Effect of propranolol on endotoxin-induced pyrogenesis in newborn and adult guinea pigs

Abstract

Previous studied have shown that nonshivering thermogenesis (NST) is the prevailing mechanism of fever production in both newborn (during the first 2–3 wk of life) and adult cold-acclimated guinea pigs. This study was undertaken to determine whether this process may be mediated by noradrenergic sympathetics. The temperatures in the interscapular brown fat pad (Tbat) and the colon (Tre), the rate of oxygen consumption (VO2), and shivering activity were measured continuously for 5 h at 27 degrees C ambient temperature in 8- and 16-day-old and adult cold-acclimated guinea pigs following 2 mug/kg iv of Salmonella enteritidis endotoxin, with and without 6.0 mg/kg of propranolol (a beta-adrenergic blocker) injected ip 2 min before the endotoxin. In the older animals, the increase in Tbat normally produced by endotoxin was reduced by propranolol administration, but shivering set in, maintaining both VO2 and Tre at their febrile levels. In the newborn animals, Tbat also was decreased by propranolol, but shivering did not set in, so that VO2 and Tre fell below their febrile values. It is concluded that endotoxin-induced NST is controlled by noradrenergic sympathetics. The failure of NST to be replaced in the present newborn guinea pigs by visible shivering might be related to other observations that the onset of shivering at this age occurs only when Tre is significantly reduced.