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This study tested the hypothesis that (pyr)apelin-13 dose-dependently augments myocardial contractility and coronary blood flow, irrespective of changes in systemic hemodynamics. Acute effects of intravenous (pyr)apelin-13 administration (10 to 1,000 nM) on blood pressure, heart rate, left ventricular pressure and volume, and coronary parameters were measured in dogs and pigs. Administration of (pyr)apelin-13 did not influence blood pressure ( P = 0.59), dP/d t max  ( P = 0.26), or dP/d t min  ( P = 0.85) in dogs. However, heart rate dose-dependently increased &gt; 70% ( P &lt; 0.01), which was accompanied by a significant increase in coronary blood flow ( P &lt; 0.05) and reductions in left ventricular end-diastolic volume and stroke volume ( P &lt; 0.001). In contrast, (pyr)apelin-13 did not significantly affect hemodynamics, coronary blood flow, or indexes of contractile function in pigs. Furthermore, swine studies found no effect of intracoronary (pyr)apelin-13 administration on coronary blood flow ( P = 0.83) or vasorelaxation in isolated, endothelium-intact ( P = 0.89) or denuded ( P = 0.38) coronary artery rings. Examination of all data across (pyr)apelin-13 concentrations revealed an exponential increase in cardiac output as peripheral resistance decreased across pigs and dogs ( P &lt; 0.001; R 2  = 0.78). Assessment of the Frank-Starling relationship demonstrated a significant linear relationship between left ventricular end-diastolic volume and stroke volume across species ( P &lt; 0.001; R 2  = 0.70). Taken together, these findings demonstrate that (pyr)apelin-13 does not directly influence myocardial contractility or coronary blood flow in either dogs or pigs.    NEW &amp; NOTEWORTHY Our findings provide much needed insight regarding the pharmacological cardiac and coronary effects of (pyr)apelin-13 in larger animal preparations. In particular, data highlight distinct hemodynamic responses of apelin across species, which are independent of any direct effect on myocardial contractility or perfusion.

Distinct hemodynamic responses to (pyr)apelin-13 in large animal models