Propofol increases pulmonary vascular resistance during alpha-adrenoreceptor activation in normal and monocrotaline-induced pulmonary hypertensive rats.
BACKGROUND
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.


METHODS
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).


RESULTS
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).


CONCLUSIONS
Propofol may increase pulmonary vascular resistance during alpha-adrenoreceptor activation.
Edanaga
Mitsutaka
M
Department of Anesthesiology,Sapporo Medical University School of Medicine, Sapporo, Hokkaido, Japan. edanaka@sapmed.ac.jp
Nakayama
Masayasu
M
Kanaya
Noriaki
N
Tohse
Noritsugu
N
Namiki
Akiyoshi
A
D000818:Animals; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D016686:Monocrotaline; D015742:Propofol / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000502:physiology*; D051381:Rats; D011918:Rats, Inbred SHR; D017207:Rats, Sprague-Dawley; D011942:Receptors, Adrenergic, alpha / Q000187:drug effects / Q000502:physiology*; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*
D011942:Receptors, Adrenergic, alpha; D016686:Monocrotaline; D015742:Propofol