Propofol Increases Pulmonary Vascular Resistance During ??-Adrenoreceptor Activation in Normal and Monocrotaline-Induced Pulmonary Hypertensive Rats

Abstract

Using isolated perfused lungs of normal or monocrotaline (MCT: 50 mg/kg)-induced pulmonary hypertensive rats, we tested the hypothesis that the pulmonary vascular effects of propofol depend on activation of the alpha-adrenoreceptor. Changes in pulmonary perfusion pressure induced by propofol (10(-5) to 10(-4) M) were measured with or without phenylephrine (10(-6) M) pretreatment. Before phenylephrine administration, we assessed the effects of inhibitors of nitric oxide synthase (N(omega)-nitro-l-arginine methylester: 10(-4) M), cyclooxygenase (indomethacin: 10(-5) M), and protein kinase C inhibitor, bisindolylmaleimide I (10(-6) M) or calphostin C (10(-6) M). Changes in pulmonary perfusion pressure by phenylephrine after pretreatment of nitric oxide synthase inhibitor and indomethacin in normal rats were significant (5 +/- 3 and 7 +/- 2 mm Hg), whereas that after pretreatment of bisindolylmaleimide I were small in MCT-rats (2 +/- 1 mm Hg). Propofol caused pulmonary vasoconstriction after phenylephrine pretreatment both in normal and MCT-treated rats. In normal rats, the propofol-induced increase in pulmonary perfusion pressure after indomethacin pretreatment was slightly smaller than that in the non-pretreated lungs (P < 0.05). In MCT-treated rats, the propofol-induced increases in pulmonary perfusion pressure after both protein kinase C inhibitors were smaller than that in the non-pretreated lungs (P < 0.05). Propofol may increase pulmonary vascular resistance during alpha-adrenoreceptor activation.