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

Background: 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). Methods: PASMCs were cultured from explants of canine intrapulmonary artery. Fura-2-loaded PASMCs mere continuously superfused with phenylephrine (10 mu M) 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. Results: 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 mu M) reduced the amplitude (221 +/- 22 nM) but not the frequency (1.48 +/- 0.11/min) of the oscillations, whereas thiopental (100 mu M) decreased the amplitude (270 +/- 20 nM) and the frequency (1.04 +/- 0.10/min). Propofol (100 mu M) and the Intralipid(R) 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. Conclusion: 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.