title: Apelin-13 induces a biphasic haemodynamic response and hormonal activation in normal conscious sheep.
abstract: Whilst the tissue distribution and range of biological actions reported for apelin suggest a role for the peptide in pressure/volume homeostasis, conflicting reports make the precise role unclear. Furthermore, few integrated studies have been performed and there are no reports of bioactivity of apelin in a large animal model. Accordingly, we have examined the haemodynamic, hormonal and renal effects of apelin in ten normal conscious sheep. Apelin (1 mg i.v. bolus) induced a biphasic haemo-dynamic response characterised by an acute fall in arterial pressure and a rise in heart rate followed immediately by a rise in arterial pressure and a fall in heart rate. The secondary hypertensive phase was associated with a fall in cardiac output (P=0.015) and significant rises in calculated total peripheral resistance (CTPR) (P<0.001) and right atrial pressure (RAP) (P=0.031). Electrocardiogram changes were also observed in four of ten sheep, most notably varying degrees of atrioventricular block. Apelin also induced significant rises in plasma arginine vasopressin (P=0.009), adrenocorticotrophin (P=0.012), aldosterone (P=0.001), cortisol (P=0.014), atrial (P=0.036) and brain (P<0.001) natriuretic peptide, cyclic GMP (P=0.003) and cyclic AMP (P=0.002) levels with no effect on renal indices. In conclusion, high dose administration of apelin to normal conscious sheep induces a significant biphasic response in arterial pressure and heart rate associated with rises in RAP and CTPR and a fall in cardiac output. Apelin also increases circulating levels of a number of vasoactive hormones. Taken together, these results suggest a potential role for apelin in pressure/volume homeostasis.
authors.affiliation: Christchurch Cardioendocrine Research Group, Christchurch School of Medicine and Health Sciences, Christchurch, New Zealand. chris.charles@chmeds.ac.nz
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: Charles
authors.forename: Miriam T
authors.initials: MT
authors.lastname: Rademaker
authors.forename: A Mark
authors.initials: AM
authors.lastname: Richards
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000450:Aldosterone / Q000097:blood; D000818:Animals; D001127:Arginine Vasopressin / Q000097:blood; D009320:Atrial Natriuretic Factor / Q000097:blood; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output; D000242:Cyclic AMP / Q000097:blood; D006152:Cyclic GMP / Q000097:blood; D004305:Dose-Response Relationship, Drug; D005260:Female; D006327:Heart Block / Q000139:chemically induced; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006706:Homeostasis / Q000187:drug effects; D006728:Hormones / Q000378:metabolism*; D006854:Hydrocortisone / Q000097:blood; D036341:Intercellular Signaling Peptides and Proteins / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects; D023421:Models, Animal; D020097:Natriuretic Peptide, Brain / Q000097:blood; D012756:Sheep; D013268:Stimulation, Chemical; D014655:Vascular Resistance / Q000187:drug effects
chemical_list: D006728:Hormones; D036341:Intercellular Signaling Peptides and Proteins; C495199:apelin-13 peptide; D001127:Arginine Vasopressin; D020097:Natriuretic Peptide, Brain; D000450:Aldosterone; D009320:Atrial Natriuretic Factor; D000324:Adrenocorticotropic Hormone; D000242:Cyclic AMP; D006152:Cyclic GMP; D006854:Hydrocortisone