Parasympathetic Cholinergic Vasodilator Mechanism in the Terminal Liver Microcirculation in Rats

Abstract

Changes in the diameter of liver sinusoids were studied by an intravital television microscope method in pentobarbital-anaesthetized rats. Dilatation of liver sinusoids was observed during parasympathetic neural stimulation and during acetylcholine administration. Frequency-dependent stimulation-effect relationships were obtained by electrical excitation of intact vagus nerves at supramaximal intensity fr-om 2 to 8 Hz. Acetylcholine concentration-effect relationships were also obtained by intraportal venous infusions of acetylcholine 30 pil for 5 s from 10-I to 10-2 mol I -1. Systemic cholinergic receptor blockade with atropine (1 mg kg 1) markedly reduced dilatation of liver sinusoids produced by both vagus nerve stimulation and acetylcholine administration. Changes in diameter of liver sinuLsoids with frequency of neural stimulation and with concentration of administered acetylcholine were also expressed as percentage of observed maximum effect and the respective stimulation-effect curves were constructed such that at a certain percentage of diameter change, the equivalent level of vagus nerve activity was represented by a given concentration of administered acetylcholine. Liver plasma concentration of acetylcholine presumably released during electrical vagal stimulation and reaching liver sinusoids was also estimated and found to be within physiological range. It is therefore proposed that rat liver sinusoids have the capacity for parasympathetic cholinergic vasodilatation.Evidence of an autonomic sympathetic control mechanism for the calibre of liver sinusoids in rats has been demonstrated recently Cheng, 1976, 1977]. Such an adrenergic mechanism is present in many other vascular beds such as brain, stomach, kidney, heart and skeletal muscle. In coronary and cerebral circulations of dogs, there also exists a parasympathetic mechanism which has the opposite effects of sympathetic mechanism on blood flow regulation [Feigl, 1969; D'Alecy and Rose, 1977]. A similar parasympathetic mechanism could be present in the liver too. Indeed, hepatic nerves receive fibers from coeliac plexus as well as both vagus nerves [Mikhail and Saleh, 1961;Sutherland, 1964], but the role of these parasympathetic fibres in liver sinusoids is little stLidied. In the present investigation direct electrical stimulation of vagus nerves and intraportal venous infusion of the parasympathetic neurotransmitter acetyleholine were used to test for the existence of a cholinergic vasodilator mechanism in rat liver sinusoids.Also, diffiCulty exists in interpreting relationships of physiological effects of administered cholinergic substances and effects produced by neural activity, i.e., 149

Electroacupuncture therapy in inflammation regulation: current perspectives

“…While increasing numbers of publications have reported on the role of vagal activity in hepatic hypertension and inflammation based on the concept of cholinergic anti-inflammatory reflex, 17 , 26 , 27 hepatic target cells of vagal efferent fibers have not been identified. 28 , 29 Similarly, autonomic connections to the spleen are unclear and controversial. In this regard, it is worthwhile to note one recent report showing that the electrophysiological and histological identification of serotonin-secreting enterochromaffin cells in the intestine that modulate synaptically connected afferent nerve fibers can fulfill the minimal requirement of brain–gut communication.…”

Anatomy of efferent hepatic nerves

“…Such neural influence may occur directly by stimulation of cells comprising the vascular wall or hepatic parenchymal cells. It may also occur indirectly by affecting the release of metabolites from parenchymal cells or mediators from nonparenchymal sinusoidal lining cells, which in turn influence surrounding structures or cells as suggested by reports of a neural influence on hepatic cellular metabolism (Shimazu, 1981, 1983, 1996; Lautt, 1983; Anil and Forbes, 1987; Jungermann, 1987; Lautt and Greenway, 1987; Friedman, 1988; Niijima, 1989; Gardemann et al, 1992; Püschel and Jungermann, 1994; Jungermann and Stümpel, 1999), hemodynamics (Hanson, 1978; Richardson, 1981; Richardson and Withrington, 1981, 1982; Lautt, 1983; Jungermann, 1987; Lautt and Greenway, 1987; Gardemann et al, 1992; Shimazu, 1996; Kurosawa et al, 2002), and the hepatic microvasculature (McCuskey, 1966, 1967; Koo et al, 1977; Koo and Liang, 1979a, 1979b, 1979c; Reilly et al, 1981, 1982; Koo, 1987; Shimazu, 1996; Wheatley and Almond, 1997).…”

High-frequency vagus nerve stimulation improves portal hypertension in cirrhotic rats

“…Early work by Koo and Liang2 3 showed that electrical vagus nerve stimulation and administration of ACh led to dilation of normal liver sinusoids in a frequency- and concentration-dependent manner, respectively. Since then, the existence of a cholinergic vascular neuroeffector system involving muscarinic receptor type 3 and endothelial nitric oxide synthase that reduces intrahepatic vascular resistance is generally accepted.…”