Adrenomedullin: A Possible Autocrine or Paracrine Inhibitor of Hypertrophy of Cardiomyocytes

Tsuruda, Toshihiro; Kato, Jun; Kïtamura, Kazuo; Kuwasako, Kenji; Imamura, Takuroh; Koiwaya, Yasushi; Tsuji, Tetsuo; Kangawa, Kenji; Eto, Tanenao

doi:10.1161/01.hyp.31.1.505

Cited by 165 publications

(123 citation statements)

References 32 publications

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“…In addition, AM has been shown to be synthesized and secreted from cultured cardiac myocytes, mesangial cells, and vascular endothelial and smooth muscle cells (15)(16)(17)(18). It has been reported that both plasma ANP and BNP concentrations in hypertensive patients are higher than those in normotensive controls (19,20), and consistent results were obtained in the present study.…”

Section: Discussionsupporting

confidence: 91%

“…Indeed, PRA in the patients with MHT was much higher than the upper limit of the normal range and was reduced by antihypertensive treatment. The results of in vitro experiments suggest that angiotensin II is an important factor stimulating the production and secretion of AM in cardiac myocytes and vascular smooth muscle cells (15,18). In any case, further studies are necessary to identify the source and mechanism for the increased plasma AM levels in patients with MHT and EHT.…”

Section: Discussionmentioning

confidence: 99%

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Plasma Adrenomedullin and Natriuretic Peptides in Patients with Essential or Malignant Hypertension.

Kato¹,

Kïtamura²,

Matsui³

et al. 1999

Hypertens Res

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Adrenomedullin(AM), a potent vasodilator and natriuretic peptide, is found in human blood. To investigate the pathophysiological role of AM in essential and malignant hypertension (EHT and MHT), we measured the plasma concentrations of AM in patients with EHT of WHO stage I or II (n = 42) and in those with MHT (n = 9) by a specific radioimmunoassay, and compared these concentrations with those in normotensive controls (n = 46). The plasma concentrations of atrial and brain natriuretic peptides (ANP and BNP) in these subjects were also measured by immunoradiometric assays, and their relations to plasma AM were examined. The plasma AM level in the EHT patients (7.15 ± 0.21 pmol/l, mean ± SEM) was significantly (p < 0.01) higher than that in the normotensive controls (6.14 ± 0.25 pmol/1), and a further elevation was observed in the MHT patients (14.1 ± 3.8 pmol/l). Similar elevations of plasma ANP and BNP were seen in the two patient groups. The plasma AM level significantly (p < 0.01) correlated with not only the systolic (r = 0.44) and diastolic (r = 0.46) blood pressures, but also with the plasma levels of ANP (r= 0.43) and BNP (r= 0.43). The elevated plasma concentration of AM in the MHT patients decreased significantly (p < 0.05) after antihypertensive treatment, and the plasma ANP and BNP levels similarly declined. These results suggest that AM may participate, along with ANP and BNP, in mechanisms counteracting a further elevation of blood pressure in patients with EHT and MHT. (Hypertens Res 1999; 22: 61-65) Key Words: adrenomedullin, natriuretic peptides, essential hypertension, malignant hypertension Adrenomedullin (AM) is a potent vasodilator peptide that was first detected in a human pheochromocytoma while monitoring cyclic AMP (cAMP) in rat platelets (1). The development of a specific radioimmunoassay (RIA) revealed that AM is present not only in the normal human adrenal medulla but also in tissues such as aorta, kidney, lung, and cardiac atrium and ventricle, where AM mRNA is abundantly expressed (2, 3) . High concentrations of AM were also found to circulate in the blood of humans (4). When injected intravenously, synthetic AM exerts a potent hypotensive action, accompanied by a marked reduction of total peripheral resistance in rats (5). Ebara et al. observed increases in urinary volume and sodium excretion after an intrarenal arterial injection of AM in dogs (6). Atrial and brain natriuretic peptides (ANP and BNP) are cardiac hormones thought to act against elevation of blood pressure and retention of body fluid in cardiovascular diseases such as hypertension and heart failure through their vasodilator and natriuretic effects (7) . ANP and BNP exert their biological actions via an accumulation of intracellular cyclic GMP (cGMP) (7), whereas many of the actions of AM are mediated by cAMP (8). Since the AM actions are similar to those of ANP and BNP despite differences in their intracellular signaling systems, we hypothesized that AM functions along with ANP and BNP to act against further elevati...

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Section: Discussionsupporting

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Plasma Adrenomedullin and Natriuretic Peptides in Patients with Essential or Malignant Hypertension.

Kato¹,

Kïtamura²,

Matsui³

et al. 1999

Hypertens Res

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“…26 After culturing the cells under the serum-free Dulbecco's modified Eagle's medium containing 10 mg ml À1 insulin, 5 mg ml À1 transferrin and 7 ng ml À1 sodium selenite for 48 h, BAY 41-2272 (10 À6 and 10 À5 mol l À1 ) was then added to the medium to examine the intracellular cGMP elevation.…”

Section: Soluble Guanylate Cyclase and Cardiac Fibrosis H Masuyama Et Almentioning

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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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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“…In rat mesangial cells, adrenomedullin inhibits mitogenesis even under quiescence and suppresses MAPK activity (52,53). In cultured neonatal rat cardiocytes and cardiac fibroblasts, adrenomedullin suppresses cell growth (54,55). Certain cancer cells do not proliferate in response to adrenomedullin, and some of these cell lines show a growth-inhibitory response with elevation of intracellular cAMP (56).…”

mentioning

confidence: 99%

Regulation of Cell Growth and Apoptosis by Adrenomedullin

Shichiri

Hirata

2003

Hypertens Res

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Adrenomedullin: A Possible Autocrine or Paracrine Inhibitor of Hypertrophy of Cardiomyocytes

Cited by 165 publications

References 32 publications

Plasma Adrenomedullin and Natriuretic Peptides in Patients with Essential or Malignant Hypertension.

Plasma Adrenomedullin and Natriuretic Peptides in Patients with Essential or Malignant Hypertension.

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

Regulation of Cell Growth and Apoptosis by Adrenomedullin

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