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 peptide family thought to be important in appetite regulation. The present study compared the appetite-suppressant effect of subcutaneous urocortin in obese mice to its cardiovascular effects. Acutely, urocortin (100 nmol/kg iv) reduced blood pressure and increased heart rate in urethane anesthetized nonobese 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 the 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 administration, animals were pretreated for 3 days with urocortin (10 nmol/kg sc) or vehicle. Following urocortin pretreatment, urocortin-induced hypotension was similar to the effect in vehicle pretreated mice. However, urocortin-induced appetite suppression was reduced following 3 days of pretreatment with urocortin (10 nmol/kg sc) to ob/ob mice. These data suggest that the hypotensive and appetite-suppressant effects of urocortin are mediated by different mechanisms and tolerance to the hypotension did not readily occur in obese animals.
Cohen
M L
ML
Lilly Research Laboratories, Eli Lilly and Company, Lilly Corporate Center, Drop Code 0520, 46285, Indianapolis, IN, USA. cohenml@lilly.com
Bloomquist
W
W
Li
D
D
Iyengar
S
S
D000818:Animals; D001069:Appetite Regulation / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D003346:Corticotropin-Releasing Hormone / Q000008:administration & dosage / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D007279:Injections, Subcutaneous; D008297:Male; D051379:Mice; D008820:Mice, Obese / Q000502:physiology*; D023421:Models, Animal; D054832:Urocortins
D054832:Urocortins; D003346:Corticotropin-Releasing Hormone