Capsaicin treatment blocks development of hyperkinetic circulation in portal hypertensive and cirrhotic rats

Abstract

To investigate a possible role of primary afferent innervation in the pathogenesis of hyperkinetic circulation in cirrhosis or portal hypertension, we used capsaicin to denervate the primary afferent nerves. Rat pups were injected with capsaicin (50 mg/kg) or a vehicle and were allowed to grow. When they reached young adulthood, operations to induce portal hypertension by portal vein stenosis or cirrhosis by bile duct ligation were performed. A control group had sham operation. Cardiac output and regional blood flows were measured in unrestrained conscious rats by radioactive microspheres. Capsaicin-treated portal hypertensive and cirrhotic rats had cardiac output and systemic vascular resistance similar to sham-operated rats, whereas the vehicle-treated portal hypertensive and cirrhotic rats showed the hyperkinetic circulation. No hemodynamic effect of capsaicin on sham-operated rats was detected. Capsaicin-treated rats did not demonstrate a splanchnic or renal hyperemia, but the percentage of cardiac output in these vascular beds was similar to controls. These results suggest that capsaicin treatment blocked the generalized vasodilatation in cirrhotic and portal hypertensive rats. Arterial pressure and heart rate were not modified in any group. These results show that denervation of capsaicin-sensitive primary afferent nerves in cirrhotic and portal hypertensive rats blocked the expected development of hyperkinetic circulation. We conclude that primary afferent innervation may be important in the genesis of hyperdynamic circulation in portal hypertension and cirrhosis.