cyclic-gmp and apelin-13-peptide

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.

Topics: Adrenocorticotropic Hormone; Aldosterone; Animals; Arginine Vasopressin; Atrial Natriuretic Factor; Blood Pressure; Cardiac Output; Cyclic AMP; Cyclic GMP; Dose-Response Relationship, Drug; Female; Heart Block; Heart Rate; Hemodynamics; Homeostasis; Hormones; Hydrocortisone; Intercellular Signaling Peptides and Proteins; Kidney; Models, Animal; Natriuretic Peptide, Brain; Sheep; Stimulation, Chemical; Vascular Resistance