REN and heart failure: Clinical studies in healthy volunteers confirm apelin-induced vasodilatation to be dependent on nitric oxide.17 Systemic infusion of [Pyr1]apelin-13 leads to a ∼5% reduction in blood pressure and a fall in peripheral vascular resistance in health and heart failure.39,67 Importantly, apelin promotes vasodilatation even in the setting of renin-angiotensin system activation,39 and circulating concentrations of apelin are lower in patients with hypertension.68–70 There is no clinical evidence of apelin-induced vasoconstriction in health or disease.17,39,67,71,72