Plasma catecholamine and hemodynamic responses during isoproterenol infusions in humans

We infused isoproterenol (ISO) intravenously into 23 subjects (3.5, 7, 14, and 35 ng/kg/min for 20 minutes at each dose) and measured venous plasma concentrations of ISO and the circulatory and plasma norepinephrine (NE) and epinephrine (E) responses. At the lowest dose, venous plasma ISO averaged 48 pg/ml and was associated with increased heart rate (9%; P < 0.001), cardiac index (20%; P < 0.001), and stroke volume (9%; P < 0.02) and decreased total peripheral resistance index (-21%; P < 0.001). Linear concentration-response relationships were observed between plasma ISO and cardiac index and between plasma ISO and heart rate. Plasma NE increased as a function of plasma ISO (mean increase 81% at 35 ng/kg/min), whereas plasma E was unchanged or decreased. The results indicate that circulatory effects of ISO are detectable in humans at plasma concentrations in the range of physiologic levels of E. Since ISO increases plasma NE, ISO may act presynaptically to enhance NE release from sympathetic nerve terminals and thereby stimulate a-adrenoceptors indirectly. ISO does not appear to stimulate secretion from the adrenal medulla or corelease of E with NE from sympathetic nerve endings.