vasoactive-intestinal-peptide and Hypertension--Portal

The liver is innervated by the vagus nerve. Its efferent neurotransmitters acetylcholine (ACh) and vasoactive intestinal peptide (VIP) are both well-known vasodilators. A study was undertaken to determine whether electrical vagus nerve stimulation (STIM) influences portal vein pressure.. The left vagus nerve upstream of the hepatic branch was stimulated at 5 Hz (ACh release) and 10 Hz (VIP release) in normal and cirrhotic rats.. STIM at both frequencies decreased portal pressure in normal rats while, in cirrhotic rats, only 10 Hz STIM resulted in long-lasting reduction of portal pressure. Hepatic branch vagotomy prevented the STIM-induced decrease in pressure, proving that the effect is a direct hepatic effect. Deafferentation of the left vagus nerve by pretreatment with capsaicin did not change the effect of STIM, showing that the vagus efferents and not the afferents are responsible for the decrease in portal pressure. Injecting microspheres before and after STIM showed that STIM did not lead to redistribution of systemic blood flow but decreased portal pressure by lowering intrahepatic resistance. Using in situ liver perfusion to evaluate the intrahepatic effect of ACh and VIP, both neurotransmitters significantly decreased the perfusion pressure in normal rats. VIP also decreased portal pressure in cirrhotic rats, confirming the results of STIM. This VIP-induced decrease in pressure could be prevented by a VIP receptor 2 antagonist. L-NAME did not inhibit the VIP effect in cirrhotic rats, indicating that VIP does not act via nitric oxide.. High-frequency electrical vagus stimulation improves portal hypertension in cirrhotic rats, most likely through release of VIP, binding to VIP receptor 2. As the technology is already in use for other applications, vagus nerve stimulation might be an important new strategy in the treatment of portal hypertension.

Topics: Acetylcholine; Animals; Cells, Cultured; Dose-Response Relationship, Drug; Hypertension, Portal; Liver Circulation; Liver Cirrhosis, Experimental; Male; Microcirculation; Microspheres; Portal Pressure; Rats; Rats, Wistar; Receptors, Vasoactive Intestinal Peptide, Type II; Regional Blood Flow; Signal Transduction; Vagus Nerve; Vagus Nerve Stimulation; Vasoactive Intestinal Peptide; Vasodilator Agents

Glucagon has been proposed as the mediator of splanchnic hyperemia in portal hypertension. Employing an assay specific for pancreatic glucagon, we reevaluated the relationship between this peptide and portal hypertension in the portal vein (PV)-stenosed rat model addressing, in particular, the effects of anesthesia and surgical stress. Plasma glucagon levels were similar in sham-operated and portal hypertensive rats: glucagon, sham vs PV stenosed: 110.7 +/- 17.1 pmol/liter vs 140.6 +/- 23.3 pmol/liter (NS). Furthermore, plasma levels of glucagon and the related peptide VIP were not significantly influenced by anesthesia or surgical stress, and levels remained similar under all conditions in sham-operated and PV-stenosed animals. We conclude that pancreatic glucagon is not elevated in the PV-stenosed rat; differences between these results and those describing hyperglucagonemia in this model cannot be explained on the basis of a differential response to stress but may reflect differences in glucagon assay system.

Topics: Anesthesia; Animals; Blood Glucose; Blood Pressure; Glucagon; Heart Rate; Hypertension, Portal; Insulin; Rats; Rats, Sprague-Dawley; Stress, Physiological; Surgical Procedures, Operative; Vasoactive Intestinal Peptide

To test the hypothesis that intestinal motility is delayed after hepatectomy, which alters the ecology of the enteric microflora and contributes to the development of bacterial translocation from the gut.. Open experimental study.. University department of surgery.. Adult male Sprague-Dawley rats (n = 6 in each group at each time point).. Sham operation, 90% hepatectomy, and portal venous obstruction.. Intestinal morphology, immunocytochemistry of the enteric nervous system, enteric bacterial growth in the small intestine and colon, and intestinal transit time.. Intestinal transit was already delayed one hour after 90% hepatectomy, and histopathological alterations and overgrowth by Escherichia Coli had developed after two hours. There were significant differences in intestinal transit time between sham operated rats and those subjected to portal venous obstruction on the one hand, and those that underwent 90% hepatectomy on the other. There was no difference in intestinal transit time between rats with portal venous obstruction and the sham operated animals.. Delayed intestinal transit after 90% hepatectomy may contribute to enteric bacterial overgrowth and thereby contribute to the development of bacterial translocation from the gut.

Topics: Animals; Cecum; Chromium Radioisotopes; Colon; Duodenum; Enteric Nervous System; Enterobacteriaceae; Escherichia coli; Gastrointestinal Motility; Hepatectomy; Hypertension, Portal; Ileum; Jejunum; Male; Neuropeptide Y; Portal Vein; Rats; Rats, Sprague-Dawley; Substance P; Vasoactive Intestinal Peptide

It is well known that portal hypertension is associated with a hyperdynamic systemic circulatory state. This study measures systemic and splanchnic haemodynamics in an experimental rat model of hepatic cirrhosis. It also investigates the association between haemodynamic changes in cirrhotic animals and circulating levels of the vasoactive hormones glucagon and vasoactive intestinal polypeptide (VIP). Splanchnic blood flow was significantly increased in the cirrhotic group (13.2 +/- 1.3 vs. 9.2 +/- 1.6 ml/min, P < 0.05). Circulating levels of glucagon and VIP were two and five fold increased respectively in cirrhotic animals compared to controls. There was a strong correlation between portal pressure and glucagon levels in the cirrhotic group (r = 0.85). Raised splanchnic blood flow is partly responsible for elevated portal pressure in this model and this rise may be humorally mediated.

Topics: Animals; Cardiac Output; Glucagon; Hemodynamics; Hypertension, Portal; Liver Cirrhosis, Experimental; Male; Portal Pressure; Rats; Rats, Sprague-Dawley; Splanchnic Circulation; Vascular Resistance; Vasoactive Intestinal Peptide; Vasodilation

Topics: Adult; Female; Histamine; Humans; Hypertension, Portal; Liver Cirrhosis; Male; Middle Aged; Portal Vein; Serotonin; Somatostatin; Vasoactive Intestinal Peptide