Adrenomedullin and the Control of Fluid and Electrolyte Homeostasis

Abstract

▪ Abstract Two potent hypotensive peptides, adrenomedullin (AM) and proadrenomedullin N-terminal 20 peptide (PAMP), are encoded by the adrenomedullin gene. AM stimulates nitric oxide production by endothelial cells, whereas PAMP acts presynaptically to inhibit adrenergic nerves that innervate blood vessels. Complementary, but mechanistically unique, actions also occur in the anterior pituitary gland where both peptides inhibit adrenocorticotropin release. In the adrenal gland both AM and PAMP inhibit potassium and angiotensin II-stimulated aldosterone secretion. Natriuretic and diuretic actions of AM reflect unique actions of the peptide on renal blood flow and tubular function. In the brain AM inhibits water intake and, in a physiologically relevant manner, salt appetite. Both AM and PAMP act in the brain to elevate sympathetic tone, effects that mirror the positive inotropic action of AM in the heart. Cardioprotective actions in the brain and heart may be important counter-regulatory actions that buffer the extreme hypotensive actions of the peptides when released in sepsis. Thus the biologic actions of the proadrenomedullin-derived peptides seem well coordinated to contribute to the physiologic regulation of volume and electrolyte homeostasis.

Long-Term Adrenomedullin Administration in Experimental Heart Failure

“…Alternatively, other signaling pathways were involved. 1 Similar to studies using acute administration of AM, 8 plasma levels of the natriuretic peptides were unaltered compared with control data during the first 6 hours of the AM infusion period, despite significant falls in LAP and therefore the stimulus for secretion. These findings contrast with previous investigations in which short-term administration of vasodilator agents such as ACE inhibitors demonstrate a close parallelism between falls in atrial pressure and plasma natriuretic peptides levels.…”

“…AM is detected in a wide variety of tissues, 1 and measurable levels circulate in normal human plasma (typically in the lower picomolar range). 2 In heart failure (HF), cardiac production and secretion of AM are increased, 3,4 and plasma levels of the peptide are elevated in proportion to the severity of cardiac and hemodynamic impairment.…”

Adrenomedullin increases cardiac sympathetic nerve activity in normal conscious sheep

“…NP is a nitric oxide donor and therefore has a rapid onset and short duration of action, acts equally on all vascular beds, and probably does not cross the blood-brain barrier (Friederich & Butterworth 1995). In contrast, AM acts via its own receptors, has a longer duration of action, effects only some vascular beds, and may have direct effects on the central nervous system (Samson 1999). Furthermore, NP is predominantly a venodilator and has no direct inotropic effect, both of which limit the cardiac output response to hypotension (Miletich & Ivankovich 1978, Bauer & Fung 1996.…”

“…Adrenomedullin (AM) is a 52 amino acid peptide also involved in the regulation of vascular tone and pressure/volume homeostasis (Samson 1999). Both entities show enhanced activation in cardiac injury and in heart failure, but the interaction between AM and the sympathetic nervous system is uncertain.…”

Adrenomedullin Antagonist Infusion Causes Uteroimplantation Growth Restriction

“…[1] The first paper on adrenomedullin, published by (Kitumara et al, 1993 date including a number of reviews. [2][3][4][5][6][7] This review aims to summarize the present state of our knowledge of adrenomedullin biology and to focus on issues that are currently unresolved, with an indication of likely areas for future research.…”