared to mothers of larger babies (greater than 3,500 g) were characterized by hypoventilation, no change or a decrease in ventilation and arterial O2 saturation from early to late gestation, and a falling hemoglobin concentration that combined to lower arterial O2 content in the 3rd trimester. Maternal smoking at 3,100 m was associated with a two to threefold greater reduction in infant birth weight (-546 g) than reported from sea level. Thus, maternal arterial oxygenation during pregnancy may be important for predicting fetal growth retardation and the process of adaptation to high altitude.

Adaptation, Physiological↗

Pulmonary vascular reactivity is blunted in pregnant rats.

Pulmonary arterial pressure is decreased in pregnant women despite increased cardiac output, suggesting that pulmonary vascular resistance is decreased in pregnancy. To determine if pulmonary vascular reactivity is decreased in pregnant rats, lungs isolated from pregnant rats were perfused with blood from other pregnant rats at constant flow rate, and pressor responses to airway hypoxia and to angiotensin II were measured. Compared with responses obtained in lungs from nonpregnant female rats, hypoxic and angiotensin II pressor responses were blunted in pregnancy. To separate possible effects of pregnancy on the lung from those of substance(s) circulating in the blood in pregnancy, we perfused lungs from nonpregnant rats with blood from pregnant rats. Both the hypoxic and angiotensin II pressor responses were blunted by blood from pregnant rats. The angiotensin II pressor response was blunted also in lungs from pregnant rats perfused with blood from nonpregnant rats. These results suggest that a circulating substance is responsible for blunting of pulmonary vascular reactivity in pregnancy and that changes in the lung induced by pregnancy also depress angiotensin II responses. It is unlikely that estrogen and progesterone were responsible for these effects, since lungs and blood obtained from animals treated with these hormones did not have blunted pulmonary vascular reactivity.

Angiotensin II↗

Emphysema mortality is increased in Colorado residents at high altitude.

Emphysema mortality is higher in Colorado than in the nation as a whole despite the younger age of Colorado's population Colorado death records from 1959 to 1976 were examined to determine if emphysema mortality increases with altitude within the state and if altitude adversely affects survival from chronic lung disease. Because the proportion of persons older than 65 yr of age in Colorado decreases with altitude (r = -0.6, p less than 0.01), emphysema mortality was age-standardized. The age-standardized rate increases with altitude among males (r = 0.9, p less than 0.01; y = 0.003(x) + 42.1). Emphysema deaths at higher altitudes in Colorado (greater than or equal to 7,000 ft) occur at a younger age (68.1 +/- 0.6 yr (mean +/- SEM) versus 70.1 +/- 0.6 yr at lower altitudes), after a shorter duration of illness, and more commonly from cor pulmonale than at lower altitudes (less than or equal to 4,500 ft) where pneumonia is more common as the immediate cause of death. The mechanism by which high altitude residence interacts unfavorably with survival is not known but may stem from augmented pulmonary hypertension caused by the hypoxia of lung disease added to the hypoxia of high altitude.

Adult↗

Beneficial effect of rightward hemoglobin-oxygen dissociation curve shift for short-term high-altitude adaptation.

To determine whether a rightward shift of the ODC was beneficial for short-term high-altitude adaptation, 10 drug-treated subjects were compared in a double-blind manner to 10 placebo-treated subjects after ascent from Ann Arbor, Mich. (240 m) to the top of Pike's Peak, Colo. (4300 m). Subjects were normal, male residents at 240 m in good health. Phosphate (30 mmol, t.i.d.), vitamin C (500 mg, q.i.d.), and sodium bicarbonate (1.25 mEq/kg body weight) were administered in order to elevate 2,3-DPG levels and shift ODCs to the right before the ascent so that subjects with right-shifted ODCs could be contrasted with subjects whose ODCs were not right-shifted during the first 1 to 2 days at 4300 m. After 24 hr at 4300 m, 2,3-DPG levels were higher in drug-treated than in placebo-treated subjects (19.7 +/- 0.6 mmol/gm of hemoglobin vs. 18.5 +/- 0.4; p less than 0.05 by one-tailed test), and ODC positions were different after 6 hr at high altitude (one-tailed p less than 0.01). Drug-treated subjects felt better as measured by a symptomatology questionnaire and had better central nervous system function as measured by a darkness-adaptation visual task. Performance in the two groups of subjects was the same on other visual and cognitive psychometric tests. Cardiopulmonary responses to high altitude were comparable in the two groups. The small, though significant improvement in dark adaptation and symptoms in drug-treated subjects suggests that oxygenation of the brain may have benefited from the small-shift in ODC observed. Agents with greater effect on 2,3-DPG levels are deserving of trial to determine whether they have more substantial effects on short-term responses to high altitude.

Adaptation, Physiological↗

Temporal relationship between plasma concentrations of 13,14-dihydro-15-keto-prostaglandin F and neurophysin I/II around luteolysis in sheep.

Plasma concentrations of neurophysin I/II (N-I/II), 13,14-dihydro-15-keto-prostaglandin F (PGFM) and progesterone were measured by radioimmunoassay in plasma samples collected from four sheep at hourly intervals between 0700 and 1900 h from Days 12-17 of the estrous cycle. Plasma samples were also collected from a fifth sheep at 2-hourly intervals during Days 12-16 of the cycle. In all sheep, intermittent surges in the plasma concentrations of PGFM and N-I/II occurred during the period of luteal regression. On at least one occasion in each sheep a surge in the plasma concentration of N-I/II was observed coincident with a rise in PGFM concentrations. In general, the highest levels of N-I/II were observed early in luteolysis (Days 13-14 of the cycle) while the corresponding levels of PGFM in plasma were maximal around Day 15 when luteolysis was well advanced. It is suggested from this temporal data that oxytocin, which is considered to be released in association with N-I/II, may play an important role in ovine luteolysis by stimulating the secretion of prostaglandin F from the uterus during days 13-15 of the estrous cycle.

Animals↗

Pregnancy blunts pulmonary vascular reactivity in dogs.

Pregnancy decreases systemic vascular reactivity but comparatively little is known about the effects of pregnancy on the pulmonary circulation. Pulmonary vascular resistance (PVR) during acute hypoxia was lower (P < 0.01) in eight intact anesthetized pregnant dogs compared to the same animals postpartum. Mean pulmonary arterial pressure (Ppa) and PVR during infusion of prostaglandin (PG) F2 alpha were also reduced during pregnancy. Nonpregnant female dogs (n = 5) treated with estrogen (0.001 mg x kg-1 x da-1) for 2 wk had decreased Ppa (P < 0.01) during acute hypoxia compared to control measurements, but PVR was unchanged during hypoxia and PGF2 alpha infusion. Treatment with progesterone in four dogs had no effect on pulmonary vascular reactivity to hypoxia or PGF2 alpha. Inhibition of circulating PG with meclofenamate in four dogs during pregnancy did not appear to restore pulmonary vascular reactivity. Blunted pulmonary vascular reactivity is suggested by the limited data available for women, but is not seen in pregnant cows. We conclude that pregnancy decreases pulmonary as well as systemic vascular reactivity in the dog, but the mechanism is unclear.

Animals↗

Pregnancy-induced pulmonary hypertension in cows susceptible to high mountain disease.

Observations in several species suggest that pulmonary vascular reactivity may be reduced during pregnancy. We tested this hypothesis in two groups of unanesthetized cows, one "susceptible" and one "resistant" to high mountain or brisket disease. At the altitude of residence (1,524 m), mean pulmonary arterial pressure was elevated during pregnancy by 18% and total pulmonary vascular resistance by 32% in susceptible but not in resistant cows. During acute exposure to simulated altitudes of 2,120--4,550 m, pulmonary arterial pressure was increased by 16% and total pulmonary resistance by 28% during pregnancy in susceptible cows. The pulmonary pressor response to a 5 microgram/kg bolus of prostaglandin FIalpha was not different during pregnancy in either group. Resistant cows hyperventilated while pregnant, raising arterial partial pressure of oxygen (PaO2) by 6 Torr both at 1,524 m and, on the average, by 7 Torr at altitudes of 2,120--4,550 m. Susceptible cows increased their PaO2 less than did the resistant cows during pregnancy. The results indicated that pregnancy was associated with a greater rise in pulmonary arterial pressure and total pulmonary vascular resistance during acute hypoxia and failed to elicit as great a ventilatory response in susceptible than in resistant cows.

Altitude↗

Human llamas: adaptation to altitude in subjects with high hemoglobin oxygen affinity.

To assess the adaptive value of the right-shift of the oxyhemoglobin dissociation curve (decreased affinity for oxygen) observed in humans upon altitude exposure, the short-term physiologic responses to altitude-induced hypoxia were evaluated in two subjects with a high oxygen affinity hemoglobin (Hb Andrew-Minneapolis) and in two of their normal siblings. In striking contrast to normal subjects, at moderately high altitude (3,100 m) the high affinity subjects manifested: (a) lesser increments in resting heart rate; (b) minimal increases in plasma and urinary erythropoietin; (c) no decrement in maximal oxygen consumption; and (d) no thrombocytopenia. There was no difference between subject pairs in 2,3-diphosphoglycerate response to altitude exposure. These results tend to contradict the belief that a decrease in hemoglobin oxygen affinity is of adaptive value to humans at moderate altitudes. Rather, they support the hypothesis that, despite disadvantages at low altitude, a left-shifted oxyhemoglobin dissociation curve may confer a degree of preadaptation to altitude.

Adaptation, Physiological↗

Effects of high altitude on plasma concentrations of testosterone and pituitary gonadotropins in man.

Ten healthy male volunteers were rapidly taken to the top of Pike's Peak, altitude 14,100 ft (4,300 m) where they remained at the research station for 6 d. There were no significant changes, compared to their values at sea-level, in the plasma concentrations of testosterone, FSH, and LH during this period. There was a highly significant direct correlation between individual changes in testosterone and the gonadotropins on Day 1. Our data provide no evidence for an acute effect of high-altitude per se on the secretion of testosterone and the pituitary gonadotropins.

Adult↗