Adrenomedullin 2 attenuates the pressor but not adrenal responses to angiotensin II in conscious sheep

Charles, Christopher J.; Rademaker, Miriam T.; Nicholls, M. Gary; Richards, A. Mark

doi:10.1016/j.peptides.2010.02.010

Cited by 4 publications

(4 citation statements)

References 37 publications

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“…31 In contrast, results from earlier studies show no evidence for the inhibition of endogenous aldosterone levels or angiotensin II-stimulated aldosterone secretion by AM-2 in normal conscious sheep. 8,32 The results from this study show that AM-5 induces parallel increases in PRA and plasma aldosterone. Thus, the actions of AM-5 on plasma aldosterone seem more similar to those of AM 18 than those previously reported for AM-2, 8 at least in normal conscious sheep.…”

Section: Discussionmentioning

confidence: 57%

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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Section: Discussionmentioning

confidence: 57%

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

Charles

Rademaker

Richards

2011

Journal of Cardiovascular Pharmacology

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“…Therefore, AM2/ IMD may not have a suppressive action on aldosterone secretion, unlike AM, or may rather stimulate the aldostertone secretion from adrenal cortex. In addition, AM2/ IMD had no suppressive effects on aldosterone response to angiotensin II in conscious sheep in contrast to AM (Charles et al 2010). In experimental heart failure sheep, however, plasma aldosterone levels were not significantly altered during the infusion of human AM2/IMD 1-47 despite the increase in renin activity, and therefore, the aldosterone/ plasma renin activity ratio was reduced (Rademaker et al 2008).…”

Section: Effects Of Adrenomedullin 2/intermedin On the Adrenal Hormonmentioning

confidence: 85%

Adrenomedullin 2/Intermedin in the Hypothalamo–Pituitary–Adrenal Axis

et al. 2010

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Adrenomedullin 2/intermedin (AM2/IMD) is a new member of the calcitonin/calcitonin gene-related peptide (CGRP) family. CGRP, adrenomedullin (AM), and AM2/IMD share the receptor system consisting of calcitonin receptor-like receptor (CRLR) and receptor activity-modifying proteins (RAMP). The CRLR/RAMP2 or CRLR/RAMP3 complex forms the AM receptor, whereas the CRLR/RAMP1 forms the CGRP receptor. AM2/IMD binds non-selectively to all three CRLR/RAMP complexes. AM2/IMD has various actions, such as a potent vasodilator action and a protective action against oxidative stress, like AM and CGRP. When administered intracerebroventricularly, AM2/IMD stimulates the sympathetic nervous system and increases blood pressure. In human hypothalamus, AM2/IMD is expressed in the paraventricular and supraoptic nuclei and colocalized with arginine vasopressin. Anterior pituitary cells were diffusely immunostained for AM2/IMD. AM2/IMD stimulates the release of ACTH, prolactin, and oxytocin, but suppresses GH release. Some of these pituitary actions of AM2/IMD have been supposed to be mediated by an unidentified unique receptor for AM2/IMD. In the adrenal gland, immunoreactive (IR)-AM2/IMD and IR-AM were detected in the medulla, while the degree of IR-AM2/IMD and IR-AM in the cortex was relatively weak or undetectable. Furthermore, AM2/IMD and AM were expressed in adrenocortical tumors, such as aldosterone-secreting adenomas, and pheochromocytomas. CRLR and RAMPs are expressed in the hypothalamus, pituitaries, adrenal glands, and adrenal tumors. Thus, AM2/IMD is expressed in every endocrine organ of the hypothalamo-pituitary-adrenal axis together with its receptor. AM2/IMD may act as a neurotransmitter or modulator in the brain and as a paracrine/autocrine regulator in the hypothalamo-pituitary-adrenal axis.

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“…, 1998), we hypothesized that U‐37883A might be inhibiting AM‐induced renin release. Thus, while it has been suggested that AM might be a functional antagonist of AII (Charles et al. , 2000), it was feasible that the observed augmentation of AM‐mediated renal and mesenteric vasodilatations seen following treatment with U‐37883A, was due to a decrease in renin activity and the consequent diminution of the vasoconstrictor effects of AII.…”

Section: Discussionmentioning

confidence: 99%

“…As U-37883A has been shown to inhibit renin release (Humphrey and Ludens, 1998;Vallon et al, 1998), we hypothesized that U-37883A might be inhibiting AM-induced renin release. Thus, while it has been suggested that AM might be a functional antagonist of AII (Charles et al, 2000), it was feasible that the observed augmentation of AM-mediated renal and mesenteric vasodilatations seen following treatment with U-37883A, was due to a decrease in renin activity and the consequent diminution of the vasoconstrictor effects of AII. To test this hypothesis, a separate group of animals was pre-treated with the AT 1 receptor antagonist, losartan, and subsequently given AM and IMD.…”

Section: Intermedin and Adrenomedullin In Vivo L Jolly Et Almentioning

confidence: 99%

Mechanisms involved in the regional haemodynamic effects of intermedin (adrenomedullin 2) compared with adrenomedullin in conscious rats

Jolly

March

Kemp

et al. 2009

British J Pharmacology

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Background and purpose: Intermedin (IMD) is a newly identified member of the calcitonin family of peptides that shares structural and functional homology with adrenomedullin (AM). In vivo cardiovascular effects of AM have been described, but relatively little is known of the in vivo actions of IMD. The purpose of this study was to compare the regional haemodynamic effects of IMD with those of AM in conscious rats, and investigate possible underlying mechanisms. Experimental approach: Measurements of blood pressure, heart rate and renal, mesenteric and hindquarters haemodynamics were made in conscious, chronically-instrumented rats. Key results: IMD caused tachycardia and vasodilatation in all three vascular beds, associated with modest hypotension. At an equimolar dose (1 nmol·kg ), but inhibition of NO synthase was more effective at reducing the vasodilator effects of IMD than AM. Vascular KATP channel blockade with U-37883A did not inhibit the vasodilator effects of either peptide. Conclusions and implications:In vivo, the regional haemodynamic profile of IMD resembles that of AM, and some of the vasodilator effects of IMD are mediated by AM receptors and NO, but not by KATP channels. The cardiovascular effects of AM have been implicated in various pathological conditions, but whether or not endogenous IMD fulfils a similar role remains to be determined.

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Adrenomedullin 2 attenuates the pressor but not adrenal responses to angiotensin II in conscious sheep

Cited by 4 publications

References 37 publications

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

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

Adrenomedullin 2/Intermedin in the Hypothalamo–Pituitary–Adrenal Axis

Mechanisms involved in the regional haemodynamic effects of intermedin (adrenomedullin 2) compared with adrenomedullin in conscious rats

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