Adrenomedullin: Changes in Circulating and Cardiac Tissue Concentration in Dahl Salt-Sensitive Rats on a High-Salt Diet

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

doi:10.3109/10641969609097910

Cited by 50 publications

(24 citation statements)

References 25 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: 57%

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: 57%

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

et al. 1998

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“…These findings are consistent with previous observations in DS rats at the CHF stage. 27 In the present study, we extended our investigation to include the AM receptor system and 2 molecular forms of AM in the failing LV and found that the AM receptor components, CRLR, RAMP2, and RAMP3, were maintained at higher levels in the progression to HF. Recent studies showed that gene expression of RAMP2, CRLR, and AM in the ventricles of rats with old myocardial infarction were increased compared with those of shamoperated rats.…”

Section: Further Activation Of Am System During Transition To Chfmentioning

confidence: 94%

Ventricular Adrenomedullin System in the Transition From LVH to Heart Failure in Rats

et al. 2003

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Abstract-We investigated whether adrenomedullin (AM) participates in the pathophysiology during the transition from left ventricular hypertrophy (LVH) to heart failure (HF). We used the Dahl salt-sensitive (DS) rat model, in which systemic hypertension causes LVH at the age of 11 weeks, followed by HF at the age of 18 weeks. Two molecular forms of AM levels in the plasma and myocardium at the LVH stage were significantly elevated compared with those in controls, and they were further increased at the HF stage. Interestingly, the LV tissue AM-mature/AM-total ratio was higher only in the HF group than in controls and LVH. The LV tissue AM-mature/AM-total ratio, AM-mature, and AM-total concentrations had close relations with the LV weight/body weight (rϭ0. 72, rϭ0.79, and rϭ0.70, respectively; all PϽ0.001). AM gene expression was significantly increased at the LVH stage and was further increased at the HF stage. Furthermore, gene expression of AM receptor system components such as calcitonin receptor-like receptor (CRLR), receptor activity-modified protein 2 (RAMP2), and RAMP3 were significantly increased at the stage of LVH and HF. Regarding other neurohumoral factors, plasma renin and aldosterone levels were not increased at the LVH stage but were increased at the HF stage, whereas atrial natriuretic peptide was increased in both the plasma and myocardium at the LVH stage and was further increased at the HF stage. These results suggest that induction of the cardiac AM system, including the ligand, receptor, and amidating activity, may modulate pathophysiology during the transition from LVH to HF in this model. Key Words: adrenomedullin Ⅲ hypertension, sodium dependent Ⅲ hypertrophy, left ventricular Ⅲ heart failure Ⅲ rats, Dahl M any neurohumoral factors are involved in the pathophysiology of heart failure (HF). 1 Therefore, it is very important to investigate the pathophysiological roles of newly identified neurohumoral factors in HF because these studies may lead to the development of a new drug. 1 In fact, angiotensin-converting enzyme inhibitors, ␤-blockers, and angiotensin receptor blockers, which were produced in this field of research, are now used in many patients with HF and contribute to the improvement in prognosis and quality of life in this syndrome. Recent studies indicate that most patients with HF have a history of hypertension and/or left ventricular hypertrophy (LVH). 2,3 Furthermore, it has been suggested that treating high blood pressure actually prevents HF. 4 These results suggest that hypertension and LVH are the most common risk factors for HF, and they contribute a large proportion of the HF cases. 5 Therefore, it seems important to assess the derangement of neurohumoral factors during the transition from LVH to HF.Adrenomedullin (AM) is a 52-amino acid novel vasodilatory peptide that was originally discovered in human pheochromocytoma tissue. 6 AM is widely distributed in various tissues and organs, including the heart. 7 The plasma levels of AM are elevated in various pathophysiologica...

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“…In addition, recent studies have shown that the plasma concentration of AM was increased in patients with congestive heart failure (16,17), and that AM immunoreactivity was markedly increased in the failing heart ventricle (18). AM expression was also shown to be increased in rat hypertrophic ventricles (19,20). These findings suggest that AM levels in the heart may be correlated to the degrees of congestive heart failure or cardiac hypertrophy.…”

Section: Cardiovascular Tissuementioning

confidence: 86%

Immunohistological Localization and Possible Functions of Adrenomedullin

et al. 2003

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Adrenomedullin: Changes in Circulating and Cardiac Tissue Concentration in Dahl Salt-Sensitive Rats on a High-Salt Diet

Cited by 50 publications

References 25 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.

Ventricular Adrenomedullin System in the Transition From LVH to Heart Failure in Rats

Immunohistological Localization and Possible Functions of Adrenomedullin

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