Biomaterial Database

Direct cardiac and vascular actions of adrenomedullin in conscious sheep. 1997

D G Parkes, and C N May

Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville VIC, Australia.

1. Adrenomedullin (ADM) is a recently characterized circulating hormone which affects haemodynamic, renal and pituitary function in mammals. We have shown previously that in sheep, ADM produces vasodilatation together with increases in cardiac output and contractility. However, whether these effects are direct or mediated by autonomic reflexes is unclear. The present study examined the cardiovascular actions of an intravenous infusion of ADM in conscious, chronically instrumented sheep with either sympathetic, parasympathetic or autonomic ganglion blockade, to determine the role of the autonomic nervous system in mediating these cardiovascular changes. 2. Human ADM (1-52) was infused for 60 min at 2 micrograms kg-1 h-1 following: (1) saline control, (2) combined alpha/beta-adrenoceptor (sympathetic) blockade (proporanolol 0.4 mg kg-1 h-1 + phentolamine 0.15 mg kg-1 h-1 for 20 h), (3) muscarinic (parasympathetic) blockade (methscopolamine 0.05 mg kg-1 h-1 for 20 h) or (4) ganglion blockade (hexamethonium 3 mg kg-1 h-1 for 4 h). Measurements were made of mean arterial pressure (MAP), heart rate (HR), cardiac output (CO), stroke volume (SV), total peripheral conductance (TPC), maximal aortic flow (Fmax) and maximal rate of change of aortic flow (dF/dt). 3. ADM reduced MAP by 3 +/- 1 mmHg, and increased CO (1.2 +/- 0.2 l min-1), HR (14 +/- 2 beats min-1), TPC (21 +/- 3 ml min-1 mmHg-1). Fmax (2.3 +/- 0.8 l min-1) and dF/dt (86 +/- 21 l min-1 s-1) in normal sheep. In animals with alpha/beta blockade, similar changes were observed with ADM. However, during muscarinic blockade, the increases in HR (32 +/- 4 beats min-1), CO (2.1 +/- 0.4 l min-1), TPC (31 +/- 4 ml min-1 mmHg-1). Fmax (4.0 +/- 0.6 l min-1), and dF/dt (150 +/- 12 l min-1 s-1) produced by ADM were enhanced. During ganglion blockade, ADM produced a greater reduction in MAP (-10 +/- 2 mmHg) compared to controls (-3 +/- 1 mmHg). However, there was no increase in HR. The changes in CO, TPC and contractility were similar to those observed in control animals. 4. These results suggest that the vasodilator effects of ADM on the periphery and its ability to increase CO and cardiac contractility are not mediated by the autonomic nervous system, but are probably the result of direct actions of ADM on the heart and vasculature.

UI	MeSH Term	Description	Entries
D009200	Myocardial Contraction	Contractile activity of the MYOCARDIUM.	Heart Contractility,Inotropism, Cardiac,Cardiac Inotropism,Cardiac Inotropisms,Contractilities, Heart,Contractility, Heart,Contraction, Myocardial,Contractions, Myocardial,Heart Contractilities,Inotropisms, Cardiac,Myocardial Contractions
D010455	Peptides	Members of the class of compounds composed of AMINO ACIDS joined together by peptide bonds between adjacent amino acids into linear, branched or cyclical structures. OLIGOPEPTIDES are composed of approximately 2-12 amino acids. Polypeptides are composed of approximately 13 or more amino acids. PROTEINS are considered to be larger versions of peptides that can form into complex structures such as ENZYMES and RECEPTORS.	Peptide,Polypeptide,Polypeptides
D012083	Renin	A highly specific (Leu-Leu) endopeptidase that generates ANGIOTENSIN I from its precursor ANGIOTENSINOGEN, leading to a cascade of reactions which elevate BLOOD PRESSURE and increase sodium retention by the kidney in the RENIN-ANGIOTENSIN SYSTEM. The enzyme was formerly listed as EC 3.4.99.19.	Angiotensin-Forming Enzyme,Angiotensinogenase,Big Renin,Cryorenin,Inactive Renin,Pre-Prorenin,Preprorenin,Prorenin,Angiotensin Forming Enzyme,Pre Prorenin,Renin, Big,Renin, Inactive
D005260	Female		Females
D005730	Ganglionic Blockers	Agents having as their major action the interruption of neural transmission at nicotinic receptors on postganglionic autonomic neurons. Because their actions are so broad, including blocking of sympathetic and parasympathetic systems, their therapeutic use has been largely supplanted by more specific drugs. They may still be used in the control of blood pressure in patients with acute dissecting aortic aneurysm and for the induction of hypotension in surgery.	Ganglionic Blocking Agents,Ganglioplegic Agents,Blocking Agents, Ganglionic,Ganglionic Blockaders,Agents, Ganglionic Blocking,Agents, Ganglioplegic,Blockaders, Ganglionic,Blockers, Ganglionic
D006439	Hemodynamics	The movement and the forces involved in the movement of the blood through the CARDIOVASCULAR SYSTEM.	Hemodynamic
D006854	Hydrocortisone	The main glucocorticoid secreted by the ADRENAL CORTEX. Its synthetic counterpart is used, either as an injection or topically, in the treatment of inflammation, allergy, collagen diseases, asthma, adrenocortical deficiency, shock, and some neoplastic conditions.	Cortef,Cortisol,Pregn-4-ene-3,20-dione, 11,17,21-trihydroxy-, (11beta)-,11-Epicortisol,Cortifair,Cortril,Epicortisol,Hydrocortisone, (11 alpha)-Isomer,Hydrocortisone, (9 beta,10 alpha,11 alpha)-Isomer,11 Epicortisol
D000324	Adrenocorticotropic Hormone	An anterior pituitary hormone that stimulates the ADRENAL CORTEX and its production of CORTICOSTEROIDS. ACTH is a 39-amino acid polypeptide of which the N-terminal 24-amino acid segment is identical in all species and contains the adrenocorticotrophic activity. Upon further tissue-specific processing, ACTH can yield ALPHA-MSH and corticotrophin-like intermediate lobe peptide (CLIP).	ACTH,Adrenocorticotropin,Corticotropin,1-39 ACTH,ACTH (1-39),Adrenocorticotrophic Hormone,Corticotrophin,Corticotrophin (1-39),Corticotropin (1-39),Hormone, Adrenocorticotrophic,Hormone, Adrenocorticotropic
D000818	Animals	Unicellular or multicellular, heterotrophic organisms, that have sensation and the power of voluntary movement. Under the older five kingdom paradigm, Animalia was one of the kingdoms. Under the modern three domain model, Animalia represents one of the many groups in the domain EUKARYOTA.	Animal,Metazoa,Animalia
D012756	Sheep	Any of the ruminant mammals with curved horns in the genus Ovis, family Bovidae. They possess lachrymal grooves and interdigital glands, which are absent in GOATS.	Ovis,Sheep, Dall,Dall Sheep,Ovis dalli