Physiopathogenesis of acute aortic coarctation hypertension in conscious rats.

Salgado, Hélio César; Skelton, M. M.; Salgado, Maria Cristina O.; Cowley, Allen W.

doi:10.1161/01.hyp.23.1_suppl.i78

Cited by 26 publications

(18 citation statements)

References 19 publications

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“…Pathological conditions resulting in increased cardiac workload generally are associated with activation of systemic and local renin-angiotensin systems and increased levels of circulating angiotensin II (AngII) (1,2). However, little is understood about how AngII type 1a receptors (AT 1a R) are modulated under these same pathological conditions.…”

mentioning

confidence: 99%

Angiotensin II type _1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload

Herzig

Jobe

Aoki

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

185

125

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Hypertrophy of mammalian cardiac muscle is mediated, in part, by angiotensin II through an angiotensin II type 1a receptor (AT 1a R)-dependent mechanism. To understand how the level of AT 1a Rs is altered in this pathological state, we studied the expression of an injected AT 1a R promoter-luciferase reporter gene in adult rat hearts subjected to an acute pressure overload by aortic coarctation. This model was validated by demonstrating that coarctation increased expression of the ␣-skeletal actin promoter 1.7-fold whereas the ␣-myosin heavy chain promoter was unaffected. Pressure overload increased expression from the AT 1a R promoter by 1.6-fold compared with controls. Mutations introduced into consensus binding sites for AP-1 or GATA transcription factors abolished the pressure overload response but had no effect on AT 1a R promoter activity in control animals. In extracts from coarcted hearts, but not from control hearts, a Fos-JunB-JunD complex and GATA-4 were detected in association with the AP-1 and GATA sites, respectively. These results establish that the AT 1a R promoter is active in cardiac muscle and its expression is induced by pressure overload, and suggest that this response is mediated, in part, by a functional interaction between AP-1 and GATA-4 transcription factors.Pathological conditions resulting in increased cardiac workload generally are associated with activation of systemic and local renin-angiotensin systems and increased levels of circulating angiotensin II (AngII) (1, 2). However, little is understood about how AngII type 1a receptors (AT 1a R) are modulated under these same pathological conditions. AngII is a potent growth factor that mediates the hypertrophic growth of cardiac muscle cells and is a chemical mediator of stretchinduced cardiomyocyte hypertrophy (3-7). The interaction of AngII with AT 1a R activates a signal transduction cascade that effects the phosphorylation of serum response factor and p62 TCF by pp90 RSK and mitogen-activated protein kinase, respectively, resulting in increased c-fos gene expression (5-7). Hypertrophic stimuli also increase the level of AT1 a R mRNA in cardiomyocytes. A 3-fold increase in AT 1a R mRNA and a 2-fold increase in AT 1a R densities have been reported in spontaneously hypertensive and two kidney one-clip renovascular hypertensive rats with established cardiac hypertrophy (8). It is not known whether this increase in AT 1a R mRNA is mediated by a transcriptional or posttranscriptional mechanism.In this study, we use direct injection of DNA into the heart in conjunction with aortic coarctation (CoA) to study the activity of the AT 1a R promoter in the normal and pressureoverloaded rat heart. The AT 1a R promoter was found to be active in normal adult cardiac muscle, whereas gene expression was increased in response to an acute pressure overload (PO). The induced expression was blocked by mutation of either an AP-1 or a GATA binding site, however, these mutations had no effect on basal expression. Administration of the angiotensin-...

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mentioning

confidence: 99%

Angiotensin II type _1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload

Herzig

Jobe

Aoki

et al. 1997

Proc. Natl. Acad. Sci. U.S.A.

185

125

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“…It is noteworthy that rats treated with both antagonists showed a blunted carotid pressure elevation throughout the period of coarctation, resembling the change in pressure observed in nephrectomized rats, which was attributed almost exclusively to the mechanical factor of the constriction (16). For a more direct evaluation of the contributions of these humoral mechanisms we determined the changes of plasma renin activity (PRA), plasma AVP and plasma catecholamines (epinephrine and norepinephrine) after 15 and 45 min of aortic constriction (26). Plasma AVP concentration did not differ from that observed in control rats after 15 min of coarctation, but showed a five-fold increase after 45 min.…”

Section: The Renin-angiotensin System and Vasopressinmentioning

confidence: 99%

“…In conclusion, the different approaches used in our laboratory to investigate the physiopathogenesis of acute (45 min) aortic coarctation hypertension, i.e., pharmacological blockade of AVP and ANG II (25), renal denervation (47), electrolytic lesions of the median eminence of the hypothalamus (39), and plasma hormone (AVP, PRA and catecholamines) assays (26), support the hypothesis that some territory below the coarctation is able to trigger the release of AVP into the circulation under special conditions such as low renal perfusion pressure, leading AVP to play a role in the hypertensive response during aortic constriction.…”

Section: The Renin-angiotensin System and Vasopressinmentioning

confidence: 99%

Vasopressor mechanisms in acute aortic coarctation hypertension

Hc¹,

R²,

Mc³

1997

Braz J Med Biol Res

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Angiotensin II (ANG II) and vasopressin (AVP) act together with the mechanical effect of aortic constriction in the onset of acute aortic coarctation hypertension. Blockade of ANG II and AVP V 1 receptors demonstrated that ANG II acts on the prompt (5 min) rise in pressure whereas AVP is responsible for the maintenance (30-45 min) of the arterial pressure elevation during aortic coarctation. Hormone assays carried out on blood collected from conscious rats submitted to aortic constriction supported a role for ANG II in the early stage and a combined role for both ANG II and AVP in the maintenance of proximal hypertension. As expected, a role for catecholamines was ruled out in this model of hypertension, presumably due to the inhibitory effect of the sinoaortic baroreceptors. The lack of afferent feedback from the kidneys for AVP release from the central nervous system in rats with previous renal denervation allowed ANG II to play the major role in the onset of the hypertensive response. Median eminence-lesioned rats exhibited a prompt increase in proximal pressure followed by a progressive decline to lower hypertensive levels, revealing a significant role for the integrity of the neuroaxis in the maintenance of the aortic coarctation hypertension through the release of AVP. In conclusion, the important issue raised by this model of hypertension is the likelihood of a link between some vascular territory -probably renal -below the coarctation triggering the release of AVP, with this vasoconstrictor hormone participating with Ang II and the mechanical effect of aortic constriction in the acute aortic coarctation hypertension. Key words Mechanical vs renal factorFor a long time two schools of thought have attributed different mechanisms to chronic aortic coarctation hypertension. Whereas one school suggested that the mechanical effect of aortic constriction was the main factor promoting high blood pressure (1-3), others (4-6) argued that a renal factor was involved in the arterial pressure elevation. However, it was only in 1968 (7) that studies on young dogs with hypertension induced by chronic aortic coarctation hypertension provided a clear-cut demonstration that both factors, i.e., mechanical and renal factors, were operative in this model for hypertension. Later, these observations were confirmed in adult dogs submitted to aortic constriction, indicating a major role for the renal mechanisms in the development of hypertension, associated with a role played by aortic constriction (8).

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“…The physiopathogenesis of acute aortic coarctation hypertension has been well documented [5,6,[25][26][27]31]. Clamping the aorta between the renal arteries initially results in arterial and cardiac hypertrophy in response to the development of high blood pressure [5,6].…”

Section: Introductionmentioning

confidence: 99%

“…Clamping the aorta between the renal arteries initially results in arterial and cardiac hypertrophy in response to the development of high blood pressure [5,6]. Involvement of angiotensin II (Ang II) in this hypertensive process has been demonstrated by blockade of Ang II receptors or measurement of plasma renin activity, which was significantly increased following aortic constriction [5,6,[25][26][27]31]. On the other hand, the response of critical cardiovascular target organs to the increased renin-angiotensin system (RAS) in this model of hypertension has not been characterized.…”

Section: Introductionmentioning

confidence: 99%

Increased hypothalamic angiotensin-(1–7) levels in rats with aortic coarctation-induced hypertension

et al. 2007

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Since angiotensin (Ang) (1-7) injected into the brain blocked Ang II pressor actions in rats made hypertensive by aortic coarctation (CH), we examined systemic and tissue angiotensin peptide levels, specifically concentrating on the hypothalamic Ang-(1-7) levels. Plasma, heart and kidney isolated from CH rats showed increased levels of Ang I, Ang II and Ang-(1-7) compared with the normotensive group, with Ang II being the predominant peptide in heart and kidney. In the hypothalamus, equimolar amounts of Ang II and Ang-(1-7) were found in the sham group, whereas only Ang-(1-7) levels increased in CH rats. We conclude that aortic coarctation activates systemic and tissue renin-angiotensin system. The increased central levels of Ang-(1-7) in the CH rats suggest a potential mitigating role of this peptide in central control of the hypertensive process.

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Physiopathogenesis of acute aortic coarctation hypertension in conscious rats.

Cited by 26 publications

References 19 publications

Angiotensin II type _1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload

Angiotensin II type _1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload

Vasopressor mechanisms in acute aortic coarctation hypertension

Increased hypothalamic angiotensin-(1–7) levels in rats with aortic coarctation-induced hypertension

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Physiopathogenesis of acute aortic coarctation hypertension in conscious rats.

Cited by 26 publications

References 19 publications

Angiotensin II type 1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload

Angiotensin II type 1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload

Vasopressor mechanisms in acute aortic coarctation hypertension

Increased hypothalamic angiotensin-(1–7) levels in rats with aortic coarctation-induced hypertension

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Angiotensin II type _1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload

Angiotensin II type _1a receptor gene expression in the heart: AP-1 and GATA-4 participate in the response to pressure overload