Tune, Johnathan D.Baker, Hana E.Berwick, ZacharyMoberly, Steven P.Casalini, Eli D.Noblet, Jillian N.Zhen, EugeneKowala, Mark C.Christe, Michael E.Goodwill, Adam2022-01-282022-01-282020-04Tune, J. D., Baker, H. E., Berwick, Z., Moberly, S. P., Casalini, E. D., Noblet, J. N., Zhen, E., Kowala, M. C., Christe, M. E., & Goodwill, A. G. (2020). Distinct hemodynamic responses to (pyr)apelin-13 in large animal models. American Journal of Physiology. Heart and Circulatory Physiology, 318(4), H747–H755. https://doi.org/10.1152/ajpheart.00365.2019https://hdl.handle.net/1805/27620This 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/dtmax (P = 0.26), or dP/dtmin (P = 0.85) in dogs. However, heart rate dose-dependently increased > 70% (P < 0.01), which was accompanied by a significant increase in coronary blood flow (P < 0.05) and reductions in left ventricular end-diastolic volume and stroke volume (P < 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 < 0.001; R2 = 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 < 0.001; R2 = 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.enPublisher Policyapelinintropycoronary blood flowArticle