Rapid Increase in Cardiac Adrenomedullin Gene Expression Caused by Acute Pressure Overload. Effect of the Renin-Angiotensin System on Gene Expression.

Hirano, Shuji; Imamura, Takuroh; Onitsuka, Hisamitsu; Matsuo, Tomohiro; Kïtamura, Kazuo; Koiwaya, Yasushi; Eto, Tanenao

doi:10.1253/circj.66.397

Cited by 10 publications

(7 citation statements)

References 41 publications

(40 reference statements)

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“…In line with our hypothesis, this study suggests the counter-regulatory action of BAY 41-2272 on the fibrotic process by inhibiting TGF-b1 gene expression, concomitant with attenuating myofibroblast transformation in the pressure-overloaded heart. The model of pressure overload induced by constricting the suprarenal abdominal aorta has been reported to exhibit the substantial RAS activation in the heart, while the circulating RAS was less affected, 21,22,32,33 suggesting that Ang II generation in the LV is likely to be associated with the progression of fibrosis. It is noted that BAY 41-2272 administration to AC rats has been shown to lower ACE gene expression and its activity, a main enzyme for Ang II generation in rats.…”

Section: Discussionmentioning

confidence: 99%

“…Pressure overload was induced by abdominal AC at the suprarenal level, as described earlier. 22 In brief, a 22-gauge needle was placed adjacent to the abdominal aorta proximal to the renal artery, and ligated tightly around the aorta and the adjacent needle. The needle was then removed, leaving the vessel constricted to the diameter of the needle.…”

Section: Animal Experimentsmentioning

confidence: 99%

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Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart

et al. 2009

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Cardiac fibrosis is a hallmark of cardiovascular remodeling associated with hypertension. The purpose of this study was to explore the effect and mechanism of soluble guanylate cyclase (sGC) stimulator BAY 41-2272, leading to intracellular cyclic guanosine monophosphate (cGMP) elevation, on the remodeling process induced by pressure overload. Seven-week-old male Wistar rats with hypertension induced by suprarenal aortic constriction (AC) were treated orally with 2 mg kg À1 day À1 of BAY 41-2272 for 14 days. BAY 41-2272 had no effects on blood pressure, but decreased AC-induced collagen accumulation in the left ventricle (LV), inhibiting the number of myofibroblasts and gene expressions of transforming growth factor-b1 and type 1 collagen. In addition, the antifibrotic action of BAY 41-2272 was accompanied by reducing AC-induced angiotensin-converting enzyme (ACE) mRNA and its enzymatic activity, and angiotensin II concentration in LV. In cultured cardiac fibroblasts, BAY 41-2272 inhibited ACE synthesis and myofibroblast transformation, accompanied by elevating the intracellular cGMP concentration. These results suggest that sGC stimulator BAY 41-2272 might be effective to reduce fibrosis in hypertensive heart disease by attenuating angiotensin II generation through myofibroblast transformation.

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Section: Discussionmentioning

confidence: 99%

Section: Animal Experimentsmentioning

confidence: 99%

Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart

et al. 2009

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“…Two animal models of acute heart stress, namely, AMI (10) and PO (5,12,18), were used to estimate the relationship between the level of Reg expression and the intensity of the Fig. 2, B and C. Note the difference of vertical scales between A and B.…”

Section: Discussionmentioning

confidence: 99%

Activation of regenerating geneRegin rat and human hearts in response to acute stress

Kiji¹,

Dohi²,

Takasawa³

et al. 2005

American Journal of Physiology-Heart and Circulatory Physiology

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Recently, the regenerating gene ( Reg) has been documented to play an important role in various regenerating tissues, but it is unknown whether the Reg gene could be activated in the heart. The aim of this study was to reveal the transcriptional activation of Reg in the heart in response to heart stress. We first found REG-1 protein expression in human hearts obtained from autopsied patients who died of myocardial infarction. REG protein was immunohistochemically stained in a fine granular pattern in the cytoplasm of cardiomyocytes. To demonstrate the activation profiles of Reg gene expression in the heart, we quantified the levels of Reg-1 mRNA in rat hearts after coronary artery ligation using real-time RT-PCR. Transient Reg-1 mRNA activation, peaking at 12 h after coronary ligation, was observed mainly in the atria, which was sevenfold higher compared with hearts with pressure overload due to aortic constriction. In contrast, Reg receptor mRNA was expressed intensely in damaged ventricles. Furthermore, Western blot analysis showed the corresponding pattern of Reg protein secretion into the serum after loading, and circulating levels of the protein after myocardial infarction were higher than those after aortic constriction. In conclusion, our results demonstrate for the first time the presence of the Reg/Reg receptor system in damaged hearts. In view of emerging evidence of Reg for tissue regeneration in a variety of tissues/organs, it is proposed that the damaged heart may be a target for Reg action and that Reg may protect against acute heart stress.

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“…The production of AM in myocytes is augmented not only by me− chanical stretching, but also by Ang II stimulation and partially through AT1 receptors, which suggests local interaction between AM and Ang II in stretched myocytes [8]. Likewise, in vivo studies have indicated that ventricular AM production might be partly affected by Ang II in the pressure−overloaded rat model produced by aortic banding [17]. This is because although candesartan, quinapril (an angiotensin−converting inhibitor), and manidipine (a calcium channel blocker) decrease blood pressure to compar− able levels, candesartan and quinapril completely suppress ventricular AM expression, whereas manidipine does not.…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Stimulates Cardiac Adrenomedullin Production and Causes Accumulation of Mature Adrenomedullin Independently of Hemodynamic Stressin Vivo

Onitsuka

Imamura²,

Yamaga³

et al. 2005

Horm Metab Res

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Adrenomedullin is a potent hypotensive peptide that may act on myocytes to inhibit hypertrophy and on fibroblasts to inhibit growth in vitro induced by mechanical stretching and angiotensin II. Adrenomedullin is processed from the inactive intermediate adrenomedullin precursor with a glycine extension, which is subsequently converted to biologically active mature adrenomedullin by enzymatic amidation. Total adrenomedullin is the sum of intermediate and mature adrenomedullin. We examined the effect of a subpressor dose of angiotensin II on the production of left ventricular adrenomedullin and on protein levels of mature adrenomedullin in the left ventricle in vivo. We also investigated whether the effect is mediated by the angiotensin II type 1 receptor. Concentrations of total and mature adrenomedullin in the left ventricle and mature adrenomedullin-to-intermediate adrenomedullin ratio were significantly increased by angiotensin II infusion, regardless of pressure overload. Total and mature adrenomedullin concentrations significantly correlated with the weight of the left ventricle. Furthermore, increased adrenomedullin gene expression and protein levels were completely suppressed by a subdepressor dose of angiotensin II type 1 receptor blocker. In conclusion, angiotensin II stimulates the production of cardiac adrenomedullin and accumulates mature adrenomedullin in the left ventricle independently of hemodynamic stress. These processes are partially regulated through the angiotensin II type 1 receptor in vivo.

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Rapid Increase in Cardiac Adrenomedullin Gene Expression Caused by Acute Pressure Overload. Effect of the Renin-Angiotensin System on Gene Expression.

Cited by 10 publications

References 41 publications

Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart

Pressure-independent effects of pharmacological stimulation of soluble guanylate cyclase on fibrosis in pressure-overloaded rat heart

Activation of regenerating geneRegin rat and human hearts in response to acute stress

Angiotensin II Stimulates Cardiac Adrenomedullin Production and Causes Accumulation of Mature Adrenomedullin Independently of Hemodynamic Stressin Vivo

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