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L G Moore

Publications and source records attributed to L G Moore.

At least 37 records · Page 2Linked to original sources

Chronic hypoxia, pregnancy, and endothelium-mediated relaxation in guinea pig uterine and thoracic arteries.

Vasodilation that occurs during normal pregnancy is associated with enhanced relaxation and decreased contractile response to agonists, which are in part due to increased stimulated and basal nitric oxide (NO). In preeclampsia and/or pregnancies carried at high altitude (HA), this normal vascular adjustment is reversed or diminished. We previously reported that HA exposure did not inhibit the pregnancy-associated decrease in contractile response to agonist or basal NO in guinea pig uterine arteries (UA). We therefore sought to determine whether altitude interfered with effects of pregnancy on endothelium-dependent relaxation through a reduction in stimulated NO. We examined the relaxation response to ACh in UA and bradykinin in thoracic arteries (TA) and effects of NO inhibition with 200 microM N(G)-nitro-L-arginine (L-NNA) in arterial rings isolated from nonpregnant and pregnant guinea pigs exposed throughout gestation to low altitude (LA, 1,600 m, n = 26) or HA (3,962 m, n = 22). In pregnant UA, relaxation to ACh was enhanced (P < 0.05) at both altitudes and NO inhibition diminished, but did not reverse, ACh relaxation. The effect of L-NNA on the relaxation response to ACh was less in HA than in LA animals (P = 0.0021). In nonpregnant UA, relaxation to ACh was similar in LA and HA animals. L-NNA reversed the relaxation response to ACh at HA but not at LA. In TA, relaxation to bradykinin was unaltered by pregnancy or altitude and was completely reversed by NO inhibition. These data suggest that effects of NO inhibition are diminished in UA during pregnancy at HA. Additional studies are needed to confirm whether these effects are mediated through inhibition of stimulated NO. HA exposure did not inhibit relaxation to ACh, perhaps because of stimulation of other vasodilators.

Altitude↗

Women at altitude: carbohydrate utilization during exercise at 4,300 m.

To evaluate the hypothesis that exposure to high altitude would reduce blood glucose and total carbohydrate utilization relative to sea level (SL), 16 young women were studied over four 12-day periods: at 50% of peak O(2) consumption in different menstrual cycle phases (SL-50), at 65% of peak O(2) consumption at SL (SL-65), and at 4,300 m (HA). After 10 days in each condition, blood glucose rate of disappearance (R(d)) and respiratory exchange ratio were measured at rest and during 45 min of exercise. Glucose R(d) during exercise at HA (4.71 +/- 0.30 mg. kg(-1). min(-1)) was not different from SL exercise at the same absolute intensity (SL-50 = 5.03 mg. kg(-1). min(-1)) but was lower at the same relative intensity (SL-65 = 6.22 mg. kg(-1). min(-1), P < 0.01). There were no differences, however, when glucose R(d) was corrected for energy expended (kcal/min) during exercise. Respiratory exchange ratios followed the same pattern, except carbohydrate oxidation remained lower (-23.2%, P < 0.01) at HA than at SL when corrected for energy expended. In women, unlike in men, carbohydrate utilization decreased at HA. Relative abundance of estrogen and progesterone in women may partially explain the sex differences in fuel utilization at HA, but subtle differences between menstrual cycle phases at SL had no physiologically relevant effects.

Adult↗

Women at altitude: energy requirement at 4,300 m.

To test the hypotheses that prolonged exposure to moderately high altitude increases the energy requirement of adequately fed women and that the sole cause of the increase is an elevation in basal metabolic rate (BMR), we studied 16 healthy women [21.7 +/- 0.5 (SD) yr; 167.4 +/- 1.1 cm; 62.2 +/- 1.0 kg]. Studies were conducted over 12 days at sea level (SL) and at 4,300 m [high altitude (HA)]. To test that menstrual cycle phase has an effect on energetics at HA, we monitored menstrual cycle in all women, and most women (n = 11) were studied in the same phase at SL and HA. Daily energy intake at HA was increased to respond to increases in BMR and to maintain body weight and body composition. Mean BMR for the group rose 6.9% above SL by day 3 at HA and fell to SL values by day 6. Total energy requirement remained elevated 6% at HA [ approximately 670 kJ/day (160 kcal/day) above that at SL], but the small and transient increase in BMR could not explain all of this increase, giving rise to an apparent "energy requirement excess." The transient nature of the rise in BMR may have been due to the fitness level of the subjects. The response to altitude was not affected by menstrual cycle phase. The energy requirement excess is at present unexplained.

Adult↗

Isoforms and half-life of FSH from sheep with different reproductive states.

The glycoprotein hormone FSH comes in many different isoforms. In humans and rats the charges of the FSH isoforms vary with reproductive state and these affect the half-life of FSH in plasma. In this study we examined the charge heterogeneity of FSH in pituitary extracts from sheep with different reproductive states. Also the half-life of clearance of pituitary FSH from the different reproductive states was determined in mice. Pituitaries were collected from: anoestrous, luteal phase, follicular phase, early-pregnant and late-pregnant ewes, ewe lambs, ram lambs, rams during the breeding and non-breeding seasons and wethers (5 per group). After extraction, FSH isoforms were fractionated by HPLC anion exchange chromatography. The volume at which half of the FSH had eluted from the ion exchange column was determined (HP(50)). It was found that FSH isoforms from ewes (HP(50)=96.7+/- 1.3 ml (s.e.m. )) eluted later (P<0.01) than those from rams (HP(50)=82.3+/-1.3 ml) indicating that FSH isoforms in the ewes were more acidic than those from rams. There was a seasonal difference in ewes, with ewes in anoestrus (HP(50)=101.6+/-2.6 ml) having more-acidic (P<0.01) FSH isoforms than the ewes during the oestrous cycle (HP(50)=95.3+/-0.7 ml). There was an effect of age, with the FSH isoforms from cycling ewes (HP(50)=95.3+/- 0.7 ml) being more acidic (P<0.01) than those from ewe lambs (HP(50)=88.3+/-1.9 ml). There was an effect of pregnancy, with late-pregnant ewes (HP(50)=107.3+/- 1.6 ml) having more-acidic FSH isoforms (P<0.05) than those from anoestrous ewes (HP(50)=101.6+/-2.6 ml) and there was an effect of castration with the breeding season rams (HP(50)=80.7+/-1.4 ml) having more-acidic (P<0.05) FSH isoforms than wethers (HP(50)=74.0+/-0.5 ml). The half-life of pituitary FSH from animals in the different reproductive states was found to be negatively correlated with HP(50) (r(2)=0.56, P<0.01). The FSH isoforms from wethers were the least acidic and had the longest half-lives. Collectively, these findings show that in sheep, age, sex and reproductive state are all factors which influence the forms of FSH that are extracted from the pituitary gland. Moreover, these results demonstrate that FSH from sheep with the most-acidic FSH isoforms have the shortest half-life in plasma.

Aging↗

Intraocular pressure and acclimatization to 4300 M altitude.

BACKGROUND: Studies were conducted to determine the effect of altitude exposure on intraocular pressure (IOP) and any relationship with the severity of acute mountain sickness (AMS). HYPOTHESES: a) IOP is decreased during exposure to 4300 m altitude; b) there is a positive correlation between IOP and AMS; and c) there is a correlation between changes in urinary catecholamines and IOP. METHODS: IOP (noncontact tonometry) was measured in 11 resting males during acute simulated altitude (446 mmHg, < 2 h, hypobaric chamber), during altitude acclimatization (15 d at 4300 m), and in 6 of the 11 volunteers during re-exposure in the chamber after 8 d at sea level (Study A). In a second study (Study B) of 12 females, IOP (contact tonometry) and 24-h urinary catecholamines were measured during a 50-h chamber exposure (446 mmHg). AMS severity was assessed using the Environmental Symptoms Questionnaire (ESQ-C). RESULTS: IOP decreased 25% after 2 d at altitude and returned toward sea level values by 15 d (Study A). IOP was reduced 13% after 5 h of exposure followed by return toward sea level values (Study B). Significant correlation was found between the sea level IOP and ESQ-C (Study A); significant correlation was found between the reduction in IOP and the ESQ-C and urinary epinephrine concentrations (Study B). CONCLUSIONS: Altitude exposure resulted in a reduction in IOP that occurred within hours and recovered during acclimatization. This reduction may be related to increases in epinephrine concentration. Measurement of IOP before and during altitude exposure may provide an objective method of assessing an individual's response to hypoxic stress.

Acclimatization↗

Altered blood pressure course during normal pregnancy and increased preeclampsia at high altitude (3100 meters) in Colorado.

OBJECTIVE: Our purpose was to determine the case incidences of preeclampsia at low and high altitudes and whether maternal blood pressure course during pregnancy differs between low and high altitudes. STUDY DESIGN: This was a retrospective cohort study of pregnancies in sociodemographically matched communities at low and high altitudes in Colorado; each community had a small hospital served by family practitioners and was located >100 miles from major urban areas. Included were consecutive singleton pregnancies of women without chronic disease that resulted in live-born infants at >28 weeks' gestation during an 18-month period (n = 116 at 1260 m, n = 93 at 3100 m). Clinic and hospital medical records were searched and data pertaining to hypertensive complications of pregnancy and serial blood pressure measurements were abstracted. RESULTS: Despite similar maternal risk factors, the case incidences of preeclampsia were 16% at 3100 m and 3% at 1260 m. As in sea-level pregnancies, mean blood pressure fell until week 20 in normotensive pregnancy at 1260 m. Mean pressure rose linearly, however, in normotensive women at 3100 m and in women with preeclampsia at both 1260 m and 3100 m. High altitude acted independently of known risk factors and yielded an odds ratio for preeclampsia of 3.6 (95% confidence interval 1. 1-11.9). Birth weight was 285 g lower at 3100 m despite similar gestational ages. CONCLUSION: The normal pregnancy-associated fall in blood pressure was absent at 3100 m, even in women who remained normotensive. The incidence of preeclampsia was increased at high altitude. Residence at high altitude interferes with the normal vascular adjustments to pregnancy, increasing the incidence of preeclampsia, and is perhaps analogous to other conditions that decrease uteroplacental oxygen delivery.

Adolescent↗

Slower fatigue and faster recovery of the adductor pollicis muscle in women matched for strength with men.

In previous gender comparisons of muscle performance, men and women rarely have been closely matched, absolute force has not been equalized, and rates of fatigue and early recovery have not been determined. We compared adductor pollicis muscle performance at a similar absolute force development in healthy men and women (both n=9) matched for adductor pollicis maximal voluntary contraction (MVC) force (132 +/- 5 N for women and 136 +/- 4 N for men, mean +/- SE, P > 0.05). Subjects repeated static contractions at a target force of approximately 50% of MVC force of rested muscle (68 +/- 3 N or 51.9 +/- 1.0% MVC for women and 72 +/- 2 N or 53.0 +/- 2.0% MVC for men, P > 0.05) for 5 s followed by 5 s rest until exhaustion, i. e. inability to maintain the target force for 5 s. MVC force was measured following each minute of exercise, at exhaustion, and after each minute for 3 min of passive recovery. For women compared with men: MVC force fell less after 1 min of exercise (to 93 +/- 1% vs. 80 +/- 3% of MVC force of rested muscle, respectively, P < 0.05); MVC force (N min-1) fell approximately 2-fold slower (P < 0.05); and endurance time to exhaustion was nearly two times longer (14.7 +/- 1. 6 min vs. 7.9 +/- 0.7 min, P < 0.05). After declining to a similar level of MVC force of rested muscle at exhaustion (56 +/- 1% for women and 56 +/- 3% for men), MVC force rose faster in women than in men (to 71 +/- 2% vs. 65 +/- 3% of MVC force of rested muscle, respectively; P < 0.05) during the first minute of recovery. The findings are consistent with the hypothesis that slower adductor pollicis muscle fatigue in women is linked with differences between men and women both in impairment of force generating capacity, per se, and in rates of recovery between contractions.

Adult↗

Human adaptation to high altitude: regional and life-cycle perspectives.

Studies of the ways in which persons respond to the adaptive challenges of life at high altitude have occupied an important place in anthropology. There are three major regions of the world where high-altitude studies have recently been performed: the Himalayas of Asia, the Andes of South America, and the Rocky Mountains of North America. Of these, the Himalayan region is larger, more geographically remote, and likely to have been occupied by humans for a longer period of time and to have been subject to less admixture or constriction of its gene pool. Recent studies of the physiological responses to hypoxia across the life cycle in these groups reveal several differences in adaptive success. Compared with acclimatized newcomers, lifelong residents of the Andes and/or Himalayas have less intrauterine growth retardation, better neonatal oxygenation, and more complete neonatal cardiopulmonary transition, enlarged lung volumes, decreased alveolar-arterial oxygen diffusion gradients, and higher maximal exercise capacity. In addition, Tibetans demonstrate a more sustained increase in cerebral blood flow during exercise, lower hemoglobin concentration, and less susceptibility to chronic mountain sickness (CMS) than acclimatized newcomers. Compared to Andean or Rocky Mountain high-altitude residents, Tibetans demonstrate less intrauterine growth retardation, greater reliance on redistribution of blood flow than elevated arterial oxygen content to increase uteroplacental oxygen delivery during pregnancy, higher levels of resting ventilation and hypoxic ventilatory responsiveness, less hypoxic pulmonary vasoconstriction, lower hemoglobin concentration, and less susceptibility to CMS. Several of the distinctions demonstrated by Tibetans parallel the differences between natives and newcomers, suggesting that the degree of protection or adaptive benefit relative to newcomers is enhanced for the Tibetans. We thus conclude that Tibetans have several physiological distinctions that confer adaptive benefit consistent with their probable greater generational length of high-altitude residence. Future progress is anticipated in achieving a more integrated view of high-altitude adaptation, incorporating a sophisticated understanding of the ways in which levels of biological organization are articulated and a recognition of the specific genetic variants contributing to differences among high-altitude groups.

Adaptation, Physiological↗

Superior exercise performance in lifelong Tibetan residents of 4,400 m compared with Tibetan residents of 3,658 m.

Few environments challenge human populations more than high altitude, since the accompanying low oxygen pressures (hypoxia) are pervasive and impervious to cultural modification. Work capacity is an important factor in a population's ability to thrive in such an environment. The performance of work or exercise is a measure of the integrated functioning of the O2 transport system, with maximal O2 uptake (.VO2max) a convenient index of that function. Hypoxia limits the ability to transport oxygen: maximal O2 uptake decreases with ascent to high altitude, and years of high altitude residence do not restore sea level .VO2max values. Since Tibetans live and work at some of the highest altitudes in the world, their ability to exercise at very high altitude (>4,000 m) may define the limits of human adaptation to hypoxia. We transported 20 Tibetan lifelong residents of > or =4,400 m down to 3,658 m in order to compare them with 16 previously studied Tibetan residents of Lhasa (3,658 m). The two groups of Tibetans were matched for age, weight, and height. All studies were performed in Lhasa within 3 days of the 4,400 m Tibetans' arrival. Standard test protocol and criteria were used for attaining .VO2max on a Monark bicycle ergometer, while measuring oxygen uptake (.VO2, ml/kg - min STPD), heart rate (bpm), minute ventilation (VE, 1/min BTPS), and arterial oxygen saturation (SaO2, %). The 4,400 m compared with 3,658 m residents had, at maximal effort, similar .VO2 (48.5 +/- 1.2 vs. 51.2 +/- 1.4 ml/kg - min, P = NS), higher workload attained (211 +/- 6 vs. 177 +/- 7 watts, P < 0.01), lower heart rate(176 +/- 2 vs. 191 +/- 2 bpm, P < 0.01), lower ventilation (127 +/- 5 vs. 149 +/- 5 l/min BTPS, P < 0.01), and similar SaO2(81.9 +/- 1.0 vs. 83.7 +/- 1.2%, P = NS). Furthermore, over the range of submaximal workloads, 4,400 m compared with 3,658 m Tibetans had lower .VO2 (P < 0.01), lower heart rates (P < 0.01), and lower ventilation (P < 0.01) and SaO2 (P < 0.05). We conclude that Tibetans living at 4,400 m compared with those residing at 3,658 m achieve greater work performance for a given .VO2 at submaximal and maximal workloads with less cardiorespiratory effort.

Adult↗

Temporal relationships between hormonal and hemodynamic changes in early human pregnancy.

BACKGROUND: The systemic hemodynamic profile of human pregnancy is characterized by a decrease in mean arterial pressure, a rise in cardiac output and plasma volume in association with an increase in renal plasma flow and glomerular filtration rate. The factors and the time course responsible for the initial hemodynamic changes seen in human pregnancy have not been completely documented. We hypothesize that systemic and renal hemodynamic changes occur early, prior to the presence of the fetal-placental unit. METHODS: Thirteen women were studied prior to and immediately following conception in identical fashion at gestational weeks 6, 8, 10, 12, 24 and 36. Individuals underwent mean arterial pressure, cardiac output, inulin and PAH clearance determinations. RESULTS: Mean arterial pressure decreased by six weeks gestation (mid follicular 81.5 +/- 2.6 vs. six weeks 68.7 +/- 2.0 mm tig, P < 0.001) in association with a significant increase in cardiac output, a decrease in systemic vascular resistance and an increase in plasma volume. Renal plasma flow and glomerular filtration rate increased by six weeks gestation. Plasma renin activity and aldosterone concentration increased significantly by six weeks, whereas norepinephrine levels did not change throughout pregnancy. Atrial natriuretic peptide levels increased later, at 12 weeks gestation. Plasma cGMP levels decreased and cGMP clearance increased by six and eight weeks, respectively. CONCLUSIONS: Peripheral vasodilation occurs early in pregnancy prior to full placentation in association with renal vasodilation and activation of the renin-angiotensin-aldosterone system. Plasma volume expansion occurs early, followed later by increases in ANP concentration, suggesting that ANP increases in response to changes in intravasular volume.

Adult↗

Effect of K+ATP channel inhibition on total and regional vascular resistance in guinea pig pregnancy.

Decreased vascular resistance and vasoconstrictor response during pregnancy enables an increase in cardiac output and regional blood flow to the uterine circulation. We sought to determine whether inhibition of vascular smooth muscle ATP-sensitive potassium (K+ATP) channel activity during pregnancy increased systemic and/or regional vascular resistance and resistance response to ANG II. A total of 32 catheterized, awake, pregnant or nonpregnant guinea pigs were treated with either the K+ATP channel inhibitor glibenclamide (3.5 mg/kg) or vehicle (DMSO) (n = 8/group). In nonpregnant and pregnant animals, glibenclamide raised blood pressure and systemic, uterine, and coronary vascular resistance, diminishing cardiac output and organ blood flow. Glibenclamide produced a greater rise in coronary vascular resistance in the pregnant than nonpregnant groups and increased renal and cerebral vascular resistance in the pregnant animals only. ANG II infusion raised blood pressure and systemic and renal vascular resistance and lowered cardiac output and renal blood flow in vehicle-treated animals. Glibenclamide augmented ANG II-induced systemic vasoconstriction in the nonpregnant and pregnant groups and the rise in uteroplacental vascular resistance in the pregnant animals. We concluded that K+ATP channel activity likely modulates systemic, uterine, and coronary vascular resistance and opposes ANG II-induced systemic vasoconstriction in nonpregnant and pregnant guinea pigs. Pregnancy augments K+ATP channel activity in the uterine, coronary, renal, and cerebral vascular beds and the uteroplacental circulation during ANG II infusion. Thus increased K+ATP channel activity appears to influence regional control of vascular resistance during guinea pig pregnancy but cannot account for the characteristic decrease in systemic vascular resistance and ANG II-induced systemic vasoconstrictor response.

Angiotensin II↗

Catecholamine response during 12 days of high-altitude exposure (4, 300 m) in women.

We have previously demonstrated that acclimatization to high altitude elicits increased sympathetic nerve activity in men. The purpose of this investigation was to determine 1) whether women respond in a similar manner as found previously in men and 2) the extent to which menstrual cycle phase influences this response. Sixteen eumenorrheic women (age, 23.6 +/- 1.2 yr; weight, 56.2 +/- 4. 3 kg) were studied at sea level and during 12 days of high-altitude exposure (4,300 m) in either their follicular (F; n = 11) or luteal (L; n = 5) phase. Twenty-four-hour urine samples were collected at sea level and during each day at altitude. Catecholamines were determined by high-performance liquid chromatography with electrochemical detection. Compared with sea-level values, urinary norepinephrine excretion increased significantly during altitude exposure, peaking on days 4-6. Thereafter, levels remained constant throughout the duration of altitude exposure. The magnitude of this increase was similar between the F (138%) and L (93%) phase. Urinary epinephrine levels were elevated on day 2 of altitude exposure compared with sea-level values for both F and L subjects (93%). Thereafter, urinary epinephrine excretion returned to sea-level values, and no differences were found between F and L subjects. Plasma catecholamine content was consistent with urinary values and supports the concept of an elevation in sympathetic activity over time at altitude. Mean and diastolic blood pressure as well as heart rate adjustments to high altitude correlated significantly with urinary norepinephrine excretion rates. It was concluded that 1) urinary and plasma catecholamine responses to 12 days of high-altitude exposure in women are similar to those previously documented to occur for men; 2) whereas no differences in catecholamine levels were observed between F- and L-phase assignments, for a given urinary norepinephrine excretion rate, blood pressure and heart rates were lower for F vs. L subjects; and 3) several cardiovascular adaptations associated with high-altitude exposure correlated with 24-h urinary norepinephrine excretion rates and thus sympathetic nerve activity.

Adrenal Glands↗

Women at altitude: changes in carbohydrate metabolism at 4,300-m elevation and across the menstrual cycle.

We hypothesized that, in women, the blood glucose response to a meal (BGR) would be lower after exposure to 4,300 m compared with sea level (SL) and that BGR would be reduced in the presence of estrogen plus progesterone (E+P) relative to estrogen alone (E). Sixteen women were studied in both the E and E+P conditions at SL and in either the E or E+P condition at 4,300 m. On day 9 in each condition, blood was sampled before, and every 30 min for 2 h after, the subjects ate a high-carbohydrate meal. At 4,300 m, BGR peaked at a lower value (5.73 +/- 0.94 mM) than at SL (6.44 +/- 1.45 mM) and returned to baseline more slowly (P < 0.05). Plasma insulin values were the same but C peptide was slightly higher at 4,300 m (P < 0. 05). At SL, BGR returned to baseline more slowly in E+P condition (5. 13 +/- 0.89 and 5.21 +/- 0.91 mM at 60 and 90 min, respectively) relative to E condition (4.51 +/- 0.52 and 4.69 +/- 0.88 mM, respectively) (P < 0.05). Insulin and C peptide were not different between E and E+P conditions. The data indicate that BGR is lower in women at high altitude compared with the SL, possibly due to greater suppression of hepatic glucose production or stimulation of peripheral glucose uptake by insulin. BGR was lower in E condition relative to E+P condition at SL and possibly at 4,300 m, but the relative concentrations of ovarian hormones do not appear to alter the magnitude of the change in BGR when women are exposed to high altitude.

Adult↗

Effects of pregnancy and chronic hypoxia on contractile responsiveness to alpha1-adrenergic stimulation.

Decreased contractile response to vasoconstrictors in uterine and nonuterine vessels contributes to increased blood flow to the uterine circulation during normal pregnancy. Pregnancies complicated by preeclampsia and/or chronic hypoxia show a reversal or diminution of these pregnancy-associated changes. We sought to determine whether chronic hypoxia opposes the reduction in contractile response in uterine and nonuterine vessels during normal pregnancy and, if so, whether decreased basal nitric oxide (NO) activity was involved. We examined the contractile response to phenylephrine (PE) in guinea pig uterine artery (UA), mesenteric artery (MA), and thoracic aorta (TA) rings isolated from nonpregnant or pregnant guinea pigs that had been exposed throughout gestation to either low (1,600 m, n = 47) or high (3,962 m, n = 43) altitude. In the UA, pregnancy reduced contractile sensitivity to PE and did so similarly at low and high altitude (EC50: 4.0 x 10(-8) nonpregnant, 9.3 x 10(-8) pregnant at low altitude; 4.8 x 10(-8) nonpregnant, 1.0 x10(-8) pregnant at high altitude; both P < 0.05). Addition of the NO synthase inhibitor nitro-L-arginine (NLA; 200 mM) to the vessel bath increased contractile sensitivity in the pregnant UA (P < 0.05) and eliminated the effect of pregnancy at both altitutes. NLA also raised contractile sensitivity in the nonpregnant high-altitude UA, but contractile response without NLA did not differ in the high- and low-altitude animals. In the MA, pregnancy decreased contractile sensitivity to PE at high altitude only, and this shift was reversed by NO inhibition. In the TA, neither pregnancy nor altitude affected contractile response, but NO inhibition raised contractile response in nonpregnant and pregnant TA at both altitudes. We concluded that pregnancy diminished contractile response to PE in the UA, likely as a result of increased NO activity, and that these changes were similar at low and high altitude. Counter to our hypothesis, chronic hypoxia did not diminish the pregnancy-associated reduction in contractile sensitivity to PE or inhibit basal NO activity in the UA; rather it enhanced, not diminished, basal NO activity in the nonpregnant UA and the pregnant MA.

Adrenergic alpha-Agonists↗

Follistatin has a biphasic response but follicle-stimulating hormone is unchanged during an inflammatory episode in growing lambs.

The effects on plasma follistatin concentrations of an inflammatory episode, induced by the intrathoracic injection of yeast, were examined in growing lambs; this model results in acute loss of appetite, food intake and liveweight and the activation of the acute-phase pathway for several weeks as adjudged by the production of haptoglobin and other acute-phase proteins. In these animals (n = 8) there was a biphasic response in follistatin concentrations, with an initial 200% increase (P < 0.001) in follistatin within 24 h of injection of yeast. Thereafter, follistatin concentrations were depressed to 70% of pretreatment levels 48 h after injection (P < 0.01), followed by a gradual recovery of concentrations to pretreatment values. In another group of lambs (n = 16) that were feed-restricted to mimic the reduced food intakes and liveweight changes in the yeast-injected group, plasma follistatin was also reduced to around 70% of pretreatment levels (P < 0.01) within 1 day of the dietary regimen being implemented, followed by a gradual return to pretreatment values as food intakes were increased. Plasma follistatin correlated significantly (r = 0.57, P < 0.0001) with food intake, but not with liveweight changes. Plasma follistatin concentrations were unchanged in a third group fed ad libitum (n = 8), except during two periods when food intakes were significantly (P < 0.05) reduced, when follistatin concentrations also decreased (P < 0.01). Plasma follicle-stimulating hormone (FSH) concentrations in the three groups of lambs were not significantly affected by the treatment regimes or changes in follistatin concentrations. These findings indicate that peripheral follistatin concentrations are modulated by both inflammatory and nutritional mechanisms, and that significant fluctuations in follistatin levels can occur without detectable perturbations in FSH secretion.

Animals↗

ECG observations in Tibetan and Han residents of Lhasa.

In order to compare the prevalence of electrocardiographic (ECG) abnormalities suggestive of right ventricular hypertrophy in native and immigrant populations residing at high altitude, a retrospective review was undertaken of data obtained from a random survey of healthy volunteers and persons with chronic mountain sickness (CMS). All persons included in the survey were ambulatory volunteers from the general community who were evaluated at the Tibet Institute of Medical Science in Lhasa, where the elevation is 3,658 meters. The 74 residents of Lhasa, whose ECGs were studied, included 30 healthy Tibetan natives of Lhasa; 24 healthy Han (Chinese) immigrants, born at or near sea level, who had migrated to high altitude as children or adults; and 20 persons with symptoms of CMS. The ECGs of all subjects were reviewed for predetermined criteria suggestive of right ventricular hypertrophy, which were found to be present in 17% of healthy Tibetan natives, 29% of healthy Han immigrants, and 50% of CMS patients. The Han subjects who had migrated as children presented evidence of right ventricular hypertrophy more commonly than did adult immigrants. The overwhelming majority (90%) of persons with CMS were Han. Thus, the frequency of ECG abnormalities consistent with right ventricular hypertrophy was similar in healthy young Tibetan and Han men, but these abnormalities were less common in Tibetan natives than in Han who had migrated to high altitude as children or in CMS patients. The prevalence of ECG evidence of right ventricular hypertrophy increased with duration of high altitude residence among Han.

Adult↗

Follicle-stimulating hormone in the brushtail possum (Trichosurus vulpecula): purification, characterization, and radioimmunoassay.

Follicle-stimulating hormone (FSH) was purified from brushtail possum (Trichosurus vulpecula) pituitary glands by using the following purification techniques: fractional ammonium sulfate precipitation, triazinyl-dye affinity chromatography, hydrophobic interaction chromatography, and gel filtration. A yield of 18 micrograms of FSH per gram of pituitary, with a recovery of 12%, was obtained from 1400 glands (20.3 g wet weight). The purified FSH activity per gram of protein was 1320 times more potent than the initial pituitary homogenate. Contamination with possum luteinizing hormone (LH) was < 0.02%. The amino acid composition of possum FSH was similar to that of ovine FSH. Amino-terminal sequencing for 11 cycles indicated that the alpha subunit has the same sequence as ovine FSH except for residue 7, where the possum FSH alpha subunit contains isoleucine compared to the ovine subunit which contains threonine. The beta subunit has two substitutions in the first 11 residues and does not contain the N terminal serine that is found in ovine FSH. Amino acid sequencing did not detect any contaminating proteins. Possum FSH bound possum and bovine testicular receptors with similar affinities. It was also able to stimulate in vitro cAMP production by Chinese hamster ovary cells which express recombinant FSH receptors. In the receptor assays and the bioassay possum FSH has about 21% of the potency of ovine FSH (USDA-oFSH-19-SIAFP-RP2). An RIA was developed for possum FSH using 125I-possum FSH and an antiserum raised against human FSH. The RIA has a sensitivity of 0.3 ng/ml, a 50% displacement of 2.7 ng/ml, and a cross reactivity of 0.05% against possum LH. Plasma FSH levels in male possums (10.4 +/- 2.4 ng/ml, n = 4) were higher (P < 0.05) than levels in females (1.0 +/- 0.1 ng/ml, n = 4). Five days after gonadectomizing these possums the plasma FSH levels increased (P < 0.05) to 27.1 +/- 0.2 ng/ml in the males and to 6.6 +/- 2.0 ng/ml in the females. In summary, we have purified and partially characterized possum FSH. We have also set up an RIA for the hormone and shown that males have higher levels than females and that plasma FSH increases after gonadectomy.

Amino Acid Sequence↗