Effect of acute and subchronic subcutaneous urocortin on blood pressure and food consumption in ob/ob mice

Corticotropin-releasing factor and urocortin belong to a hypothalamic pepti de family thought to be important in appetite regulation. The present study compared the appetite-suppressant effect of subcutaneous urocortin in obes e mice to its cardiovascular effects. Acutely, urocortin (100 nmol/kg iv) r educed blood pressure and increased heart rate in urethane anesthetized non obese mice; effects similar to those produced by subcutaneous urocortin (10 and 100 nmol/kg sc) in nonobese and ob/ob mice. Over this same dose range (10-100 nmol/kg sc), urocortin dramatically inhibited food consumption in t he ob/ob mouse. To determine if the acute hypotensive effect of urocortin ( 10 nmol/kg sc) in the ob/ob mouse persisted after repeated urocortin admini stration, animals were pretreated for 3 days with urocortin (10 nmol/kg sc) or vehicle. Following urocortin pretreatment. urocortin-induced hypotensio n was similar to the effect in vehicle pretreated mice. However, urocortin- induced appetite suppression was reduced following 3 days of pretreatment w ith urocortin (10 nmol/kg sc) to ob/ob mice. These data suggest that the hy potensive and appetite-suppressant effects of urocortin are mediated by dif ferent mechanisms and tolerance to the hypotension did not readily occur in obese animals. (C) 2001 Elsevier Science Inc. All rights reserved.