Tissue-Specific Regulation of Angiotensinogen Gene Expression in Spontaneously Hypertensive Rats

Tamura, Kouichi; Umemura, Satoshi; Nyui, Nobuo; Yamakawa, Tadashi; Yamaguchi, Satoshi; Ishigami, Tomoaki; Tanaka, Shun‐ichi; Tanimoto, Koichi; Takagi, Nobuyoshi; Sekihara, Hisahiko; Murakami, Kazuo; Ishii, Masao

doi:10.1161/01.hyp.27.6.1216

Cited by 61 publications

(37 citation statements)

References 55 publications

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“…Our previous studies showed that the progression of hypertension did not affect liver angiotensinogen expression in genetically hypertensive rats. 8,14 As expected, the liver ATRAP to AT1R expression ratio was not affected during the development of hypertension or by treatment with olmesartan in the present study. Several previous studies demonstrated that activation of the kidney angiotensinogen expression and AT1R pathway plays an important role in the pathogenesis of hypertension and renal injury from an early phase.…”

Section: Discussionsupporting

confidence: 84%

“…The rats were housed and systolic blood pressure was measured by the tail cuff method (BP-monitor MK-2000; Muromachi Kikai Co) at 6 and 14 weeks of age as described previously. 8 The BP-monitor MK-2000 made it possible to measure blood pressure without preheating animals to avoid very stressful condition. The rats were anesthetized and the tissues were placed into liquid nitrogen at the end of the experimental periods.…”

Section: Expression Of Atrap and At1r In Wistar-kyoto Rats And Shrmentioning

confidence: 99%

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Effect of Olmesartan on Tissue Expression Balance Between Angiotensin II Receptor and Its Inhibitory Binding Molecule

et al. 2008

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Abstract-We previously cloned a novel molecule interacting with angiotensin II (Ang II) type 1 receptor protein (ATRAP) and showed it to be an endogenous inhibitor of Ang II type 1 receptor signaling in cardiovascular cells.In this study, we tested a hypothesis that the balance of tissue expression of ATRAP and Ang II type 1 receptor is regulated in a tissue-specific manner during the development of hypertension and related cardiac hypertrophy. T he renin-angiotensin system has been implicated in the pathogenesis of hypertension and cardiovascular remodeling based on the generation of angiotensin II (Ang II), a key regulator of cardiovascular homeostasis. The pathophysiological actions of Ang II are mediated by the Ang II type 1 receptor (AT1R). AT1R activates G proteins through the third intracellular loop and the intracellular carboxyl-terminal tail of the receptor. 1 The carboxyl-terminal end of AT1R is involved in the control of AT1R internalization independently of G protein coupling and plays an important role in linking receptor-mediated signal transduction to the specific biological response to Ang II such as cardiovascular remodeling. 2 We previously cloned a novel AT1R-associated protein (ATRAP) that specifically interacts with the carboxylterminal domain of AT1R. 3,4 We showed that ATRAP is expressed in many tissues such as the kidney, heart, and liver. 5 Previous studies showed that ATRAP exerts its inhibitory action on AT1R signaling by promoting a constitutive internalization of AT1R and decreasing the cell surface AT1R number. 6,7 In this study, we examined whether the expression of ATRAP is regulated in a tissue-specific manner in spontaneously hypertensive rats (SHR). We further investigated whether the balance of tissue expression of ATRAP and AT1R in SHR is modulated during the development of hypertension and by the treatment with the AT1R-specific blocker olmesartan at either a depressor or subdepressor dose.

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Section: Discussionsupporting

confidence: 84%

Section: Expression Of Atrap and At1r In Wistar-kyoto Rats And Shrmentioning

confidence: 99%

Effect of Olmesartan on Tissue Expression Balance Between Angiotensin II Receptor and Its Inhibitory Binding Molecule

et al. 2008

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“…For example, acute or chronic ICV administration of AII receptor antagonists markedly reduced BP in the adult spontaneously hypertensive rat (SHR), 12,20 and chronic ICV-converting enzyme inhibitor prevented the development of hypertension in young SHRs. 21 Indeed, compared with normotensive WistarKyoto rats, SHRs have elevated levels of brain RAS components 51,52 but normal plasma AII levels. Moreover, direct microinjection of losartan into the anterior hypothalamic area, an intrinsic brain site rich in AT-1 receptors with projections to PVN and SON, caused depressor responses in SHR but not WKY, 37 suggesting a role for endogenous AII at this intrinsic brain site in SHR.…”

Section: Discussionmentioning

confidence: 99%

The Brain Renin-Angiotensin System Contributes to the Hypertension in Mice Containing Both the Human Renin and Human Angiotensinogen Transgenes

Davisson

Yang

Beltz

et al. 1998

Circulation Research

136

155

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Abstract-We have previously shown that mice transgenic for both the human renin and human angiotensinogen genes (RAϩ) exhibit appropriate tissue-and cell-specific expression of both transgenes, have 4-fold higher plasma angiotensin II (AII) levels, and are chronically hypertensive. However, the relative contribution of circulating and tissue-derived AII in causing hypertension in these animals is not known. We hypothesized that the brain renin-angiotensin system contributes to the elevated blood pressure in this model. To address this hypothesis, mean arterial pressure (MAP) and heart rate were measured in conscious, unrestrained mice after they were instrumented with intracerebroventricular cannulae and carotid arterial and jugular vein catheters. Intracerebroventricular administration of the selective AII type 1 (AT-1) receptor antagonist losartan (10 g, 1 L) caused a significantly greater peak fall in MAP in RAϩ mice than in nontransgenic RAϪ controls (Ϫ29Ϯ4 versus Ϫ4Ϯ2 mm Hg, PϽ0.01). To explore the mechanism of a central renin-angiotensin system-dependent hypertension in RAϩ mice, we determined the relative depressor responses to intravenous administration of the ganglionic blocking agent hexamethonium (5 mg/kg) or an arginine vasopressin (AVP) V 1 receptor antagonist (AVPX, 10 g/kg). Hexamethonium caused equal lowering of MAP in RAϩ mice and controls (Ϫ46Ϯ3 versus Ϫ52Ϯ3, PϾ0.05), whereas AVPX caused a significantly greater fall in MAP in RAϩ compared with RAϪ mice (Ϫ24Ϯ2 versus Ϫ6Ϯ1, PϽ0.01). Consistent with this was the observation that circulating AVP was 3-fold higher in RAϩ mice than in control mice. These results suggest that increased activation of central AT-1 receptors, perhaps those located at sites involved in AVP release from the posterior pituitary gland, plays a role in the hypertension in RAϩ mice. Furthermore, our finding that both human transgenes are expressed in brain regions of RAϩ mice known to be involved in cardiovascular regulation raises the possibility that augmented local production of AII and increased activation of AT-1 receptors at these sites is involved. (Circ Res. 1998;83:1047-1058.)Key Words: transgenic mice Ⅲ angiotensin Ⅲ blood pressure Ⅲ genetics Ⅲ pharmacology I t is well established that blood-borne angiotensin II (AII), the effector peptide of the renin-angiotensin system (RAS), plays a major role in the regulation of arterial blood pressure (BP) and volume homeostasis through its interaction with specific AII receptors present in vascular smooth muscle, kidney, and adrenal gland. Stimulation of these peripheral AII receptors leads to elevations in BP through increased vascular resistance, cardiac output, sodium reabsorption, and blood volume.1 However, in addition to these well-known actions at peripheral sites, AII also contributes to BP and volume regulation through its receptor-mediated effects on neurons located within the central nervous system (CNS). Indeed, central administration of AII causes increases in BP, antidiuresis, drinking, and salt appetite.2 This, ...

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“…Furthermore, the functional significance of tissue angiotensinogen has been elucidated in SHR. The expression of tissue AGTis regulated differently in SHRand its corresponding normotensive control, the Wistar Kyoto (WKY)rat, and the development of hypertension is associated at least temporarily with increases in cardiac and adipogenic AGTmRNAin SHR (6). The transfection of antisense oligonucleotides against rat AGTresults in a transient decrease in the high blood pressure of SHRaccompanied by a decrease both in hepatic AGTmRNAand in plasma angiotensin II levels (7).…”

Section: Angiotensinogenmentioning

confidence: 99%

Recent Aspects in the Genetic Renal Mechanisms Involved in Hypertension.

1999

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The kidney plays an important role in the blood pressure regulation primarily by modulating tubular sodium reabsorption. Various hormones, vasoactive peptides, autacoids and transporters or channels in renal tubules are involved in this process. Genes associated with renal tubular sodium handling are possibly related to the development of hypertension. Genes of the renin-angiotensin-aldosterone system are thought to be especially important as causal genes of hypertension. Na-K-ATPase, biochemically equal to Na pump, exists on the basolateral membrane of renal epithelial cells. It plays a central role in Na reabsorption and creates a driving force for transepithelial transport. Na-K-ATPaseactivity is regulated by adducin, a membrane-bound skeletal protein, as well as by several hormones such as dopamine, endogenous ouabain-like factor or cytochrome P450 metabolites. Genes of these factors involved in Na-K-ATPaseregulation should be related to the development of hypertension. The endothelin system, atrial natriuretic peptide and nitric oxide regulate the tonus of blood vessels as well as renal sodiumexcretion. Several reports have indicated that genes of these substances are crucial in the pathogenesis of hype rtension. (Internal Medicine 38: 919-926, 1999)

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Tissue-Specific Regulation of Angiotensinogen Gene Expression in Spontaneously Hypertensive Rats

Cited by 61 publications

References 55 publications

Effect of Olmesartan on Tissue Expression Balance Between Angiotensin II Receptor and Its Inhibitory Binding Molecule

Effect of Olmesartan on Tissue Expression Balance Between Angiotensin II Receptor and Its Inhibitory Binding Molecule

The Brain Renin-Angiotensin System Contributes to the Hypertension in Mice Containing Both the Human Renin and Human Angiotensinogen Transgenes

Recent Aspects in the Genetic Renal Mechanisms Involved in Hypertension.

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