Effect of Pressure Overload on Angiotensin Receptor Expression in the Rat Heart During Early Postnatal Life

Oliviéro, P.; Chassagne, Catherine; Kolář, František; Adamy, C.; Marotte, F.; Samuel, Jane‐Lise; Rappaport, L.; Ošťádal, B

doi:10.1006/jmcc.2000.1198

Cited by 14 publications

(8 citation statements)

References 33 publications

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“…The amplification reaction was performed with 5 units of Taq DNA polymerase (Life Technologies) in 100 l of an aqueous mixture containing 300 ng of each of AT1 or AT2 sense and antisense primers, 0.2 nM dNTP-Na salts, 2 mM MgCl2, and 10 of PCR buffer (ϫ10). Thirty-one amplification cycles were performed in a Perkin-Elmer apparatus, and signals of PCR products were analyzed on ethidium bromide-stained gels using densitometry with a computer-based imaging system (Gel Doc 1000, Bio-Rad), as previously described (28).…”

Section: Methodsmentioning

confidence: 99%

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: Methodsmentioning

confidence: 99%

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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“…10 Binding analysis of angiotensin II (Ang II) receptors was performed as described previously. 17 AT-receptor subtypes were identified by incubation with losartan or PD 123319.…”

Section: Collagen and Angiotensin II Receptor Assaymentioning

confidence: 99%

Cardiac Specific Increase in Aldosterone Production Induces Coronary Dysfunction in Aldosterone Synthase–Transgenic Mice

et al. 2004

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Background-Elevated circulating aldosterone level is associated with impaired cardiovascular function. Although the mechanisms are not fully understood, aldosterone antagonists decrease total and cardiovascular mortality in heart failure and myocardial infarction. Aldosterone induces cardiac fibrosis in experimental models, and it is synthesized locally in rat heart. These observations suggest pathological effects of aldosterone in heart that remain unclear. Methods and Results-Transgenic mice (TG) that overexpress the terminal enzyme of aldosterone biosynthesis, aldosterone synthase (AS), in heart have been raised by gene targeting with the ␣-myosin heavy chain promoter. AS mRNA increased 100-fold and aldosterone concentration 1.7-fold in hearts of male TG mice relative to wild-type. No structural or myocardial alterations were evidenced, because ventricle/body weight, AT 1 and AT 2 receptor binding, and collagen content were unchanged in TG. No alteration in cardiac function was evidenced by echocardiography, isolated perfused heart, or whole-cell patch clamp experiments. In contrast, coronary function was impaired, because basal coronary flow was decreased in isolated perfused heart (Ϫ55% of baseline values), and vasodilatation to acetylcholine, bradykinin, and sodium nitroprusside was decreased by 75%, 60%, and 75%, respectively, in TG mice compared with wild-type, showing that the defect was not related to NO production. Conclusions-Increased cardiac aldosterone production in male mice induces a major coronary endothelium-independent dysfunction with no detectable alterations in cardiac structure and function. However, coronary dysfunction may be harmful for coronary adaptation to increased flow demand.

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“…AT 1 (20). We analyzed the AT 1 and AT 2 binding capacities in the rat heart exposed to hypoxia with or without irbesartan treatment.…”

Section: Resultsmentioning

confidence: 99%

“…The occurence of AT 2 receptors in the neonatal myocardium is higher than in adulthood (20), and AT 2 signaling pathway could be "unmasked" because of higher availability of ANG II when AT 1 receptors are blocked. Moreover, the antiangiogenic effect of AT 2 stimulation has been postulated in several studies (5,6,19,36).…”

Section: Discussionmentioning

confidence: 99%

ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats

Rakusan¹,

Chvojkova²,

Oliviéro³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Rakusan K, Chvojkova Z, Oliviero P, Ostadalova I, Kolar F, Chassagne C, Samuel JL, Ostadal B. ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats. Am J Physiol Heart Circ Physiol 292: H1237-H1244, 2007. First published December 1, 2006; doi:10.1152/ajpheart.00965.2006.-Chronic hypoxia has been shown to stimulate myocardial microvascular growth and improve cardiac ischemic tolerance in young and adult rats. The aim of this study was to determine whether the ANG II type 1 receptor (AT1) pathway was involved in these processes. Newborn Wistar rats, exposed to chronic intermittent hypoxia (8 h/day) for 10 days, were simultaneously treated with AT1 receptor blocker irbesartan and compared with untreated animals. The major finding is that chronic hypoxia increased the capillary supply of myocardial tissue, which was even more pronounced in hypertrophied right ventricle, whereas increased arteriolar supply was found only in the left ventricle. This angiogenic response was completely prevented by irbesartan. Moreover, chronic hypoxia improved the postischemic recovery of cardiac contractile function during reperfusion, and this protective effect was also completely abolished by irbesartan. Chronic hypoxia increased the myocardial density of AT1 but not of ANG II type 2 receptor subtypes, whereas the effect of irbesartan was not significant. The expression of caveolin-1␣ markedly increased in response to chronic hypoxia, and irbesartan prevented this effect. Neither hypoxia nor irbesartan treatment altered the expression of nitric oxide synthase 3, heat shock protein 90, and VEGF. It is concluded that the AT1 receptor pathway plays an important role in coronary angiogenesis and improved cardiac ischemic tolerance induced in neonatal rats by chronic hypoxia.angiotensin II receptors; ischemia-reperfusion; caveolin-1 ADAPTATION TO CHRONIC HYPOXIA increases cardiac tolerance to all major deleterious consequences of acute oxygen deprivation in both adult and immature heart. In addition to the protective effect, chronic hypoxia may also induce other adaptive responses, including hypoxic pulmonary hypertension and right ventricular (RV) hypertrophy (22). This is a beneficial adaptation, allowing the RV to cope with an increased afterload and to maintain cardiac output. Although many potential factors have been proposed to play a role in the mechanisms of cardiac adaptation to chronic hypoxia, the available data are not sufficiently conclusive. Moreover, a substantial amount of information concerning the adaptive response was obtained from the adult myocardium, whereas much less is known about this process in the immature heart. However, clinical relevance of the developmental approach is obvious: chronic hypoxia is the main pathophysiological feature of hypoxemic congenital heart disease. Understanding the mechanisms by which these malformations modify the myocardium and how they impact on the adaptive mechanisms during ischemia may provide ins...

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Effect of Pressure Overload on Angiotensin Receptor Expression in the Rat Heart During Early Postnatal Life

Cited by 14 publications

References 33 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

Cardiac Specific Increase in Aldosterone Production Induces Coronary Dysfunction in Aldosterone Synthase–Transgenic Mice

ANG II type 1 receptor antagonist irbesartan inhibits coronary angiogenesis stimulated by chronic intermittent hypoxia in neonatal rats

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