Korean J Physiol Pharmacol.  2014 Oct;18(5):377-381. 10.4196/kjpp.2014.18.5.377.

The Relaxant Effect of Propofol on Isolated Rat Intrapulmonary Arteries

• Zhang G
• Cui J
• Chen Y
• Ma J

• KMID: 2285535
• DOI: http://doi.org/10.4196/kjpp.2014.18.5.377

Abstract

Propofol is a widely used anesthetic. Many studies have shown that propofol has direct effects on blood vessels, but the precise mechanism is not fully understood. Secondary intrapulmonary artery rings from male rats were prepared and mounted in a Multi Myograph System. The following constrictors were used to induce contractions in isolated artery rings: high K+ solution (60 mmol/L); U46619 solution (100 nmol/L); 5-hydroxytryptamine (5-HT; 3 micromol/L); or phenylephrine (Phe; 1 micromol/L). The relaxation effects of propofol were tested on high K+ or U46619 precontracted rings. Propofol also was added to induce relaxation of rings preconstricted by U46619 after pretreatment with the nitric oxide synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME). The effects of propofol on Ca2+ influx via the L-type Ca2+ channels were evaluated by examining contraction-dependent responses to CaCl2 in the absence or presence of propofol (10 to 300 micromol/L). High K+ solution and U46619 induced remarkable contractions of the rings, whereas contractions induced by 5-HT and Phe were weak. Propofol induced dose-dependent relaxation of artery rings precontracted by the high K+ solution. Propofol also induced relaxation of rings precontracted by U46619 in an endothelium-independent way. Propofol at different concentrations significantly inhibited the Ca2+-induced contractions of pulmonary rings exposed to high K+-containing and Ca2+-free solution in a dose-dependent manner. Propofol relaxed vessels precontracted by the high K+ solution and U46619 in an endothelium-independent way. The mechanism for this effect may involve inhibition of calcium influx through voltage-operated calcium channels (VOCCs) and receptor-operated calcium channels (ROCCs).

Keyword

Calcium influx; Endothelium; Propofol; Pulmonary artery

MeSH Terms

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Animals
Arteries*
Blood Vessels
Calcium
Calcium Channels
Endothelium
Humans
Male
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Phenylephrine
Propofol*
Pulmonary Artery
Rats*
Relaxation
Serotonin
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Calcium
Calcium Channels
NG-Nitroarginine Methyl Ester
Nitric Oxide Synthase
Phenylephrine
Propofol
Serotonin

Figure

• 

  Fig. 1 Effect of propofol on 60 mmol K+ preconstrictedsecondary intrapulmonary artery rings. Responses are expressed as percentage of precontraction induced by 60 mmol/L K+-containing solution. Propofol induced relaxation in rings contracted by 60 mmol/L K+-containing solution in a concentration-dependent manner (x±s, n=6).

• 

  Fig. 2 Effect of propofol on 100 nmol/L U46619 preconstricted-secondary intrapulmonary artery rings. Responses are expressed as percentage of precontraction induced by 100 nmol/L U46619. Propofol induced relaxation in rings contracted by 100 nmol/L U46619 in a concentration-dependent manner (x±s, n=6).

• 

  Fig. 3 The role of the endothelium on the vasodilation effect of propofolusing endothelium intact rings preconsricted by 100 mmol/L U46619. Responses are expressed as percentage of precontraction induced by 100 nmol/L U46619. Propofol indued relaxation in the absence or presence of L-NAME (the nitric oxide synthase inhibitor). No significant difference of Emax was observed in the absence or presence of L-NAME (n=5 for each group).

• 

  Fig. 4 The role of the endothelium on the vasodilation effect of propofolusing endothelium intact rings or endothelium denuded rings preconsricted by 100 mmol/L U46619. Responses are expressed as percentage of precontraction induced by 100 nmol/L U46619. No significant difference in Emaxwas observed between the endothelium-intact and endothelium-denuded groups (n=5 for each group).

• 

  Fig. 5 CaCl2-induced contraction in Ca2+-free solution containing 60 mmol/L K+ in the absence (n=5) and presence of propofol (10 to 300 µmol/L, n=5). A significant difference in Emax between control and propofol-treated groups is indicated by an asterisk (p<0.001).

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