Cold defense mechanisms in vagotomized rats.

Abstract

Subdiaphragmatically vagotomized rats cannot mount a febrile response to pyrogens and are believed to have severe thermoregulatory deficiencies. We addressed the issue of thermoeffector competence of vagotomized rats by asking three questions. In Expt. 1 we asked, can vagotomized rats readily recruit tail skin vasoconstriction in the course of a moderate cold exposure? In Expt. 2 the question was, can brown adipose tissue (BAT) thermogenesis readily be activated in vagotomized rats (e.g., in response to a tail pinch)? In Expt. 3, we investigated the question: can vagotomized rats elevate their body temperature in response to ephedrine (a drug of high hyperthermizing potential) to the same extent as sham-operated controls? Rats were vagotomized or sham operated and implanted with a catheter into the jugular vein and a thermocouple into the interscapular BAT. To prevent the common complications of vagotomy, special perioperative care was given. During experiments, colonic, tail skin, and BAT temperatures (Tc, Tsk, and TBAT, respectively) were measured. The vagotomized animals were well nourished and had a body mass (325 +/- 6 g) similar to that of the controls (338 +/- 6 g). In Expt. 1, in response to external cooling (15 degrees C, 1 h), the vagotomized (n = 30) and sham-operated (n = 31) rats recruited tail skin vasoconstriction at close values of both Tc (37.84 +/- 0.08 and 37.97 +/- 0.07 degrees C) and Tsk (33.16 +/- 0.17 and 33.18 +/- 0.18 degrees C, respectively). In Expt. 2, tail pinch-associated stress in vagotomized rats resulted in a sharp rise in the TBAT-Tc gradient by 0.3-1.0 degree C. In Expt. 3, ephedrine administered intravenously (whether in a 5 or 35 mg/kg dose) evoked similar hyperthermic responses in the vagotomized and sham-operated rats: a moderate (approximately 2.5 degrees C) Tc rise in the low dose and a "supramaximal" (approximately 5.0 degrees C) rise in the high dose. In sum, the answer to all three questions asked is yes. Vagotomized rats, at least when well nourished, exhibit no signs of thermoeffector deficiency. It is, therefore, not effector incompetence but rather vagal deafferentation per se that can explain the febrile irresponsiveness of vagotomized rats.