Responses to propofol in the pulmonary vascular bed of the rat.
BACKGROUND
Although a great deal is known about responses to propofol, controversy remains about its mechanism of action. The present study was undertaken to investigate the direct effects of 2,6-diisopropyl phenol, disodium edetate, and its intralipid emulsion in the rat pulmonary vascular bed and to better understand the mechanisms involved in propofol-mediated responses.


METHODS
The effects of N omega-l-nitro-l-arginine benzyl ester (L-NABE), an inhibitor of nitric oxide synthase, of the cyclooxygenase blocker, meclofenamate, and the K + ATP channel antagonist, U-37883A, an ATP-sensitive potassium channel antagonist, on responses to propofol, acetylcholine, nitroglycerin, and isoproterenol were investigated in the isolated blood-perfused rat lung under low tone and high steady-state tone.


RESULTS
Propofol produced a dose-dependent decrease in pulmonary arterial perfusion pressure. L-NABE significantly reduced vasodilator responses to acetylcholine, whereas the nitric oxide synthase inhibitor had no significant effect on responses to propofol. Meclofenamate significantly reduced vasodilator responses to arachidonic acid without effecting responses to propofol. Responses to propofol were not significantly changed in the presence of U-37883A, whereas U-37883A reduced vasodilator responses to levcromakalim. Additionally, 2,6-diisopropylphenol in a pure preparation as well as an intralipid preparation similar to propofol emulsion had no significant effect while disodium edetate had a dose-dependent depressor effect under high steady-state tone.


CONCLUSIONS
Propofol has significant vasodilator activity in the pulmonary vascular bed of the rat but responses to propofol are not mediated or modulated by the release of nitric oxide, opening of K + ATP channels, or the release of vasodilator cyclooxygenase products.
Kaye
A D
AD
Kaye
A
A
Department of Anesthesiology and Pharmacology, Tulane University Medical School, New Orleans, Louisiana, USA.
Anwar
M
M
Banister
R E
RE
Banister
R
R
Feng
C J
CJ
Feng
C
C
Turner
K
K
Kadowitz
P J
PJ
Kadowitz
P
P
Nossaman
B D
BD
Nossaman
B
B
D000109:Acetylcholine / Q000494:pharmacology; D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000037:antagonists & inhibitors; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D018686:Anesthetics, Intravenous / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002614:Chelating Agents / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004121:Dimethyl Sulfoxide / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007545:Isoproterenol / Q000494:pharmacology; D008168:Lung / Q000098:blood supply* / Q000187:drug effects; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D005996:Nitroglycerin / Q000494:pharmacology; D026902:Potassium Channel Blockers; D015742:Propofol / Q000494:pharmacology*; D011652:Pulmonary Circulation / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012997:Solvents / Q000494:pharmacology; D014665:Vasodilator Agents / Q000494:pharmacology
D000318:Adrenergic beta-Agonists; D018686:Anesthetics, Intravenous; D002614:Chelating Agents; D016861:Cyclooxygenase Inhibitors; D004232:Diuretics; D004791:Enzyme Inhibitors; D009025:Morpholines; D026902:Potassium Channel Blockers; D012997:Solvents; D014665:Vasodilator Agents; D016718:Arachidonic Acid; D008469:Meclofenamic Acid; C082658:U 37883A; C071057:N(w)-nitroarginine benzyl ester; D000255:Adenosine Triphosphate; D001120:Arginine; D004492:Edetic Acid; D019001:Nitric Oxide Synthase; D005996:Nitroglycerin; D007545:Isoproterenol; D000109:Acetylcholine; D000218:Adamantane; D015742:Propofol; D004121:Dimethyl Sulfoxide