Propofol attenuates angiotensin II-induced vasoconstriction by inhibiting Ca2+-dependent and PKC-mediated Ca2+ sensitization mechanisms

Abstract

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.

Propofol induces excessive vasodilation of aortic rings by inhibiting protein kinase Cβ2 and θ in spontaneously hypertensive rats

“…The results from clinical studies and hypertensive animal models clearly demonstrate that the use of propofol for anaesthesia induction is often accompanied with profound hypotension and haemodynamic instability, and its safety in patients with hypertension has been debated for a long time. Although in blood vessel models, propofol has been demonstrated to influence cellular processes including calcium signalling (Lawton et al , ; Han et al , ), sympathetic neurotransmission (Ebert, ; Han et al , ) and the function of endothelium (Wang et al , ; Gragasin et al , ), propofol can also inhibit PKCs in VSMCs (Tanabe et al , ; Yu et al , ; Kuriyama et al , ). Although PKCs have emerged as new targets for treating genetic hypertension in various hypertensive models, the principal finding of the present study is that the enhanced expression and activation of two PKC isoforms, PKCβ2 and PKCθ, in SHR aortic smooth muscle are at least partly involved in the profound relaxation induced by propofol.…”

“…This hypotension may be due to its direct vasodilation (Gragasin et al , ), myocardial depression (Yang et al , ) and decrease in sympathetic activity (Ebert, ). At vascular smooth muscle (VSM) levels, the direct relaxant action of propofol on the vasculature has been suggested to be mediated through the PKC‐regulated, contractile Ca 2+ sensitization pathway (Kuriyama et al , ).…”

“…Although inhibition of Ca 2+ mobility by propofol has been demonstrated to contribute to the drug‐induced relaxation in VSM in hypertension (Kuriyama et al , ; Lawton et al , ), PKCs may have many effects on drug‐induced changes in vascular tension. Activation of PKCs in endothelium mediates thrombin and propofol‐enhanced NO bioavailability (Motley et al , ; Wang et al , ), whereas the activation of PKCs in VSM mediates agonist‐induced contraction (Kitazawa and Kitazawa, ; El‐Yazbi et al , ).…”

The Mechanism of NPC-14686-Induced [Ca^(2+)]i Rises and Non-Ca^(2+)-Triggered Cell Death in MG63 Human Osteosarcoma Cells

“…Inhibition of protein kinase C inhibited NPC-14686induced [Ca 2+ ] i rise. Protein kinase C is known to associate with Ca 2+ signaling in many cases (3,16). It seems that PLC-dependent pathways played a significant role in NPC-14686-induced Ca 2+ release, since the response was abolished by U73122.…”

Effects of propofol and sevoflurane on isolated human umbilical arteries pre‐contracted with dopamine, adrenaline and noradrenaline

“…34,35 The plasma concentration of propofol in patients during the induction and maintenance of general anesthesia is estimated at 2-5 μg/mL which corresponds to approximately 10 −6 -10 −4 M. 36 Propofol concentration used in the present study is within the limits of the clinical range. 37 Likewise, sevoflurane was administrated to the organ bath in 1.2% (0.5 MAC), 2.4% (1 MAC) and 3.6% (2 MAC) concentrations which are used for induction and maintenance of anesthesia.…”