Pulmonary vasodilation by ketamine is mediated in part by L-type calcium channels.
We studied the effects of ketamine in the isolated rat lung under conditions of increased pulmonary arterial pressure using the thromboxane A2 mimic, U46619, and in response to ventilatory hypoxia. Ketamine caused dose-dependent vasodilation, and possible mechanisms were evaluated using verapamil, meclofenamate, N(omega)-L-nitro-L-arginine benzyl ester (an inhibitor of nitric oxide synthase), and U-38883A (an ATP-sensitive potassium channel antagonist) in the isolated blood-perfused rat lung. Under increased tone conditions, N(omega)-L-nitro-L-arginine benzyl ester, meclofenamate, and U-38883A had no significant effect in attenuating ketamine-induced vasodilator responses. In a final series of experiments, verapamil significantly attenuated ketamine-induced vasodilator responses. These data suggest that ketamine has significant vasodilator activity in the pulmonary vascular bed of the rat, which seems to be mediated by an L-type calcium channel-sensitive pathway. These responses are not mediated or modulated by the release of nitric oxide, the activation of K+ ATP channels, or the release of vasodilator cyclooxygenase products.


CONCLUSIONS
In this study, we examined the mechanism of the vasodilator effects of ketamine in the blood-perfused rat lung. The results of the present study suggest that ketamine-induced vasodilator responses are mediated by an L-type calcium channel-sensitive pathway.
Department of Anesthesiology, Tulane University Medical School, New Orleans, Louisiana 70112-2699, USA.
A D
AD
Kaye
R E
RE
Banister
M
M
Anwar
C J
CJ
Feng
P J
PJ
Kadowitz
B D
BD
Nossaman
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology; D000218:Adamantane / Q000031:analogs & derivatives / Q000494:pharmacology; D000778:Anesthetics, Dissociative / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000502:physiology*; D019806:Cromakalim / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D007649:Ketamine / Q000494:pharmacology*; D008168:Lung / Q000098:blood supply; D008297:Male; D008469:Meclofenamic Acid / Q000494:pharmacology; D009025:Morpholines / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects; D011651:Pulmonary Artery / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D014664:Vasodilation / Q000187:drug effects*; D014700:Verapamil / Q000494:pharmacology
D000778:Anesthetics, Dissociative; D002121:Calcium Channel Blockers; D015220:Calcium Channels; D016861:Cyclooxygenase Inhibitors; D009025:Morpholines; D015221:Potassium Channels; D019806:Cromakalim; D016718:Arachidonic Acid; D008469:Meclofenamic Acid; C082658:U 37883A; D007649:Ketamine; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; C071057:N(w)-nitroarginine benzyl ester; D001120:Arginine; D014700:Verapamil; D000218:Adamantane