NEONATAL CAPSAICIN TREATMENT DOES NOT PREVENT SPLANCHNIC VASODILATATION IN PORTAL-HYPERTENSIVE RATS

It has been suggested that the peripheral sensory neurons are involved in the splanchnic hemodynamic changes of portal hypertension. Therefo re the influence of permanent ablation of sensory neurons by neonatal capsaicin pretreatment (50 mg/kg, subcutaneously) on the development o f the hyperdynamic splanchnic circulation in portal-hypertensive rats was studied. In adulthood, portal hypertension was induced with partia l portal vein ligation. In study 1, systemic and splanchnic hemodynami cs were measured by means of a radiolabeled-microsphere technique in p ortal-hypertensive rats, under ketamine anesthesia, pretreated with ca psaicin or vehicle. Mean arterial pressure, heart rate, cardiac index, systemic and splanchnic vascular resistance, portal pressure, portal venous inflow, portal-collateral resistance and portal-systemic shunti ng were not significantly different between capsaicin-pretreated and v ehicle-pretreated rats. In study 2, gastric mucosal blood flow, measur ed by means of hydrogen gas clearance, and the hemoglobin and oxygen c ontent of the gastric mucosa, as assessed with reflectance spectrophot ometry, were not significantly different in the two groups of anesthet ized portal-hypertensive rats pretreated with capsaicin or vehicle. In study 3, we confirmed the effectiveness of neonatal capsaicin pretrea tment by measuring calcitonin gene-related peptide content of the gast ric corpus wall. Capsaicin pretreatment caused a depletion of calciton in gene-related peptide by at least 98% compared with that in vehicle- pretreated rats. These results do not support a role of capsaicin-sens itive sensory neurons that innervate the gastrointestinal tract in the development of the splanchnic vasodilatation characteristically obser ved in chronic portal hypertension.