Sage Journals: Discover world-class research

Abstract

Objective

Acclimatization to high altitude (HA) is accompanied by decrease in plasma atrial natriuretic peptide (ANP). On the other hand, circulating levels of the hormone are known to be influenced by age and ethnicity. The impact of these factors on ANP response during prolonged HA exposure remains unexplored. Hence, this study was conducted to examine possible age and ethnic variation in plasma proANP_1-98 levels in men after 3 to 4 weeks at HA.

Methods

Lowlanders (LL) were studied at sea level (SL) and after 3 to 4 weeks at an altitude of ∼4500 m. The LL group comprised Rajput (n = 48), Gorkha (n = 40), and South Indian (n = 43) ethnicities. Another group of HA natives (Ladakhi, n = 40) were studied at ∼4500 m only. Subjects were between 20 and 50 years of age. Estimation of plasma proANP_1-98 and biochemical, hematologic, and physiologic evaluation was done.

Results

In LL at HA, proANP_1-98 levels decreased (P < .001); plasma arginine vasopressin decreased (P < .05 in Rajputs and South Indians); and total protein, hemoglobin, and hematocrit increased (P < .05). Heart rate increased (P < .05), whereas arterial oxygen saturation decreased (P < .05) in all LL at HA. Ethnicity but not age variation in proANP_1-98 was observed under HA stress. In HA natives, plasma proANP_1-98 was higher than LL at HA and did not exhibit any age variation.

Conclusions

Plasma proANP_1-98 levels, reflecting medium-term ANP secretion, decrease during prolonged exposure to HA in LL. This is due to diuresis leading to plasma volume reduction that occurs during the acclimatization process. Ethnicity but not age variation is associated with plasma proANP_1-98 under HA stress.

Keywords

proatrial natriuretic peptide men chronic hypoxia high altitude

Introduction

Hypoxia is a known secretagogue for atrial natriuretic peptide (ANP) and enhances ANP gene expression in mammals.¹ Atrial natriuretic peptide is primarily secreted from atrial cardiomyocytes.² Cleavage of proANP (1-126), the predominant storage form of ANP in atrial granules, releases equimolar amounts of the biologically active peptide ANP (99-126) and proANP (1-98), the major circulating N-terminal ANP (proANP_1-98), into the circulation.³ For diagnostic accuracy and prognostic relevance, estimation of plasma proANP_1-98 has been suggested as a good reliable measure to measure of ANP as it is more stable ex vivo, has a longer plasma half-life, and, consequently, higher plasma concentrations (10 to 50 times) than ANP.² Hence, proANP_1-98 is more likely to reflect medium-term ANP secretion. Atrial natriuretic peptide release during hypoxia plays an important role in decreasing pulmonary arterial pressure (PAP), increasing fluid shift out of the circulation, and facilitating action of erythropoietin.⁴ However, subjects acclimating normally have little or no change in ANP, and it has been suggested that ANP may be triggered in pathologic conditions in which natriuresis is impaired.⁵^–7 In high altitude natives (HANs), Antezana et al⁸ have observed that plasma ANP level was less than that in sea level (SL) natives despite high PAP. However, ANP level in Ladakhis who are HANs of the Himalayas is not known, and it has been reported that pulmonary circulation in the Himalayan people is well adapted and better than that of the Andean people.⁹

Apart from various environmental and psychological factors, levels of plasma hormones are also influenced by age and exhibit ethnic variation. This may also affect the response to stress. The Framingham Study was the first to identify that plasma natriuretic peptide levels exhibit heritability and genetic linkage along with age variations in humans.¹⁰ Age-associated increase in plasma ANP and proANP_1-98 has been well documented.^2,10 Furthermore, aging-associated physiologic alterations in factors affecting ANP release such as PAP in hypoxia have been observed in both humans¹¹ and animals.¹² Some studies have reported the association between ANP gene polymorphisms and plasma ANP levels/proANP_1-98 levels, hypertension, cardiac hypertrophy, proteinuria, stroke, and recurrent stroke.^10,13 In this perspective, it is possible that variations in proANP_1-98 levels in men from different ethnic background across various age groups may be different under high altitude (HA) stress thereby modulating the adaptive processes. Also, studies concerning the influence of age on chronic hypoxia-induced structural and functional alterations in the cardiovascular system are very few and controversial.¹⁴ With respect to the Indian population, age and ethnic variations in proANP_1-98 levels under HA stress have not been studied previously. This population is characterized by high levels of endogamy and a high degree of genetic differentiation among various ethnic groups.¹⁵ The purpose of this report was to explore these issues by presenting data on morning plasma proANP_1-98 levels in lowlanders of different age groups and ethnicities at HA as compared with that at SL and to compare proANP_1-98 response in lowlanders with that of HANs at HA.

Materials and methods

Subjects

Healthy male subjects from the armed forces (n = 171) between 20 and 50 years of age were enrolled for the study after informed consent and approval from the ethics committee of the institute. Subjects were chosen from four ethnically distinct groups based on geographic zones and morphologic types¹⁶: Rajput, Gorkha, South Indian, and Ladakhi. Rajputs are from northwestern India (Rajasthan) with Caucasoid features; Gorkhas are basically from submountainous regions (2000 to 3000 m) from northern India with Mongoloid features, and they had been living at SL for ∼4 years prior to the study; and South Indians are people from the southern plains and coastal areas of the country with Australoid features. Ladakhis are HANs from Ladakh of the Himalayas, which is located with the Karakoram to the northwest, the Himalayas in the southwest, and the Trans-Himalayas at its core. High-altitude natives living at HA had never been to SL. The subjects of Rajput, Gorkha, and South Indian ethnicities are referred to as lowlanders. Subjects were categorically divided into 4 age groups (years): 20 to 24, 25 to 29, 30 to 34, and 35 to 50.

Study Protocol

All subjects of lowland origin were evaluated at SL. These subjects were inducted to an altitude of 3500 m where they stayed for 7 days. Then, they were inducted to a higher altitude: ∼4500 m for Rajputs and South Indians and ∼4400 m for Gorkhas, where they continued to stay. At this final altitude, the lowland subjects were evaluated after 3 to 4 weeks of stay. Another group of HANs were studied at ∼4500 m only.

Diet

Diet consisted of authorized rations of the Indian Army that included an average intake of 13 819 kJ (carbohydrate 61%, lipid 26%, protein 13%) at SL and 14 657 kJ (carbohydrate 60%, lipid 28%, protein 12%) for HA operations.¹⁷ Food was consumed at the common mess at respective locations and is essentially the same for all subjects. Salt content in the ration was 14 to 19g.¹⁸ There was no fluid restriction during the study.

Anthropometry

Body weight and height were measured using an electronic weighing machine (Delmer, India) and an anthropometer. Height was measured to the nearest 0.5 cm and weight to the nearest 0.5 kg. Body fat was estimated indirectly by calculating body mass index (BMI): body weight (kg) divided by the height squared (m²).

Sample Analysis

In all the subjects, fasting venous blood samples were collected between 0700 and 0800 hours. The subjects were rested for half an hour in a sitting position and then for 5 minutes in a supine position before blood drawing from the antecubital vein. Samples collected in ethylenediamine tetraacetic acid (EDTA) tubes were centrifuged, and plasma was stored at −80°C until analysis.

Biochemical Parameters

Plasma proANP_1-98 level (nmol/L) was measured by enzyme-immunoassay method (Biomedica Gruppe, Austria; code BI-20892). This kit is suitable for the use of EDTA plasma. It is recommended for stability of the peptide that sample storage be at −20°C or −70°C, and samples can be subjected to 4 freeze/thaw cycles without any loss of immune reactivity. The sensitivity of the assay was 0.050 nmol/L. The interassay and intra-assay coefficients of variation were 4% and 2%, respectively. The cross-reactivities with other natriuretic peptides were less than 1%.

Plasma arginine vasopressin (AVP) level (ng/mL) was measured by enzyme-immunoassay method (Phoneix Pharmaceuticals Inc., USA). The sensitivity of the assay was 0.06 ng/mL. The interassay and intra-assay coefficients of variation were <14% and <5%, respectively. Hormone estimations on all plasma samples were performed using the Molecular Devices VERSAmax Reader (Molecular Devices, USA). Plasma protein (g/dL) was measured by the Lowry method.¹⁹

Hematologic Parameters

Hemoglobin (g/dL) and hematocrit (%) was measured using the MS4 analyzer (Melet Schloesing, France).

Physiologic Parameters

Heart rate (HR; beats/minute) and arterial oxygen saturation by pulse oximetry (Spo₂; %) were measured by the Multi Parameter Patient Monitor (5553Pro; BPL, India).

Statistical Analysis

Data were analyzed by General Linear Model (GLM) repeated measure using SPSS software to see the change in proANP_1-98 level due to age (factor 1), ethnicity (factor 2), and repeated over altitude (ie, at SL and HA). To compare the three ethnicities (ie, lowlanders) with HANs (ie, Ladakhi) at HA for all age groups, GLM analysis was performed. Post hoc analysis was done using Student-Newman-Keuls test and Dunnett test for the two hypotheses, respectively. For other variables, data were analyzed using paired t test to compare SL with HA. P value less than .05 was considered significant. Values are expressed as mean ± SEM.

Results

The baseline characteristics of the study subjects are as shown in Table 1. At HA, body weight and BMI showed a significant decrease (P < .05) in lowland ethnicities compared with those at SL. There was no ethnic variation in BMI. In lowlanders, hemoglobin, hematocrit, and plasma protein showed a significant (P < .05) increase compared with those at SL. Plasma AVP showed a significant (P < .05) decrease in all lowland ethnic groups at HA. Significant (P < .05) changes in HR (increase) and Spo₂ (decrease) were observed in lowlanders at HA. These data are shown in Table 2. Observations on plasma proANP_1-98 levels are as follows (Table 3):

Sea level: Plasma proANP_1-98 levels in lowlanders were in the low normal range. Ethnicity (P < .001) but not age variation in plasma proANP_1-98 was observed among lowlanders. Plasma level in South Indians was higher than that in Rajputs and Gorkhas. There was no difference in plasma levels between Rajputs and Gorkhas.

High altitude: Changes observed in plasma proANP_1-98 in lowlanders were in the low normal range of SL values. In comparison with those at SL, plasma levels showed a significant (P < .001) decrease in all lowlanders. Reduction in plasma proANP_1-98 at HA was 86% in Rajputs, 83% in Gorkhas, and 60% in South Indians compared with that at SL. Similar to SL findings, ethnicity (P < .001) but not age variation in plasma proANP_1-98 was observed among lowlanders. Also, plasma levels in South Indians were significantly (P < .05) high among lowlanders, and there was no variation in plasma levels between Rajputs and Gorkhas.

Table 1

Characteristics of the study subjects

Variables	Lowlanders						HA native(HA only)
	Rajput		Gorkha		South Indian
	SL	HA	SL	HA	SL	HA
No. of subjects	48		40		43		40
Age (years)	31.4 ± 1.0		30.3 ± 0.9		30.8 ± 1.2		31.1 ± 1.2
Final altitude of study (m)	∼4500		∼4400		∼4500		∼4500
Barometric pressure (kPa)	60		62		60		60
Ambient temperature (°C)	−6 to 10		−6 to 10		3 to 22		3 to 22
Duration of stay at HA	22–28 days (mean 25 days)						Lifelong
Height (m)	1.74 ± 0.01		1.67 ± 0.01		1.72 ± 0.07		1.69 ± 0.01^bc
Weight (kg)	67.6 ± 1.1	64.8 ± 1.1^a	63.9 ± 1.2	61.9 ± 1.1^a	66.5 ± 1.0	64.9 ± 0.9^a	62.9 ± 1.3
BMI (kg/m²)	22.3 ± 0.3	21.3 ± 1.0^a	22.9 ± 0.4	22.2 ± 0.3^a	22.6 ± 0.3	22.1 ± 0.3^a	22.0 ± 0.4

Values are expressed as mean ± SEM. Level of significance: P < .05.

SL, sea level; HA, high altitude.

SL vs HA;

Rajput vs HA native;

South Indian vs HA native.

Table 2

Biochemical, hematologic, and physiologic characteristics for each ethnic group in subjects between 20 and 50 years of age

Variables	Lowlanders						HA native(HA only)
	Rajput		Gorkha		South Indian
	SL	HA	SL	HA	SL	HA
Plasma protein (g/dL)	7.2 ± 0.1	7.7 ± 0.1^a	7.6 ± 0.1	8.2 ± 0.1^a	7.7 ± 0.2	8.9 ± 0.1^a	8.0 ± 0.1^c
AVP (ng/mL)	3.6 ± 0.5	1.5 ± 0.2^a	0.8 ± 0.03	0.9 ± 0.2	24.5 ± 1.8	5.4 ± 0.3^a	0.2 ± 0.01^bc
Hb (g/dL)	14.2 ± 0.1	19.2 ± 0.1^a	13.2 ± 0.1	18.2 ± 0.2^a	13.7 ± 0.2	16.5 ± 0.3^a	17.6 ± 0.3^bd
Hct (%)	39.7 ± 0.4	50.4 ± 0.5^a	38.8 ± 0.4	54.7 ± 0.7^a	42.5 ± 0.5	51.5 ± 0.7^a	NA
SpO₂ (%)	98 ± 1.0	88.4 ± 0.2^a	97.4 ± 0.2	88.5 ± 0.5^a	96.9 ± 0.5	88.1 ± 0.4^a	87.6 ± 0.5
HR (beats/min)	64.1 ± 0.5	72.5 ± 1.5^a	63.6 ± 1.4	70.8 ± 1.5^a	61.9 ± 1.6	72.8 ± 1.9^a	67.7 ± 1.1^b

Values are expressed as mean ± SEM. Level of significance: P < .05.

AVP, arginine vasopressin; HA, high altitude; Hb, hemoglobin; Hct, hematocrit; SL, sea level; Spo₂, arterial oxygen saturation; HR, heart rate; NA, data not available.

SL vs HA;

Rajput vs HA native;

South Indian vs HA native;

Gorkha vs HA native.

Table 3

Plasma proANP_1-98 levels (nmol/L) in lowlanders and HA natives

Age group (years)	Lowlanders						HA natives(HA only)
	Rajput		Gorkha		South Indian
	SL	HA	SL	HA	SL	HA
20–24	0.65 ± 0.10	0.12 ± 0.04^a	0.53 ± 0.07	0.07 ± 0.02^a	1.84 ± 0.29^ce	0.75 ± 0.12^acd	0.76 ± 0.10^ef
20–24	n = 10		n = 8		n = 10		n = 11
25–29	0.75 ± 0.14	0.19 ± 0.04^a	0.52 ± 0.06	0.10 ± 0.03^a	1.18 ± 0.17^bce	0.48 ± 0.08^acd	1.15 ± 0.17^bce
25–29	n = 11		n = 10		n = 12		n = 10
30–34	0.72 ± 0.09	0.10 ± 0.03^a	0.50 ± 0.08	0.09 ± 0.02^a	1.63 ± 0.13^ce	0.58 ± 0.06^acd	1.16 ± 0.33^efg
30–34	n = 12		n = 11		n = 9		n = 7
35–50	0.67 ± 0.07	0.12 ± 0.03^a	0.66 ± 0.11	0.09 ± 0.02^a	1.57 ± 0.17^ce	0.77 ± 0.09^acd	1.33 ± 0.19^efg
35–50	n = 15		n = 11		n = 12		n = 12

Values are expressed as mean ± SEM. Level of significance: P < .05.

HA, high altitude; SL, sea level.

SL vs HA;

20–24 years vs 25–29 years;

Rajput vs South Indian;

Gorkha vs South Indian;

Rajput vs HA native;

Gorkha vs HA native;

South Indian vs HA native.

In HANs, plasma levels were within the SL normal range. Their values were intermediate between SL values of South Indians and those of North Indians (Rajputs and Gorkhas). proANP_1-98 levels in lowlanders at HA were significantly less than those in HANs. There was no age variation in HANs.

Discussion

To our knowledge, this study is the first to report on plasma proANP_1-98 level during prolonged HA exposure in relation to age and ethnicity with respect to the Indian population. The major findings of this study include decrease in proANP_1-98 levels in response to HA stress in lowlanders; variation in proANP_1-98 among different ethnic groups at HA; and absence of age-related variation in proANP_1-98 response to HA in lowlanders. In Ladakhis, who are HANs of the Himalayas, plasma proANP_1-98 level was within the SL normal range and did not exhibit age variation.

In lowlanders, plasma proANP_1-98 levels at SL were similar to the values reported in other populations using enzyme-linked immunosorbent assay (Biomedica Gruppe, Vienna, Austria).² Boomsma et al²⁰ have reported that a single blood sample, obtained after 30 minutes of quiet sitting as in our study, can give reliable and reproducible basal values. At SL, it can be observed that proANP_1-98 exhibits only ethnicity but not age variation. Such variation in physiologic concentrations of hormones involved in body fluid–electrolyte regulation in the Indian population has not been reported previously. In these individuals, BMI was within normal range, and there was no ethnic variation. Probably, the genetic expression of ANP differs among lowlanders. Although diet was similar in all the study subjects, it has been reported that dietary salt intake in urban southern India is higher than current recommendations for the general population.²¹ In the Framingham Study, it has been identified that 40% of the total variation in plasma natriuretic peptide levels is attributable to additive genetic effects in men.¹⁰

During HA exposure, changes in plasma proANP_1-98 in lowlanders was within the normal range. A uniform finding is that proANP_1-98 levels showed a decrease in all lowlanders irrespective of ethnicity. This is probably indicative of the fact that ANP secretion decreases after 3 to 4 weeks of stay at HA. It has been reported^22,23 that after 4 weeks of stay at HA, plasma ANP level decreases due to altitude diuresis. At this point, it can be observed that plasma AVP was also reduced in all subjects of lowland origin. Reduction in AVP at HA is known to promote diuresis and is a characteristic feature of acclimatized subjects.²⁴ In addition, the rise in plasma protein and hematocrit in lowlanders at HA is indicative of plasma volume contraction. Thus, diuresis resulting in depletion of total body water might have inhibited ANP release, which is reflected by a parallel decrease in plasma proANP_1-98 levels. Also, the trend of resting heart rate remaining slightly above pre-ascent values and decrease in plasma volume are suggestive of ongoing acclimatization processes in lowlanders at HA. Several other factors could also have contributed to the decrease in plasma proANP_1-98 in lowlanders at HA. During chronic HA exposure, decrease in ANP levels despite a sustained increase in PAP has been attributed to downregulation of hypoxia inducible factor-1α.⁷ Recently, it has been reported that plasma levels of N-terminal probrain natriuretic peptide, which is known to directly reflect right ventricular function and ANP, do not show any significant change despite an increase in pulmonary artery systolic pressure at HA.²⁵ Besides these factors, Spo₂ values above 85% in lowlanders at HA suggests that arterial hypoxemia was not severe enough to trigger ANP release.²⁶ Under HA stress, ethnicity but not age variation in plasma proANP_1-98 was observed among lowlanders. Although Rajputs and Gorkhas were studied in a relatively colder environment than that of South Indians at HA, it has been reported²⁷ that cold adaptability at HA was better only in Rajputs and Gorkhas than in South Indians. Also, it has been observed that ANP was normal in soldiers who stayed above 6000 m for >10 weeks at −30°C.²⁸ Differences in humoral response between blacks and whites after plasma volume contraction has been observed.²⁹ A similar phenomenon could have contributed to the difference observed between North Indians (Rajputs and Gorkhas) and South Indians at HA. This aspect needs further research in relation to other fluid regulatory hormones at HA. Plasma proANP_1-98 level in lowlanders was less than that of HANs at HA. Ramirez et al³⁰ have reported that HANs excrete a salt load with increased facility than do SL natives exposed to HA, but the factors mediating these mechanisms were found to be independent of hypoxemia-induced alterations of aldosterone or ANP.

In this study on Ladakhis, who are HANs of the Himalayas, plasma proANP_1-98 levels were between the SL values of South Indians and North Indians (Rajputs and Gorkhas). This finding requires further research with respect to the Indian population. Antezana et al⁸ have observed that plasma ANP levels in HANs were less than those in SL natives despite high PAP. Plasma proANP_1-98 levels in HANs of this study are higher than the ANP values reported for Han Chinese living at 4300 m for 14 years. This difference is probably due to the fact that Han Chinese are relative newcomers to HA. Hence the high circulating proANP_1-98 levels in Ladakhis may reflect an adaptational change through generations. Age-related variation in plasma proANP_1-98 in Ladakhis between 20 to 50 years of age was absent. This is an important observation as it is well known that the incidence of chronic mountain sickness increases with age, and the disease is associated with overproduction of ANP.¹²^,31,32 The hemoglobin value of <21.3³² in HANs of this study rules out excessive erythrocytosis.

In conclusion, HA stress is associated with significant reduction in plasma proANP_1-98 levels in lowlanders irrespective of age and ethnicity. This probably reflects a decrease in ANP release into the circulation during prolonged exposure to HA due to plasma volume contraction. Ethnicity but not age seems to influence proANP_1-98 levels at HA. In HANs, plasma proANP_1-98 was between the SL values of South Indians and North Indians (Rajputs and Gorkhas), did not exhibit age variation, and was higher than the plasma levels of lowlanders at HA. However, the results need to be interpreted with careful consideration of small sample size, lack of higher age groups, and lack of direct body-fluid and hemodynamic measurements.

Footnotes

Acknowledgments

The authors are grateful to the Director, Defence Institute of Physiology and Allied Sciences (DIPAS), Delhi, India, for providing necessary support and for a keen interest in this study. Technical support provided by Mr. Sanjeev Kumar, Tech Officer “A,” is gratefully acknowledged. Thanks are due to the soldiers who volunteered for the study and to the authorities of the Indian Army for logistic support for field study.

References

Chen

Y.F.

Atrial natriuretic peptide in hypoxia. Peptides 2005; 26, 1068–1077.

Clerico

Emdin

Diagnostic accuracy and prognostic relevance of the measurement of cardiac natriuretic peptides: a review. Clin Chem 2004; 50, 33–50.

Clerico

Fabio

A.R.

Passino

Emdin

Cardiac endocrine function is an essential component of the homeostatic regulation network: physiological and clinical implications. Am J Physiol 2006; 290, H17–H29.

Arjamaa

Nikinmaa

Natriuretic peptides in hormonal regulation of hypoxia responses. Am J Physiol 2009; 296, R257–R264.

Richalet

J.P.

The endocrine system. In: Hornbein

T.F.

Schoene

R.B.

eds. High Altitude: An Exploration of Human Adaptation , New York, NY: Marcel Dekker Inc, 2001, 601–644.

Espiner

E.A.

Nicholls

M.G.

Human atrial natriuretic peptide. Clin Endocrinol (Oxf) 1987; 26, 637–650.

Beidleman

B.A.

Staab

J.E.

Glickman

E.L.

Neurohormonal responses and adaptations during rest and exercise at altitude. In: Kramer

W.J.

Rogol

A.D.

eds. The Endocrine System in Sports and Medicine , Malden, MA: Blackwell Publishers, 2005, 453–454.

Antezana

A.M.

Richalet

J.P.

Noriega

Galarza

Antezana

Hormonal changes in normal and polycythemic high-altitude natives. J Appl Physiol 1995; 79, 795–800.

Anand

I.S.

Hypoxia and the pulmonary circulation. Thorax 1994; 49, S19–S24.

10.

Wang

T.J.

Larson

M.G.

Levy

et al. Heritability and genetic linkage of plasma natriuretic peptide levels. Circulation 2003; 108, 13–16.

11.

Rabinovitch

Gamble

W.J.

Miettinen

O.S.

Reid

Age and sex influence on pulmonary hypertension of chronic hypoxia and on recovery. Am J Physiol 1981; 240, H62–H72.

12.

Rhodes

Comparative physiology of hypoxic pulmonary hypertension: historical clues from brisket disease. J Appl Physiol 2005; 98, 1092–1100.

13.

London

Natriuretic peptides and cardiac hypertrophy. J Am Coll Cardiol 2006; 48, 506–507.

14.

Ostadal

Ostadalova

Dhalla

Development of cardiac sensitivity to oxygen deficiency: comparative and ontogenic aspects. Physiol Rev 1999; 79, 635–659.

15.

Indian Genome Variation Consortium

Genetic landscape of the people of India: a canvas for disease gene exploration. J Genet 2008; 87, 3–20.

16.

Indian Genome Variation Consortium

The Indian genome variation database (IGVdb): a project overview. Hum Genet 2005; 118, 1–11.

17.

Babusha

S.T.

Singh

V.K.

Shukla

Singh

S.N.

Prasad

N.N.

Assessment of ration scales of the armed forces personnel in meeting the nutritional needs at plains and high altitudes-I. Def Sci J 2008; 58, 734–744.

18.

Malhotra

M.S.

Chandra

Rai

R.M.

Venkataswamy

Sridharan

Food intake and energy expenditure of Indian troops in training. Br J Nutr 1976; 35, 229–244.

19.

Waterborg

J.H.

Mathews

J.H.

The Lowry method for protein quantitation. In: Walker

J.M.

ed. Basic Protein and Peptide Protocols , Totowa, NJ: Humana Press Inc, 1994, 1–4.

20.

Boomsma

Deinum

Van den Meiracker

A.H.

Relationship between natriuretic peptide concentrations in plasma and posture during blood sampling. Clin Chem 2001; 47, 963–965.

21.

Radhika

Sathya

R.M.

Sudha

Ganesan

Mohan

Dietary salt intake and hypertension in an urban south Indian population – [CURES – 53]. JAPI 2007; 55, 405–411.

22.

Ponchia

Noventa

Zaccaria

et al. Body fluids, atrial volumes, and atrial natriuretic peptide during and after high-altitude exposure. Wilderness Environ Med 1995; 6, 11–19.

23.

Zaccaria

Rocco

Noventa

Varnier

Opocher

Sodium regulating hormones at high altitude: basal and post-exercise levels. J Clin Endocrinol Metab 1998; 83, 570–574.

24.

Singh

Khanna

P.K.

Srivastava

M.C.

Lal

Roy

S.B.

Subramanian

C.S.

Acute mountain sickness. New Engl J Med 1969; 280, 175–184.

25.

Toshner

M.R.

Thompson

A.A.R.

Irving

J.B.

Baillie

J.K.

Morton

J.J.

Peacock

A.J.

NT-proBNP does not rise on acute ascent to high altitude. High Alt Med Biol 2008; 9, 307–310.

26.

Kawashima

Kubo

Hirai

Yoshikawa

Matsuzawa

Kobayashi

Plasma levels of atrial natriuretic peptide under acute hypoxia in normal subjects. Respir Physiol 1989; 76, 79–92.

27.

Mathew

Purkayastha

S.S.

Nayar

H.S.

Variation in the susceptibility to cold injury in Indians. Int J Biometeorol 1979; 23, 263–270.

28.

Anand

I.S.

Chanadrashekhar

Rao

S.K.

et al. Body fluid compartments, renal blood flow, and hormones at 6,000m in normal subjects. J Appl Physiol 1993; 74, 1234–1239.

29.

Luft

F.C.

Grim

C.E.

Fineberg

Weinberger

M.C.

Effects of volume expansion and contraction in normotensive whites, blacks, and subjects of different ages. Circulation 1979; 59, 643–650.

30.

Ramirez

Bittle

P.A.

Agosti

S.J.

Dietz

Colice

G.L.

Salt loading test in a population adapted to moderately high altitude living (3,000 m). Aviat Space Environ Med 1993; 64, 831–838.

31.

R.L.

Shai

H.R.

Takeoka

et al. Atrial natriuretic peptide and red cell 2,3-diphosphoglycerate in patients with chronic mountain sickness. Wilderness Environ Med 2001; 12, 2–7.

32.

Penaloza

Arias-Stella

The heart and pulmonary circulation at high altitudes: healthy highlanders and chronic mountain sickness. Circulation 2007; 115, 1132–1146.

Plasma proANP 1-98 Response During High Altitude Stress: Effect of Age and Ethnicity

Abstract

Objective

Methods

Results

Conclusions

Keywords

Introduction

Materials and methods

Subjects

Study Protocol

Diet

Anthropometry

Sample Analysis

Biochemical Parameters

Hematologic Parameters

Physiologic Parameters

Statistical Analysis

Results

Discussion

Footnotes

Acknowledgments

References