Role of PKC in isoflurane-induced biphasic contraction in skinned pulmonary arterial strips.
BACKGROUND
Activation or inhibition of protein kinase C (PKC) has been implicated in the anesthetic-induced contraction or relaxation of different types of arteries. In skinned pulmonary arterial strips, the initial halothane-induced contraction has been attributed to PKC activation, but the subsequent relaxation has not. Whether isoflurane has a similar biphasic effect is not known. This study examined the role of PKC and its isoforms in the effect of isoflurane on pulmonary artery.


METHODS
Rabbit pulmonary arterial strips were mounted on force transducers and treated with saponin to make the sarcolemma permeable ("skinned" strips). Skinned strips were activated by low Ca(2+) (pCa 6.5 or pCa 6.3 buffered with 7 mm EGTA) or the PKC activator phorbol-12,13-dibutyrate (1 microm) until force reached a steady state (control). Various concentrations of isoflurane (test) were administered, and force was observed at time intervals up to 60 min. The PKC inhibitors (bisindolylmaleimide and Go6976 from 0.1 to 10 microm) were preincubated in a relaxing solution and the subsequent contracting solutions. The results were expressed as a percentage of control, with P < 0.05 considered significant for statistical comparison between the tests and time controls.


RESULTS
In a dose-dependent fashion, isoflurane (1-5%) initially increased (5-40%) and then decreased (3-70%) the Ca(2+)- or phorbol-12,13-dibutyrate (pCa 6.7 buffer)-activated force. The increased in force caused by isoflurane was partially reduced by 3 and 10 microm bisindolylmaleimide, but not by Go6976. Isoflurane-induced relaxation was partially prevented by both inhibitors at 0.1 and 0.3 microm.


CONCLUSIONS
Isoflurane causes biphasic effects in skinned pulmonary arterial strips that may be in part mediated by different isoforms of PKC.
Su
Judy Y
JY
Department of Anesthesiology, University of Washington, Seattle, 98195-6540, USA. jsu@u.washington.edu
Vo
Anhkiet C
AC
D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D007211:Indoles / Q000494:pharmacology; D007527:Isoenzymes / Q000502:physiology; D007530:Isoflurane / Q000494:pharmacology*; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D020928:Mitogen-Activated Protein Kinases / Q000502:physiology; D018994:Myosin Light Chains / Q000502:physiology; D009219:Myosin-Light-Chain Kinase / Q000502:physiology; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D011651:Pulmonary Artery / Q000187:drug effects* / Q000201:enzymology / Q000502:physiology; D011817:Rabbits; D014661:Vasoconstriction / Q000187:drug effects*
D018685:Anesthetics, Inhalation; D004791:Enzyme Inhibitors; D007211:Indoles; D007527:Isoenzymes; D008301:Maleimides; D018994:Myosin Light Chains; D010703:Phorbol Esters; C008874:phorbol-12,13-diacetate; D007530:Isoflurane; D011493:Protein Kinase C; D009219:Myosin-Light-Chain Kinase; D020928:Mitogen-Activated Protein Kinases; C088060:bisindolylmaleimide; D002118:Calcium