Propofol-induced relaxation of rat aorta is altered by aging

Shibata, Yoko; Kawahito, Shinji; Takaishi, Kazumi; Mita, Naoji; Kinoshita, Hiroyuki; Hatakeyama, Noboru; Azma, Toshiharu; Nakaya, Yutaka; Kitahata, Hiroshi

doi:10.2152/jmi.61.278

Cited by 6 publications

(3 citation statements)

References 36 publications

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“…Moreover, other members of the TRP family, in particular TRPV4 and TRPM8 channels, which are important for the regulation of blood vessel tone, need to be more fully characterized in this context ( Melanaphy et al, 2016 ; Dryn et al, 2018 ). There is accumulating evidence that some anaesthetics can affect these two types of channels ( Abeele et al, 2013 ; Wang et al, 2019 ), as well as vascular tone ( Liu et al, 2009 ; Gille et al, 2012 ; Sakai et al, 2014 ), therefore this research area is also relevant and promising.…”

Section: Conclusion and Further Researchmentioning

confidence: 99%

General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain

2023

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General anesthesia produces multiple side effects. Notably, it temporarily impairs gastrointestinal motility following surgery and causes the so-called postoperative ileus (POI), a multifactorial and complex condition that develops secondary to neuromuscular failure and mainly affects the small intestine. There are currently limited medication options for POI, reflecting a lack of comprehensive understanding of the mechanisms involved in this complex condition. Notably, although acetylcholine is one of the major neurotransmitters initiating excitation-contraction coupling in the gut, cholinergic stimulation by prokinetic drugs is not very efficient in case of POI. Acetylcholine when released from excitatory motoneurones of the enteric nervous system binds to and activates M2 and M3 types of muscarinic receptors in smooth muscle myocytes. Downstream of these G protein-coupled receptors, muscarinic cation TRPC4 channels act as the major focal point of receptor-mediated signal integration, causing membrane depolarisation accompanied by action potential discharge and calcium influx via L-type Ca2+ channels for myocyte contraction. We have recently found that both inhalation (isoflurane) and intravenous (ketamine) anesthetics significantly inhibit this muscarinic cation current (termed mICAT) in ileal myocytes, even when G proteins are activated directly by intracellular GTPγS, i.e., bypassing muscarinic receptors. Here we aim to summarize Transient Receptor Potential channels and calcium signalling-related aspects of the cholinergic mechanisms in the gut and visceral pain, discuss exactly how these may be negatively impacted by general anaesthetics, while proposing the receptor-operated TRPC4 channel as a novel molecular target for the treatment of POI.

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Section: Conclusion and Further Researchmentioning

confidence: 99%

General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain

2023

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“…However, propofol has an obvious side effect of inducing hypotension, particularly in patients with high blood pressure or in elderly patients. Furthermore, patients with vena cava collapse are prone to develop significant hypotension when treated with propofol, which may be a direct result of vascular relaxation ( 1 – 4 ). Certain studies have indicated that propofol elicits vascular relaxation via the following mechanisms: i) Activation of large-conductance calcium voltage-activated potassium channels (BK Ca ) ( 2 ); ii) activation of ATP-sensitive K + channels (K ATP ) ( 5 ); iii) inhibition of voltage-operated calcium channels and receptor-operated calcium channels ( 6 ); and iv) increases in the availability of nitric oxide ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Propofol‑induced vasodilation of mesenteric arterioles via BKCa channel and gap junction

Wan

Wang

et al. 2018

Exp Ther Med

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The present study aimed to investigate the role of propofol in mediating the vasomotor activity of the mesenteric arteriole (MA) of Sprague Dawley (SD) rats, and to elucidate the underlying mechanisms. The pressure myograph technique was used to examine the effect of different concentrations of propofol on the relaxation of blood vessels in the 2–3 mm MA segments freshly separated from the SD rats. The whole-cell patch-clamp technique was applied to observe the outward current of single vascular smooth muscle cells (VSMCs) obtained from the MAs of the SD rats. Furthermore, immunofluorescence was utilized to assess the expression of connexin (Cx) in the MAs of SD rats. The results indicated the following: i) Propofol relaxed the MA of SD rats in a concentration-dependent manner from 1×10−7 to 3×10−4 mol/l; ii) in the acutely dissociated VSMCs, propofol (1×10−7 to 3×10−4 mol/l) enhanced the outward current of VSMCs in a concentration-dependent manner; iii) the enhanced outward currents induced by propofol (1×10−5 mol/l) may be reversed by tetraethylammonium (TEA; 1 mmol/l), a calcium-activated K+ channel inhibitor; iv) the effect of propofol on the relaxation of the vasculature wAS reduced after perfusion with 1 mmol/l TEA; v) Cx40, Cx43 and Cx45 were expressed on the MA; 6) 18β-glycyrrhetintic acid and 2-aminoethoxydiphenyl borate, two types of gap junction blocker, inhibited the propofol-induced relaxation. The present study provides evidence that propofol relaxes the MA, which may be associated with its effect of enhancing the channel current of large-conductance calcium voltage-activated potassium channels, contributing to the K+ outflow and leading to VSMC hyperpolarization; the gap junction may facilitate the hyperpolarization, which may lead to vascular synchronized relaxation and thereby reduce the blood pressure.

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“…Propofol (2,6-di-isopropylphenol) become a widely used intravenous anesthetic because of its rapid onset, short duration of action, and rapid elimination. It triggers vasorelaxation of a number of systemic vascular beds, including the aortae [ 1 ], the coronary arteries [ 2 ], the renal arteries [ 3 ]. However, effects of propofol on the pulmonary vascular system remain unclear.…”

Section: Introductionmentioning

confidence: 99%

The bifunctional effect of propofol on thromboxane agonist (U46619)-induced vasoconstriction in isolated human pulmonary artery

Hao

Wang

Kuang

et al. 2017

Korean J Physiol Pharmacol

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Propofol is known to cause vasorelaxation of several systemic vascular beds. However, its effect on the pulmonary vasculature remains controversial. In the present study, we investigated the effects of propofol on human pulmonary arteries obtained from patients who had undergone surgery. Arterial rings were mounted in a Multi-Myograph system for measurement of isometric forces. U46619 was used to induce sustained contraction of the intrapulmonary arteries, and propofol was then applied (in increments from 10–300 µM). Arteries denuded of endothelium, preincubated or not with indomethacin, were used to investigate the effects of propofol on isolated arteries. Propofol exhibited a bifunctional effect on isolated human pulmonary arteries contracted by U46619, evoking constriction at low concentrations (10–100 µM) followed by secondary relaxation (at 100–300 µM). The extent of constriction induced by propofol was higher in an endothelium-denuded group than in an endothelium-intact group. Preincubation with indomethacin abolished constriction and potentiated relaxation. The maximal relaxation was greater in the endothelium-intact than the endothelium-denuded group. Propofol also suppressed CaCl2-induced constriction in the 60 mM K+-containing Ca2+-free solution in a dose-dependent manner. Fluorescent imaging of Ca2+ using fluo-4 showed that a 10 min incubation with propofol (10–300 µM) inhibited the Ca2+ influx into human pulmonary arterial smooth muscle cells induced by a 60 mM K+-containing Ca2+-free solution. In conclusion, propofol-induced arterial constriction appears to involve prostaglandin production by cyclooxygenase in pulmonary artery smooth muscle cells and the relaxation depends in part on endothelial function, principally on the inhibition of calcium influx through L-type voltage-operated calcium channels.

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Propofol-induced relaxation of rat aorta is altered by aging

Cited by 6 publications

References 36 publications

General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain

General anaesthesia-related complications of gut motility with a focus on cholinergic mechanisms, TRP channels and visceral pain

Propofol‑induced vasodilation of mesenteric arterioles via BKCa channel and gap junction

The bifunctional effect of propofol on thromboxane agonist (U46619)-induced vasoconstriction in isolated human pulmonary artery

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