Adrenomedullin modulates the neurohumoral response to acute volume loading in normal conscious sheep

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

doi:10.1677/joe.0.1730123

Cited by 8 publications

(7 citation statements)

References 28 publications

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“…These levels are at the upper limit of the physiological range in sheep and similar to those seen with acute dextran loading in normal sheep (12). The achieved plasma levels of ANP and BNP are also well within pathophysiological levels observed in heart failure in both a sheep model (26) and humans (27).…”

Section: Discussionsupporting

confidence: 75%

Low-dose B-type natriuretic peptide raises cardiac sympathetic nerve activity in sheep

Charles

Jardine

Rademaker

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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The reported effects of atrial natriuretic peptide (ANP) on sympathetic nerve activity (SNA) are variable, dependent on concomitant hemodynamic actions, and likely to be regionally differentiated. There are few reports of the effect of B-type natriuretic peptide (BNP) on SNA and none have measured cardiac SNA (CSNA) by direct microneurography. We measured the effects of low-dose ANP and BNP (2.4 pmol·kg(-1)·min(-1) infused for 120 min) on CSNA and hemodynamics in conscious sheep (n = 8). While there was a trend for mean arterial pressure and cardiac output to fall with both ANP and BNP, changes were not significant compared with vehicle control. However, BNP did significantly reduce systolic arterial (97 ± 4.2 vs. 107 ± 6.8 mmHg during control; P = 0.043) and pulse pressures (0.047) and increase heart rate (110 ± 6.7 vs. 96 ± 7.3 beats/min; P = 0.044). Trends for these hemodynamic parameters to change with ANP did not achieve statistical significance. ANP also had no significant effect on any CSNA parameters measured. In contrast, BNP induced a rise in both CSNA burst frequency (∼20 bursts/min higher than control, P = 0.011) and burst area (∼40% higher than control, P = 0.013). BNP-induced rises in burst incidence (bursts/100 beats), and burst area per 100 beats, however, were not significant. In conclusion, BNP infused at low doses that only had subtle effects on hemodynamics increased CSNA burst frequency and burst are per minute. This increase in CSNA may in large part be secondary to an increase in heart rate as CSNA burst incidence and burst area per 100 beats were not significantly increased. This study provides no evidence for inhibition of CSNA by natriuretic peptides.

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Section: Discussionsupporting

confidence: 75%

Low-dose B-type natriuretic peptide raises cardiac sympathetic nerve activity in sheep

Charles

Jardine

Rademaker

et al. 2014

American Journal of Physiology-Regulatory, Integrative and Comp

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“…Furthermore, in those studies, plasma ANP and BNP levels increase significantly post AM infusion concurrent with filling pressures returning to baseline levels. AM also enhances the ANP response to acute volume loading in normal sheep (33). The reason for the predominantly delayed accentuation of natriuretic peptides by AM-2 is not clear.…”

Section: Discussionmentioning

confidence: 92%

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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“…Earlier studies have established that AM induces an increase in cardiac output in both rat and sheep (4,20). Increased …”

Section: Discussionmentioning

confidence: 98%

Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats

Luodonpää¹

2004

American Journal of Physiology-Regulatory, Integrative and Comp

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Luodonpää, Marja, Hanna Leskinen, Mika Ilves, Olli Vuolteenaho, and Heikki Ruskoaho. Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats. Am J Physiol Regul Integr Comp Physiol 286: R1085-R1092, 2004. First published January 29, 2004 10.1152/ajpregu.00726.2003.-We examined whether adrenomedullin, a vasoactive peptide expressed in the heart, modulates the increase in blood pressure, changes in systolic and diastolic function, and left ventricular hypertrophy produced by long-term administration of ANG II or norepinephrine in rats. Subcutaneous administration of adrenomedullin (1.5 g ⅐ kg Ϫ1 ⅐ h Ϫ1 ) for 1 wk inhibited the ANG II-induced (33.3 g ⅐ kg Ϫ1 ⅐ h Ϫ1 sc) increase in mean arterial pressure by 67% (P Ͻ 0.001) but had no effect of norepinephrine-induced (300 g⅐kg Ϫ1 ⅐h Ϫ1 sc) hypertension. Adrenomedullin enhanced the ANG II-induced improvement in systolic function, resulting in a further 9% increase (P Ͻ 0.01) in the left ventricular ejection fraction and 19% increase (P Ͻ 0.05) in the left ventricular fractional shortening measured by echocardiography, meanwhile norepinephrine-induced changes in systolic function were remained unaffected. Adrenomedullin had no effect on ANG II-or norepinephrine-induced left ventricular hypertrophy or expression of hypertrophy-associated genes, including contractile protein and natriuretic peptide genes. The present study shows that adrenomedullin selectively suppressed the increase in blood pressure and augmented the improvement of systolic function induced by ANG II. Because adrenomedullin had no effects on ANG II-and norepinephrine-induced left ventricular hypertrophy, circulating adrenomedullin appears to act mainly as a regulator of vascular tone and cardiac function.catecholamines; hypertrophy; ventricular function CARDIAC HYPERTROPHY is a physiological process adapting the heart to an increased hemodynamic workload. Initially, hypertrophy is a compensatory mechanism but eventually leads to pathologic myocyte hypertrophy characterized by increase in cell size, enhanced sarcomeric organization, and induction of the fetal gene program (14). Experimental and clinical evidence suggests that ANG II has an important role in cardiac and vascular pathology and that under some circumstances the renin-angiotensin system (RAS) is a predominant factor in development of left ventricular hypertrophy (LVH) (7). Also adrenergic signaling via sympathetic nervous system may play an important role in the adaptation of the heart to pressure and volume overload (14) and LVH is often associated with an increase in intracardiac sympathetic nerve activity and elevated plasma catecholamines (1).Recently, several reports have suggested a role for adrenomedullin (AM) in paracrine and/or autocrine regulation of cardiac function and myocyte growth. High levels of AM mRNA (28) and 125 I-labeled AM binding sites (23) have been identified in the heart. Both circulating immunoreactive (ir)-AM concentrations and cardiac AM mRNA levels increase in heart failur...

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Adrenomedullin modulates the neurohumoral response to acute volume loading in normal conscious sheep

Cited by 8 publications

References 28 publications

Low-dose B-type natriuretic peptide raises cardiac sympathetic nerve activity in sheep

Low-dose B-type natriuretic peptide raises cardiac sympathetic nerve activity in sheep

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

Adrenomedullin modulates hemodynamic and cardiac effects of angiotensin II in conscious rats

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