Association of high-altitude systemic hypertension with the deletion allele-of the angiotensin-converting enzyme (ACE) gene

Kumar, Ratan; Pasha, M. A. Qadar; Khan, Amjad P.; Gupta, Vikas; Grover, S. K.; Norboo, Tsering; Srivastava, Kamna; Selvamurthy, W.; Brahamchari, S. K.

doi:10.1007/s00484-003-0172-4

Cited by 29 publications

(18 citation statements)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…37 In contrast, short visits to modest or high altitudes induce significant increases in systemic blood pressure, 38 and preexisting genetic factors may predispose low altitude residents to altitude-induced hypertension. 39 Our data suggest that the Ahr may represent a candidate gene for altitude-induced hypertension. Further study of AHR KO mice may reveal novel pathways in the regulation of systemic blood pressure by hypoxia and identify physiological mechanisms that contribute to altitude-induced systemic hypertension.…”

Section: Perspectivesmentioning

confidence: 68%

Loss of the Aryl Hydrocarbon Receptor Induces Hypoxemia, Endothelin-1, and Systemic Hypertension at Modest Altitude

et al. 2008

View full text Add to dashboard Cite

Abstract-The aryl hydrocarbon receptor (AHR) is a basic helix-loop-helix Per-Arnt-Sim transcription factor that mediates induction of metabolic enzymes and toxicity of certain environmental pollutants. Although AHR knockout (KO) mice develop cardiac hypertrophy, conflicting reports associate this pathology with hypotension or endothelin (ET)-1-dependent hypertension. Because hypertension occurred at modest altitude, we tested the hypothesis that loss of AHR increases the sensitivity to hypoxia-induced ET-1, contributing to systemic hypertension. We found that AHR KO mice were hypertensive at modest altitude (1632 m) but hypotensive at low altitude (225 m). When AHR KO mice residing at 1632 m were exposed to the partial pressure of inspired oxygen (PIO 2 ) at sea level for 11 days, blood pressure declined to levels measured at 225 m. Although plasma ET-1 in AHR KO mice was significantly elevated at 1632 m and decreased at 225 m and sea level PIO 2 , pulmonary prepro-ET-1 mRNA was significantly reduced at 1632 m and decreased further at 225 m and sea level PIO 2 . Blood gas analysis revealed that AHR KO mice were hypoxemic, hypercapnic, and acidotic at 1632 m, values that were attenuated and normalized after 24 hours and 11 days under sea level PIO 2 , respectively. Lastly, AHR inactivation in endothelial cells by small interfering RNA significantly reduced basal prepro-ET-1 mRNA but did not alter hypoxia-induced expression. Our studies establish the AHR KO mouse as a model in which modest decreases in PIO 2 lead to hypoxemia, increased plasma ET-1, and systemic hypertension without increased pulmonary prepro-ET-1 mRNA expression. Key Words: blood pressure Ⅲ hypertension Ⅲ endothelin Ⅲ oxygen Ⅲ gene regulation T he aryl hydrocarbon receptor (AHR) is a ligand-activated transcription factor belonging to the basic helix-loophelix Per-Arnt-Sim family of DNA binding proteins, which also includes hypoxia-inducible factors. 1 Although the AHR is known to mediate induction of drug-metabolizing enzymes and toxicity after exposure to 2,3,7,8-tetrachlorodibenzo-pdioxin, recent evidence has revealed a physiological role for AHR in cardiovascular homeostasis. AHR knockout (KO) mice develop cardiac hypertrophy, 2,3 which is mediated, in part, by elevated plasma angiotensin II and endothelin-1 (ET-1). 4,5 There are conflicting reports, however, of whether the cardiac hypertrophy is associated with systemic hypertension. Lund et al 4,5 reported that cardiac hypertrophy in AHR KO mice is preceded by hypertension, whereas Vasquez et al 6 and Ichihara et al 7 reported that AHR KO mice are hypotensive and normotensive, respectively. The explanation for the disparate blood pressure values among these studies is unclear.AHR and hypoxia-inducible factor-1␣ share a common dimerization partner, AHR nuclear translocator (hypoxiainducible factor-1␤), as well as other transactivators, and studies have shown that these 2 signal transduction pathways can exhibit reciprocal inhibitory cross-talk. 8,9 The mechanism by which this functional inter...

show abstract

Section: Perspectivesmentioning

confidence: 68%

Loss of the Aryl Hydrocarbon Receptor Induces Hypoxemia, Endothelin-1, and Systemic Hypertension at Modest Altitude

et al. 2008

View full text Add to dashboard Cite

show abstract

“…This difference may result in an exaggerated increase in systolic and diastolic BP with age, as well as with a higher diastolic BP at rest, compared to Japanese people [3]. Fifth, angiotensin-converting-enzyme gene I/D polymorphism is reportedly associated with highaltitude disorders as well as with differences in physical performance [4][5][6]. It is also speculated that this polymorphism may be related to the larger increase in BP with age observed herein.…”

Section: Discussionmentioning

confidence: 89%

Effect of aging on blood pressure in Leh, Ladakh, a high-altitude (3524 m) community, by comparison with a Japanese town

Otsuka

Norboo²,

Otsuka

et al. 2005

Biomedicine & Pharmacotherapy

Self Cite

View full text Add to dashboard Cite

The effect of aging on blood pressure (BP) and heart rate (HR) was investigated in a cross-sectional study in the high-altitude community of Leh, Ladakh (altitude: 3524 m) and a Japanese community in U town, Hokkaido (altitude: 25 m). BP and HR were obtained in a sitting position from 332 subjects 13-81 years of age in Ladakh, and from 216 Japanese citizens, 24-79 years of age. Measurements were taken after a 2-min rest, using a semi-automated BP device (UA-767 PC, A&D Co. LTD, Tokyo). High-altitude people showed higher diastolic BP and HR values than lowland people (83.2 vs. 76.9 mmHg and 78.6 vs. 69.2 bpm, P < 0.001), but no difference in systolic BP. Highland people also showed a steeper BP increase with age than the lowland people (systolic BP: 0.7476 vs. 0.3179 mmHg/year, P < 0.0005; diastolic BP: 0.3196 vs. 0.0750 mmHg/year, P < 0.001). This chronoecologic investigation in Ladakh examined the circulation as a physiological system at highaltitude. Our data indicate the need for a more comprehensive cardiovascular assessment for a better diagnosis and a more fruitful treatment. Longitudinal observations of effects of socio-ecologic factors on the cardiovascular system should help prevent strokes and other cardiovascular events, especially at high altitude.

show abstract

“…The involvement of the renin-angiotensin-aldosterone system (RAAS) in the control of the salt and water balance and thereby blood pressure is well known during hypoxia and high altitude exposure [35,36]. At high altitude renal secretion is stimulated by decreased renal blood flow [37], which in turn activates the RAAS [16].…”

Section: Discussionmentioning

confidence: 99%

“…High-altitude environments imply stress factors: hypoxia, cold, humidity, solar radiation, cosmic radiation and isolation, causing many physiological and biochemical changes in body, including structural changes in the walls of small pulmonary arteries, predominantly increased masculinization, increased pulmonary vascular resistance and sustained elevation of pulmonary arterial pressure, instigating high altitude pulmonary hypertension (HAPH) [15][16][17][18]. In humans, large inter-individual differences exist in the magnitude of the pulmonary pressure response to hypoxia [19][20][21][22], with some subjects demonstrating exaggerated increases in pulmonary arterial pressure [23,24].…”

Section: Introductionmentioning

confidence: 99%

Association of High Altitude Hypertension with Angiotensin Converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism

Ch¹,

Doza²,

Kumar³

2017

UNOAJ

View full text Add to dashboard Cite

The study included ACE gene I/D polymorphism and its association between high altitude hypertension. Genetic, biochemical, anthropometric and Physiometeric results were analyzed using statistical software. The results were non-significant for I/D polymorphism.Objective: ACE is the major enzyme of hypertension and with most commonly reviewed I/D polymorphism. High-altitude exposes various physiological and biochemical changes, which contributes a rise in systemic blood pressure of the body. There are very few studies available in North-India, with a core focus on the high altitude hypertension. Therefore, a current study supported an interest to find out the association of high altitude hypertension with ACE gene I/D polymorphism.Methods: to study the significant association with respect to altitude, genetic, biochemical, anthropometric and physio-metric comparison were conducted among 98 individuals where 489nbeing hypertensive patients and other half being normotensive, inclusive of both males and females. The entire results were finally examined and analyzed using statistical software SPSS 16.0 version. Results:According to study results, mean arterial blood pressure and triglycerides were significantly (p<0.05) associated with SBP among both hypertensive and normotensives. Whereas HDL, LDL-HDL ratio, CHO-HDL were significantly associated only among hypertensive, and age, PP, and SpO2 have been significantly (p<0.05) associated with SBP among normotensive, a strong predictor for SBP. Conclusion:The genotypic observations were visibly linked with the disease, however, the results were statistically non-significant (ID/DD vs. II; OR: 0.54, 95% CI: 0.20-1.44, p= 0.217). A further study with considerate knowledge of noteworthy dynamics, mainly, altitude, population size, and ethnicity are recommended.

show abstract

Association of high-altitude systemic hypertension with the deletion allele-of the angiotensin-converting enzyme (ACE) gene

Cited by 29 publications

References 15 publications

Loss of the Aryl Hydrocarbon Receptor Induces Hypoxemia, Endothelin-1, and Systemic Hypertension at Modest Altitude

Loss of the Aryl Hydrocarbon Receptor Induces Hypoxemia, Endothelin-1, and Systemic Hypertension at Modest Altitude

Effect of aging on blood pressure in Leh, Ladakh, a high-altitude (3524 m) community, by comparison with a Japanese town

Association of High Altitude Hypertension with Angiotensin Converting Enzyme (ACE) Gene Insertion/Deletion Polymorphism

Contact Info

Product

Resources

About