Propofol induces excessive vasodilation of aortic rings by inhibiting protein kinase C?2 and ? in spontaneously hypertensive rats.

ABSTRACT: BACKGROUND AND PURPOSE:Exaggerated hypotension following administration of propofol is strongly predicted in patients with hypertension. Increased PKCs play a crucial role in regulating vascular tone. We studied whether propofol induces vasodilation by inhibiting increased PKC activity in spontaneously hypertensive rats (SHRs) and, if so, whether contractile Ca2+ sensitization pathways and filamentous-globular (F/G) actin dynamics were involved. EXPERIMENTAL APPROACH:Rings of thoracic aorta, denuded of endothelium, from normotensive Wistar-Kyoto (WKY) rats and SHR were prepared for functional studies. Expression and activity of PKCs in vascular smooth muscle (VSM) cells were determined by Western blot analysis and elisa respectively. Phosphorylation of the key proteins in PKC Ca2+ sensitization pathways was also examined. Actin polymerization was evaluated by differential centrifugation to probe G- and F-actin content. KEY RESULTS:Basal expression and activity of PKC?2 and PKC? were increased in aortic VSMs of SHR, compared with those from WKY rats. Vasorelaxation of SHR aortas by propofol was markedly attenuated by LY333531 (a specific PKC? inhibitor) or the PKC? pseudo-substrate inhibitor. Furthermore, noradrenaline-enhanced phosphorylation, and the translocation of PKC?2 and PKC?, was inhibited by propofol, with decreased actin polymerization and PKC?2-mediated Ca2+ sensitization pathway in SHR aortas. CONCLUSION AND IMPLICATIONS:Propofol suppressed increased PKC?2 and PKC? activity, which was partly responsible for exaggerated vasodilation in SHR. This suppression results in inhibition of actin polymerization, as well as that of the PKC?2- but not PKC?-mediated, Ca2+ sensitization pathway. These data provide a novel explanation for the unwanted side effects of propofol.

SUBMITTER: Wang Y 

PROVIDER: S-EPMC5466522 | biostudies-literature | 2017 Jul

REPOSITORIES: biostudies-literature