Reactivity of human omental blood vessels. Effects of 5-hydroxytryptamine, substance P and the intravenous anaesthetic propofol

Abstract: Regulation of blood flow involves several endogenous substances and mechanisms, and exogenous substances may also affect the blood flow. In the present thesis, human omental blood vessels were investigated in vitro concerning (i) characteristics of 5-hydroxytryptamine (5-HT) receptors; (ii) mediators of substance P (SP)-induced relaxation; (iii) direct and indirect (via effects on sympathetic neurotransmission) effects of the intravenous anaesthetic propofol. In human omental arteries, contractile 5-HT1 and 5-HT2 receptors were demonstrated. No evidence for contractile 5-HT3 or 5-HT4 and relaxing 5-HT1, 5-HT2, 5-HT3 or 5-HT4 receptors was found. In human omental arteries and veins, SP-induced relaxation seems to be mediated via nitric oxide (NO) and endothelium-dependent hyperpolarization, possibly due to activation of high conductance Ca2+-sensitive K+-channel (BKCa). Direct effects of propofol in human omental arteries and veins include relaxation of vascular smooth muscle mediated via endothelium-independent hyperpolarization and attenuation of the response to contractile agents. The hyperpolarization is possibly due to propofol-induced activation of BKCa. The propofol-induced attenuation of the response to contractile agents may be explained by a decreased release of intracellularly stored calcium rather than a decreased influx of calcium from the extracellular space. Propofol at clinical concentrations seems to enhance sympathetic neurotransmission in human omental arteries, but not veins. This may be due to an increased availability of noradrenaline (NA) in the neuromuscular junction, resulting from a reduced presynaptic reuptake. Propofol at probably supraclinical concentrations, on the other hand, seems to impair the sympathetic neurotransmission in both human omental arteries and veins, possibly due to an inhibitory effect on the NA release from the sympathetic nerves.