Chronic hypoxia upregulates the expression and function of AT(1) receptor in rat carotid body

Leung, Po Sing; Sy, Lam; Fung, ML

doi:10.1677/joe.0.1670517

Cited by 78 publications

(87 citation statements)

References 29 publications

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“…Accounting that, the simultaneous accumulation of AT 1 mRNA and AT 1 receptors indicates that hypoxia-induced transcriptional mechanisms may activate the AT 1 gene via a hypoxia-response DNA element. This hypothesis is supported by previous reports of an activation of the AT 1 gene in the rat aorta under hypoxic condition (16) and the presence in the AT 1 gene promoter of an AP1 response element (12) that would respond to hypoxia (40). Regarding AT 2 , our finding of ventricular changes during the late stage of hypoxia, but not in the MCTtreated rat, suggests that AT 2 expression regulation might be associated with hypoxia-rather than overload-induced responses.…”

Section: Discussionsupporting

confidence: 82%

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

Adamy

Oliviéro

Eddahibi

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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. Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension. Am J Physiol Heart Circ Physiol 283: H733-H740, 2002. First published April 18, 2002 10.1152/ ajpheart.01088.2001.-Right ventricular myocardial hypertrophy during hypoxic pulmonary hypertension is associated with local renin-angiotensin system activation. The expression of angiotensin II type 1 (AT 1) and type 2 (AT2) receptors in this setting has never been investigated. We have therefore examined the chronic hypoxia pattern of AT 1 and AT2 expression in the right and left cardiac ventricles, using in situ binding and RT-PCR assays. Hypoxia produced right, but not left, ventricular hypertrophy after 7, 14, and 21 days, respectively. Hypoxia for 2 days was associated in each ventricle with a simultaneous and transient increase (P Ͻ 0.05) in AT1 binding and AT1 mRNA levels in the absence of any significant change in AT 2 expression level. Only after 14 days of hypoxia, AT 2 binding increased (P Ͻ 0.05) in the two ventricles, concomitantly with a right ventricular decrease (P Ͻ 0.05) in AT 2 mRNA. Along these data, AT1 and AT2 binding remained unchanged in both the left and hypertrophied right ventricles from rats treated with monocrotaline for 30 days. These results indicate that chronic hypoxia induces modulations of AT1 and AT2 receptors in both cardiac ventricles probably through direct and indirect mechanisms, respectively, which modulations may participate in myogenic (at the level of smooth or striated myocytes) rather than in the growth response of the heart to hypoxia. chronic hypoxia; heart ventricles; angiotensin II; AT1 and AT 2 receptor subtypes CHRONIC HYPOXIA-INDUCED pulmonary hypertension is characterized by an increased pulmonary vascular resistance due to pulmonary artery thickening that impedes ejection of blood by the cardiac right ventricle (RV) and leads to RV hypertrophy (1,20,21,33). Evidence that chronic hypoxia increases the plasma levels of renin (9), angiotensin-converting enzyme (ACE) (24), and angiotensin II (ANG II) (42) has stimulated interest in the contribution of the renin-angiotensin system to the hypoxia-induced cardiopulmonary changes. This hypothesis is supported by data from chronically hypoxic rats showing that ACE inhibitor treatment reduces pulmonary arterial pressure (5,14,26,27,34,41), pulmonary artery thickening (5, 26, 27, 41), and RV hypertrophy (14,26,32,41).Two pharmacologically distinct subtypes of receptors, designated as AT 1 and AT 2 , participate in regulating ANG II activity. Both have been described based on their affinity for selective receptor antagonists and their sensitivity to reducing agents (6). Whereas AT 1 mediates the vasoconstrictor and growth-promoting effects of ANG II, AT 2 has been suggested to mediate vasodilator effects and to exert antigrowth action within many cell types, including vascular smooth muscle cells, endothelial cells, cardiac fibroblasts, and myocytes (6,12,22,23). We have shown in the rat hypoxic lung that AT 1 and AT 2 receptor e...

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Section: Discussionsupporting

confidence: 82%

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

Adamy

Oliviéro

Eddahibi

et al. 2002

American Journal of Physiology-Heart and Circulatory Physiology

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“…Within the carotid body itself, responses to hypoxia are mediated by glomus type-I cells [20], which are known to express AT1 receptors [13]. The expression of these receptors is increased as part of the adaptive process to chronic hypoxia [12], consistent with the suggestion that local chemoreceptor RAS may play a role in mediating hypoxic ventilatory responses. However, the role of such glomus AT1 receptors in the transduction of responses to acute hypoxic exercise remain to be elucidated.…”

Section: Discussionsupporting

confidence: 64%

“…At altitude, diminished alveolar oxygen tensions lead to lower arterial oxygen tensions. However, the fall in oxygen availability with altitude is sensed by carotid bodies that contain hypoxia-sensitive AngII type-1 (AT1) receptors [12,13], driving an increase in minute ventilation (V9E). This compensatory increase in alveolar ventilation (the hypoxic ventilatory response; HVR), helps sustain arterial oxygen saturations (Sa,O 2 ) and tissue oxygen delivery.…”

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confidence: 99%

Angiotensin-converting enzyme genotype and the ventilatory responseto exertional hypoxia

Patel

Woods²,

MacLeod³

et al. 2003

Eur Respir J

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The “insertion” (I) rather than “deletion” (D) variant of the human angiotensin-converting enzyme (ACE) gene is associated with both lower tissue ACE activity and elite performance at high altitude. Three genotypes, II, ID and DD, are thus represented in the population. The authors examined whether an improved ventilatory response to hypoxic exercise may contribute to this effect.Subjects (n=60; 37 male, mean±sem age 23.6±0.6 yrs, 14 II, 30 ID, 16 DD) underwent incremental cardiopulmonary exercise testing to establish maximal oxygen uptake and ventilatory threshold (VT). Four hours later, subjects exercised for 6 mins at 50% of the workload at VT. The protocol was repeated 15 mins later while breathing 12.5±0.5% oxygen in nitrogen.All subject characteristics were independent of genotype, as were data during normoxic exercise. However, the hypoxia-induced rise in minute ventilation was significantly greater among those of II genotype (39.6±4.1%versus27.9±2.0%versus28.4±2.2% for IIversusIDversusDD, respectively). These data are supported by a significantly greater decrease in end tidal carbon dioxide (consistent with an increase in alveolar ventilation) among those homozygous for the I allele (II −18.7±1.3%, ID −15.7±0.4%, DD −15.1%±1.1).The ventilatory response to hypoxic exercise is influenced by angiotensin-converting enzyme genotype. Potential implications concern high altitude performance and the pathogenesis and management of hypoxic lung disease.

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“…Hypoxic stress is known to be one such factor which may lead to changes of tissue RAS expression in, for example, the kidney (Neylon et al 1996), the lung (Morrell et al 1995), the carotid body (Leung et al 2000b), the epididymis (Leung et al 2001) and the heart (Morrell et al 1997). These data suggest that tissue RAS is differentially affected by hypoxia and is intimately involved in both the physiology and pathophysiology of the respective tissues.…”

Section: Regulation Of Pancreatic Tissue Ras By Chronic Hypoxiamentioning

confidence: 99%

Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas

Leung

Carlsson²

2001

Journal of Molecular Endocrinology

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117

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The classical concept of the renin-angiotensin system (RAS) is that of a blood-borne cascade, whose final and bioactive product, angiotensin II, plays an important endocrine role in the maintenance of blood pressure and electrolyte as well as fluid balance. In addition to this circulating RAS, there are an increasing number of studies to suggest the existence of a local angiotensin-generating system in several tissues. The so-called tissue RAS can act locally as a paracrine and/or autocrine factor in meeting specific needs for individual tissues and it can operate, in whole or in part, independently of the circulating counterpart. Recent studies on the expression and localization of key RAS components, particularly angiotensinogen and renin, have provided solid evidence for the existence of an intrinsic, angiotensin-generating system in the pancreas. The tissue RAS has a potential role in finely regulating exocrine and endocrine functions of the pancreas such as ductal anion secretion and islet hormonal secretion. Some of these effects may be exerted via the markedly vasoconstrictive effects of RAS. Of particular interest in this context are the recent epidemiological data showing that administration of angiotensin-converting enzyme inhibitors appears to be protective against the development of diabetes in hypertensive patients. Moreover, the upregulation of pancreatic RAS has been shown to occur during chronic hypoxia. The significance of changes in pancreatic RAS could have a potential role in acute pancreatitis, islet transplantation and in different shock states, by causing a further decrease of blood perfusion in the pancreas.

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Chronic hypoxia upregulates the expression and function of AT(1) receptor in rat carotid body

Cited by 78 publications

References 29 publications

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

Cardiac modulations of ANG II receptor expression in rats with hypoxic pulmonary hypertension

Angiotensin-converting enzyme genotype and the ventilatory responseto exertional hypoxia

Tissue renin-angiotensin system: its expression, localization, regulation and potential role in the pancreas

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