Propofol attenuates angiotensin II-induced vasoconstriction by inhibiting Ca2+-dependent and PKC-mediated Ca 2+ sensitization mechanisms.
OBJECTIVE
Angiotensin II (Ang II)-induced vascular contraction is mediated by Ca(2+)-dependent mechanisms and Ca(2+) sensitization mechanisms. The phosphorylation of protein kinase C (PKC) regulates myofilament Ca(2+) sensitivity. We have previously demonstrated that sevoflurane inhibits Ang II-induced vasoconstriction by inhibiting PKC phosphorylation, whereas isoflurane inhibits Ang II-induced vasoconstriction by decreasing intracellular Ca(2+) concentration ([Ca(2+)](i)) in vascular smooth muscle. Propofol also induces vasodilation; however, the effect of propofol on PKC-mediated myofilament Ca(2+) sensitivity is poorly understood. The aim of this study is to determine the mechanisms by which propofol inhibits Ang II-induced vascular contraction in rat aortic smooth muscle.


METHODS
An isometric force transducer was used to investigate the effect of propofol on vasoconstriction, a fluorometer was used to investigate the change in [Ca(2+)](i), and Western blot testing was used to analyze Ang II-induced PKC phosphorylation.


RESULTS
Ang II (10(-7) M) elicited a transient contraction of rat aortic smooth muscle, which was associated with an elevation of [Ca(2+)](i). Propofol (10(-6 )M) inhibited Ang II-induced vascular contraction (P < 0.01) and increase in [Ca(2+)](i) (P < 0.05) in rat aortic smooth muscle. Ang II also induced a rapid increase in [Ca(2+)](i) in cultured vascular smooth muscle cells, which was suppressed by propofol (P < 0.05). Propofol (10(-6) M) attenuated Ang II-stimulated PKC phosphorylation (P < 0.05).


CONCLUSIONS
These results suggest that the inhibitory effect of propofol on Ang II-induced vascular contraction is mediated by the attenuation of a Ca(2+)-dependent pathway and Ca(2+) sensitivity through the PKC signaling pathway.
Department of Anesthesiology, Wakayama Medical University, 811-1 Kimiidera, Wakayama, 641-0012, Japan.
Toshiyuki
T
Kuriyama
Yasuyuki
Y
Tokinaga
Kazuaki
K
Tange
Yoshiki
Y
Kimoto
Koji
K
Ogawa
D018686:Anesthetics, Intravenous / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D004347:Drug Interactions; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D009210:Myofibrils / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D015742:Propofol / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors* / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects*
D018686:Anesthetics, Intravenous; D000804:Angiotensin II; D011493:Protein Kinase C; D002118:Calcium; D015742:Propofol