Role of Na+/phosphate-cotransporter in myocardial contractile responses to alpha 1-agonist.

The interaction of cardiac sodium/phosphate (Na+/Pi)-cotransporter and the phosphoinositide pathway (PIP) in influencing myocardial contraction was investigated. Specifically, the study was performed to determine if myocardial positive inotropic response (+dP/dt) to phenylephrine (PE, an activator of PIP) can be potentiated by inorganic phosphate (Pi, the substrate of Na+/Pi-cotransporter). Contractile responses of the isolated perfused rat heart were studied in conditions of controlled extracellular calcium activity and constant preload. The data showed that phenylephrine-induced increase in +dP/dt was potentiated by Pi. Prazosin inhibited this increase in +dP/dt, indicating alpha 1-adrenergic involvement. This Pi-potentiated increase in +dP/dt was also inhibited by phosphonoformate (PFA); however, only partial inhibition was obtained with concentrations of PFA that selectively inhibited Na+/Pi-cotransporter. Isoproterenol-induced increase in +dP/dt was not potentiated by Pi, showing that potentiation of +dP/dt is not a common effect of Pi. The data support an important interaction between PIP and Na+/Pi-cotransporter in regulating myocardial contraction.