Intravenous anesthetics attenuate phenylephrine-induced calcium oscillations in individual pulmonary artery smooth muscle cells.

Abstract

The authors investigated the effects of intravenous anesthetics on alpha-adrenergic-induced oscillations in intracellular free calcium concentration ([Ca2+]i) in individual pulmonary artery smooth muscle cells (PASMCs). PASMCs were cultured from explants of canine intrapulmonary artery. Fura-2-loaded PASMCs were continuously superfused with phenylephrine (10 microM) at 37 degrees C on the stage of an inverted fluorescence microscope. Measurement of [Ca2+]i was via a dual wavelength spectrofluorometer. Intravenous anesthetics were added to the superfusate to assess their effects on the phenylephrine-induced [Ca2+]i oscillations. Resting [Ca2+]i was 103 +/- 6 nM. Phenylephrine stimulated [Ca2+]i oscillations, reaching a peak concentration of 632 +/- 20 nM and a frequency of 1.53 +/- 0.14 transients/min. The effects of phenylephrine were dose-dependent. The effects of intravenous anesthetics on phenylephrine-induced [Ca2+]i oscillations were dose-dependent. Ketamine (100 microM) reduced the amplitude (221 +/- 22 nM) but not the frequency (1.48 +/- 0.11/min) of the oscillations, whereas thiopental (100 microM) decreased the amplitude (270 +/- 20 nM) and the frequency (1.04 +/- 0.10/min). Propofol (100 microM) and the Intralipid vehicle inhibited the amplitude (274 +/- 11 nM) but not the frequency (1.39 +/- 0.11/min) of the oscillations. The effects of ketamine and thiopental, but not propofol, were evident at clinically relevant concentrations. Ketamine, thiopental, and propofol exerted differential effects to inhibit the amplitude or the frequency of phenylephrine-induced [Ca2+]i oscillations in individual PASMCs. Thus, intravenous anesthetics may alter the pulmonary vascular response to alpha-adrenoreceptor activation by directly inhibiting [Ca2+]i signaling in PASMCs.