Abstract
BACKGROUND: Mechanisms underlying abnormalities of circulation and renal function in cirrhosis are not completely understood. Our previous study revealed that primary afferent denervation by neonatal capsaicin treatment prevented the development of hyperdynamic circulation in portal hypertensive and cirrhotic rats. AIMS: The present study aimed to clarify the role of capsaicin sensitive nerves in the development of renal dysfunction and ascites formation in cirrhosis. METHODS: Rat pups were injected with capsaicin (50 mg/kg) or vehicle and allowed to grow. When they reached adulthood, cirrhosis was induced by bile duct ligation while controls received sham operation. Cardiac output and regional blood flows were measured by radioactive microspheres, glomerular filtration rate by (3)H inulin clearance, and urine volume, sodium excretion, and ascites formation were determined. Immunohistochemical staining for Fos in the brain stem cardiovascular regulatory nuclei, the nucleus of the solitary tract, and ventrolateral medulla was measured as an index of central neuronal activation. RESULTS: Increased cardiac output and renal blood flow, and decreased systemic vascular resistance, arterial pressure, renal vascular resistance, and glomerular filtration rate, as well as ascites, were found in vehicle treated cirrhotic rats. Neonatal capsaicin treatment completely blocked the development of hyperdynamic circulation and ascites, and improved renal function in cirrhotic rats. This was associated with complete abrogation of brain stem neuronal activation in capsaicin treated cirrhotic rats. CONCLUSIONS: These results indicate that intact primary afferent innervation is necessary for the development of not only the hyperdynamic circulation but also the renal dysfunction and ascites formation characteristic of cirrhosis.