Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension

Shimokubo, Toru; Sakata, Junichiro; Kïtamura, Kazuo; Kangawa, Kenji; Matsuo, Hisayuki; Eto, Tanenao

doi:10.1016/0024-3205(95)02155-c

Cited by 69 publications

(30 citation statements)

References 14 publications

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“…Our results are inconsistent with those of previous studies of other hypertensive rat models, such as renovascular hypertensive rats (10), Dahl-salt sensitive rats (11), and pulmonary hypertensive rats (12). The assay system that we used to measure rat AM was the same as that used in earlier studies, and the plasma AM levels in WKY/ Izm were similar to those reported in other normotensive rats (4).…”

Section: Discussioncontrasting

confidence: 99%

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Decrease in Circulating and Urine Adrenomedullin Concentrations in Stroke-Prone Spontaneously Hypertensive Rats.

et al. 1998

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Adrenomedullin(AM) is a peptide with potent vasodilatory and hypotensive properties. Plasma AM levels in rats with experimentally induced hypertension, such as Dahl salt-sensitive rats and two-kidney, one-clip hypertensive rats, are higher than those in normotensive rats. We previously noted, however, that plasma AM levels in spontaneously hypertensive rats (SHR) are similar to those in Wistar-Kyoto rats. To define the role of AM in rats with severe hypertension, we investigated changes in circulating and tissue AM levels in stroke-prone spontaneously hypertensive rats (SHRSP/Izm Adrenomedullin (AM) is a novel hypotensive peptide discovered in human pheochromocytoma tissue by monitoring activity with respect to increasing cyclic adenosine monophosphate (cAMP) in rat platelets (1). AM consists of 52 amino acids with an intramolecular disulfide bridge. It shares slight homology with calcitonin gene-related peptide (CGRP). Appreciable concentrations of AM are found in normal human plasma and urine (2, 3). Furthermore, abundant AM mRNA is expressed in the adrenal medulla, heart, lung, and kidney in both humans and rats (2, 4). The intravenous injection of AM elicits potent, long-lasting, vasodilating and hypotensive effects in anesthetized rats (5). Ishimitsu et al. have reported that plasma AM levels are higher in patients with essential hypertension than in normotensive subjects. Moreover, the plasma AM level positively correlates with the severity of hypertension (6). These findings suggest that AM may act as a circulating hormone in the regulation of blood pressure. Shimokubo et al. (7) reported that the plasma AM levels in spontaneously hypertensive rats (SHR) were not higher than those in Wistar-Kyoto rats (WKY). However, there is no report on the circulating and tissue AM levels in stroke-prone spontaneously hypertensive rats (SHRSP/Izm), and the pathophysiological role of AM in severe hypertension is still obscure. As the first step in elucidating the pathophysiological role of AM in severe hypertension, we measured plasma, urine, and tissue AM levels and AM gene expression in 15-wk-old SHRSP/Izm, and compared the results with those in age-matched Wistar-Kyoto rats (WKY/Izm). Methods AnimalsWe used 15-wk-old male SHRSP/Izm (n = 8) and age-matched male WKY/Izm (n = 8) for measurement of immunoreactive rat AM (ir-rAM) and for RNA blot analysis. All rats were obtained from the

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Section: Discussioncontrasting

confidence: 99%

“…Several studies report that ventricular hypertrophy is closely related to the elevated ventricular AM gene expression in SHR (7), Dahl-salt sensitive rats (I1), and pulmonary hypertensive rats (12). Thus far, the reasons for these conflicting results remain unclear.…”

Section: Discussionmentioning

confidence: 99%

Decrease in Circulating and Urine Adrenomedullin Concentrations in Stroke-Prone Spontaneously Hypertensive Rats.

et al. 1998

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“…However, the association of myocyte remodeling with the transition from hypertrophy to failure in the right ventricle has rarely been investigated. [2][3][4][5][6] In this study, we prepared pulmonary hypertensive model rats by administering a pyrrolizine alkaloid plant extract, monochrotaline (MCT). Using this rat model, we investigated the relationship between right ventricular hypertrophy, right ventricular dysfunction, and myocyte remodeling.…”

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Myocyte Morphological Characteristics Differ Between the Phases of Pulmonary Hypertension-Induced Ventricular Hypertrophy and Failure

et al. 2006

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SUMMARYPulmonary hypertensive model rats were prepared by treating them with monochrotaline (MCT). Using these model rats, we examined myocyte remodeling in the right ventricle in response to increased right ventricular pressure.Male Sprague-Dawley rats were divided into 2 groups. Group M received MCT and group C received physiological saline. The 2 groups were examined at weeks 2, 5, and 7 after MCT or saline injection, respectively. At week 2, a significant difference in cell form was not observed in either group. At week 5, cell volume and myocyte cross-sectional area (CSA) of the right ventricle in group M were significantly greater than those in group C. At week 7, cell volume, CSA, and cell length of the right ventricle in group M were all significantly greater than those in group C. These results suggest that pulmonary hypertension causes hypertrophy, accompanying the enlargement of CSA in the right ventricle, and that cells lengthen in the phase of right ventricular failure.These results are similar to the changes observed in left ventricular myocytes due to overload pressure. Both right and left ventricular myocytes may share a common mechanism for myocyte remodeling as an adaptive and maladaptive response to increased ventricular pressure. (Int Heart J 2006; 47: 629-637)

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“…9 -11 Previous studies have also revealed that ventricular AM levels are increased in several hypertensive models with cardiac hypertrophy. [17][18][19] Left ventricular AM gene expression has been reported to increase in response to aortic banding in rats within 24 hours, 20 whereas Kaiser et al 21 did not find changes in AM mRNA levels during aortic banding from 30 minutes up to 28 days. We have recently reported that AM gene expression is increased in the left ventricle by pressure overload within 2 hours, 22 whereas in a recent study, ventricular AM gene expression was upregulated only in advanced heart failure.…”

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confidence: 81%

Endothelin-1–Independent and Angiotensin II–Independent Induction of Adrenomedullin Gene Expression

et al. 2001

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Abstract-Adrenomedullin (AM) may function as an autocrine and/or paracrine factor in the heart, but the exact mechanisms regulating cardiac AM gene expression are unknown. The aim of the present study was to characterize the precise time course of induction of atrial and ventricular AM gene expression during pressure overload and to study whether endothelin-1 or angiotensin II plays a causal role in the activation of cardiac AM gene expression. The pressure overload was produced by arginine-vasopressin (AVP, 0.05 g/kg per minute IV) infusion for 15 minutes, 30 minutes, 1 hour, 2 hours, or 4 hours in conscious rats. A significant increase in left ventricular AM mRNA levels was seen after 2 hours of pressure overload in the left ventricle and after 30 minutes in the left atrium. The left atrial immunoreactive AM (ir-AM) levels decreased significantly after 2 hours of pressure overload. Plasma ir-AM levels increased slightly in response to 4 hours of AVP infusion. Bolus injections of bosentan (mixed ET A /ET B receptor antagonist, 10 mg/kg IV), losartan (AT 1 receptor antagonist, 10 mg/kg IV), and their combination had no effect on the increase of cardiac AM mRNA and ir-AM levels produced by 2 hours of pressure overload. In addition, losartan, bosentan, and their combination did not affect plasma ir-AM levels in the vehicle-infused and AVP-infused animals. The present study indicates that cardiac AM gene expression is rapidly upregulated in response to pressure. The induction of ventricular and atrial AM gene expression by pressure overload is angiotensin II-independent and endothelin-1-independent.

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Augmented adrenomedullin concentrations in right ventricle and plasma of experimental pulmonary hypertension

Cited by 69 publications

References 14 publications

Decrease in Circulating and Urine Adrenomedullin Concentrations in Stroke-Prone Spontaneously Hypertensive Rats.

Decrease in Circulating and Urine Adrenomedullin Concentrations in Stroke-Prone Spontaneously Hypertensive Rats.

Myocyte Morphological Characteristics Differ Between the Phases of Pulmonary Hypertension-Induced Ventricular Hypertrophy and Failure

Endothelin-1–Independent and Angiotensin II–Independent Induction of Adrenomedullin Gene Expression

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