Direct coronary vasodilator action of adrenomedullin is mediated by nitric oxide

Matteo, Robert De; May, Clive

doi:10.1038/sj.bjp.0705572

Cited by 29 publications

(15 citation statements)

References 34 publications

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“…AM's effect on cardiac output likely results from alterations in cardiac preload and afterload, baroreflex-induced augmentation of efferent cardiac sympathetic activity, and/or a direct positive inotropic action (18,19). However, others have demonstrated no evidence for AM acting as a positive inotroph (20,21). Indeed, AM-2 has recently been reported to decrease cardiac function (reduced dP/dt) in vivo in rats and in isolated perfused rat hearts (22).…”

Section: Discussionmentioning

confidence: 95%

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-2 in Normal Conscious Sheep

Charles¹,

Rademaker²,

Richards³

2006

Endocrinology

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Although blood pressure and heart rate effects have been reported for adrenomedullin 2 (AM-2), a new member of the calcitonin gene-related peptide superfamily, little information is available regarding other biological actions of systemically administered AM-2. Accordingly, we report for the first time the integrated hemodynamic, hormonal, and renal actions of the AM-2 in normal conscious sheep. AM-2 induced significant reductions in mean arterial pressure (P < 0.001). This was associated with dose-dependent rises in heart rate (P < 0.001) and cardiac output (P < 0.001) and dose-dependent falls in calculated total peripheral resistance (P < 0.001). Right atrial pressure was increased post infusion (P = 0.026), whereas hematocrit fell post infusion (P = 0.001). AM-2 also induced significant hormonal changes, particularly in the renin-angiotensin-aldosterone system where plasma renin activity was significantly activated (P < 0.001) associated with a dose-dependent rise in plasma aldosterone (P < 0.001). Plasma cAMP also rose in response to AM-2 (P < 0.001), as did circulating levels of the natriuretic peptides, particularly post infusion. In conclusion, iv infusions of AM-2 administered to normal conscious sheep induced significant hemodynamic actions including reduced mean arterial pressure and calculated total peripheral resistance and increased heart rate and cardiac output. Concurrently, AM-2 activated plasma cAMP, plasma renin activity, aldosterone, and the natriuretic peptides. With the exception of actions on aldosterone, these actions are similar to those previously reported for AM. Thus, AM-2 may be another important regulator of volume and pressure homeostasis and may play a role in the pathophysiology of heart disease.

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Section: Discussionmentioning

confidence: 95%

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-2 in Normal Conscious Sheep

Charles¹,

Rademaker²,

Richards³

2006

Endocrinology

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show abstract

“…The effect of AM on cardiac output likely results from alterations in cardiac preload and afterload, baroreflexinduced augmentation of efferent cardiac sympathetic activity, and/or a direct positive inotropic action. 19,20 However, others 21,22 have demonstrated no evidence for AM acting as a positive inotroph. Furthermore, AM-2 has been reported to decrease cardiac function (reduced dP/dt) in vivo in rats and in isolated perfused rat hearts.…”

Section: Discussionmentioning

confidence: 97%

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-5 in Normal Conscious Sheep

Charles

Rademaker

Richards

2011

Journal of Cardiovascular Pharmacology

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Although blood pressure effects have been reported for adrenomedullin 5 (AM-5), a newly identified member of the calcitonin gene-related peptide superfamily, little is known about other biological actions. We report the integrated hemodynamic, hormonal, and renal actions of AM-5 (10 and 100 ng·kg·min each for 90 minutes) in normal conscious sheep. AM-5 reduced the mean arterial pressure by 12 mm Hg at the end of the high dose (P < 0.001) in association with dose-dependent increments in the heart rate (40 beats/min--high dose, P < 0.001) and cardiac output (50%-high dose, P < 0.001) and dose-dependent falls in calculated total peripheral resistance (P < 0.001). Plasma renin activity (4-fold increment, P < 0.001), aldosterone (2-fold increment, P = 0.014), and cyclic adenosine monophosphate (50% increment, P < 0.001) all rose in response to high dose AM-5. Urine volume and sodium excretion were unchanged. In conclusion, it is observed that intravenous infusions of AM-5 administered to normal conscious sheep induced significant hemodynamic actions including reduced mean arterial pressure and calculated total peripheral resistance and increased heart rate and cardiac output. Concurrently, AM-5 activated plasma cyclic adenosine monophosphate, plasma renin activity, and aldosterone. These actions are similar to those previously reported for AM and AM-2. Thus, AM-5 may be an another important regulator of volume and pressure homeostasis and may play a role in the pathophysiology of heart disease.

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“…TGF-b 1 promotes extracellular matrix deposition and is involved in the development of LVH, arterial stiffness and renal fibrosis in hypertensive patients [58]. Adrenomedullin, a potent vasodilator [59] that also stimulates angiogenesis [60], is elevated in hypertensive patients compared with controls and declines after anti-hypertensive therapy [61].…”

Section: Angiogenic Growth Factor Levels In Hypertensionmentioning

confidence: 99%

Angiogenic growth factors and hypertension

2004

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Emerging evidence supports a novel view of hypertension as a disease of inadequate or aberrant responses to angiogenic growth factors (AGF). Patients with hypertension have reduced microvascular density, with some evidence supporting a primary role for rarefaction in causing hypertension. Two clinical models have demonstrated a link between inhibition of AGF activity and hypertension. A major side effect of bevacizumab, a monoclonal antibody to vascular endothelial growth factor (VEGF), is hypertension. Pre-eclampsia is accompanied by high circulating levels of soluble VEGF receptor-1, which forms inactive complexes with VEGF and placental growth factor (PlGF). Paradoxically, early studies have demonstrated high circulating levels of AGF in hypertension. Several mechanisms may account for this finding including increased vascular stretch, tissue ischemia, compensatory responses, decreased clearance or a combination of these mechanisms. High AGF in hypertension could contribute to clinical sequelae such as peripheral and pulmonary edema, microalbuminuria, and progression of atherosclerosis. However, a role for altered angiogenesis in the pathogenesis of hypertension or its sequelae has not been established. Novel studies to understand the roles of AGF in hypertensive patients are warranted.

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Direct coronary vasodilator action of adrenomedullin is mediated by nitric oxide

Cited by 29 publications

References 34 publications

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-2 in Normal Conscious Sheep

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-2 in Normal Conscious Sheep

Hemodynamic, Hormonal, and Renal Actions of Adrenomedullin-5 in Normal Conscious Sheep

Angiogenic growth factors and hypertension

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