Orthostatic Stimuli Rapidly Change Plasma Adrenomedullin in Humans

Abstract

Abstract-The aim of this study was to evaluate the effect of orthostasis on the time course of plasma adrenomedullin concentration. On 5 different days, normotensive subjects were randomized to undergo for 30 minutes either 12°, 30°, 53°, or 70°passive head-up tilt or to remain supine. Venous blood was collected from each subject in the supine position before tilting, at 3 and 27 minutes during tilting, and at 2 and 50 minutes after orthostasis. Plasma adrenomedullin increased significantly with tilt of Ն30°in a stimulus-dependent manner. Approximately half of the increase seen at 27 minutes occurred during the first 2 minutes of upright positioning; the maximum effect with 70°tilt was ϩ70%. Elevations in norepinephrine, epinephrine, aldosterone, plasma renin activity, vasopressin, heart rate, and mean arterial pressure were also significant. Hematocrit, blood density, plasma density, and plasma volume loss rose (PϽ0.05) at 53°a nd 70°tilt. Our results indicate that adrenomedullin may play an important role in stabilization of hemodynamics during passive orthostasis. In conclusion, plasma adrenomedullin rapidly increases with orthostatic challenge in a stimulus-dependent manner and also swiftly returns to baseline levels after the subject resumes the supine position. Key Words: tilt, head-up Ⅲ adrenomedullin Ⅲ barorereflex Ⅲ volume, plasma Ⅲ catecholamines T he 52-amino acid peptide adrenomedullin (ADM) is a potent vasorelaxant 1 and natriuretic 2 peptide. The strong relationship between plasma ADM and vascular tone functions in water homeostasis by increasing the glomerular filtration rate and natriuresis while lessening renal vascular resistance. 2,3 Additionally, ADM might function as an endothelium-derived relaxation factor and an autocrine or paracrine factor for vascular smooth muscle. 4 Until now, no data were available on changes in plasma ADM levels induced by orthostasis, which redistributes blood from central-to lower-body vascular beds and unloads cardiopulmonary receptors 5 ; this causes constriction of resistance and capacitance vessels, 6 in part through the action of vasopressin, angiotensin, and endothelin-1. 7,8 The present investigation was designed to test the hypothesis that plasma ADM is influenced by head-up tilting (HUT) in normotensive, euhydrated humans; to study the time course of ADM during and after HUT; and to quantify effects in relation to the intensity of orthostatic challenge. As ancillary information, hemodynamic and other endocrine as well as blood volume indicators were determined. The present study shows that ADM responds quickly and in a dose-dependent manner to HUT, and its concentration rapidly declines afterward.

The role of adrenomedullin and galanin in recurrent vasovagal syncope: a case control study

“…This advocates the role of ADM in a failed prevention of a syncope by excessive paradoxical vasodilatation in healthy individuals and the supression of this effect by nitroglycerin administration. Our results show an increasing trend in ADM levels in healthy individuals during HUTT which partly supports Rossler et al 4 . Although a different protocol and tilt angle were used Nishikimi et al 18 failed to demonstrate ADM increase after 20 min of 70° HUTT in healthy volunteers.…”

“…No significant change in ADM plasma levels was observed in our trial, although there was a slight increase in ADM plasma levels in healthy individuals with a positive response to HUTT. It was shown that ADM plasma levels increased significantly with tilting and this correlated with the tilt table inclination level in healthy individuals 4 . Similar results were reported by Gajek et al 15 , who demonstrated increased ADM plasma levels during HUTT immediately after syncope in patients with vasovagal vasodepresor reaction.…”

“…Both peptides are known to affect vasovagal response. However, their specific roles are unclear 3,4 . Thus the rationale of this study was to ascertain whether either one or both peptides are substantially involved in the course of VVS.…”

“…ADM is constitutively produced by endothelial cells and regulated on the level of gene expression 12 . It has been reported that the ADM plasma levels increase during the head-up tilt test (HUTT) -induced passive orthostasis -followed by a decrease after supination 4 . In the present study, we investigated whether the secretion patterns of GAL and ADM during HUTT differ in patients suffering from recurrent vasovagal syncope (rVVS) and for healthy individuals.…”

Adrenomedullin and diabetes mellitus

“…Its level rapidly changes during and after various degrees of passive head up tilt in normotensive humans, which suggests quick and sensitive baroreceptor-driven secretion. AM seems to play an important role in cardiovascular stability in concert with other humoral mechanisms [17]. Under pathological conditions, for example in primer hyperaldosteronism and in hypertension, parallel to the severity of the disease the plasma level of AM increases [18][19][20].…”