Nucleus tractus solitarii lesions alter the metabolic and hyperthermic response to central prostaglandin E1 in the rat.

1. Given that the nucleus tractus solitarii (NTS) may regulate the ability of brown adipose tissue to evoke non-shivering thermogenesis and that brown fat may mediate the rise in whole-body metabolism observed following central pyrogen administration, we assessed whether interruption of baroreceptor afferents coursing though the NTS would interfere with the ability of prostaglandin E1 to evoke a normal fever response profile. 2. Infusion of 150-600 ng of prostaglandin E1 (PGE1) into a lateral cerebral ventricle of the conscious rat resulted in a rise in core temperature, and also an increase in whole-body metabolic rate, brown adipose tissue temperature, arterial blood pressure and heart rate. 3. Following bilateral electrolytic lesions to the NTS, resting core and brown fat temperatures, metabolic rates, blood pressures and heart rates in the NTS-lesioned animals were comparable to control rats. However, the PGE1-evoked increase in metabolic rate, along with the rise in core and brown adipose tissue temperatures and heart rate were attenuated. The pressor response was, however, enhanced, possibly due to the demonstrated interference by the lesions with normal baroreflex control. 4. The findings suggest that the nucleus tractus solitarii region of the rats' brain may be important in mediating the thermogenesis evoked by central PGE1.

Modulation of brown adipose tissue-mediated thermogenesis by lesions to the nucleus tractus solitarius in the rat.

Given that relatively little is known regarding the central control of brown adipose tissue (BAT)-mediated thermogenesis the present study assessed whether the direct pharmacological stimulation of beta- or alpha-adrenergic receptors located on the brown adipocytes would result in a typical thermogenic response following electrolytic lesions to the nucleus tractus solitarius (NTS). Bilateral electrolytic lesions to the NTS in the rat effectively disrupted the baroreceptor reflex arc. It was observed that the metabolic and temperature responses to either norepinephrine (1, 5, or 25 micrograms/kg/min) or to the beta-agonist isoproterenol (0.5 micrograms/kg/min) were significantly attenuated in the NTS-lesioned rats relative to the control animals with an intact baroreflex. Conversely, the cardiovascular effects of norepinephrine or of the alpha-agonist phenylephrine (10 micrograms/kg/min) were enhanced in the NTS-lesioned animals. The results suggest that the functional capacity of the brown adipocytes was reduced following NTS lesions and points to an alteration in the ability of beta-receptors to respond to pharmacological stimulation with a typical thermogenic response.

Contribution of brown adipose tissue to central PGE1-evoked hyperthermia in rats.

The relative contribution of several effector systems to a prostaglandin E1-(PGE1) evoked hyperthermia was examined. Infusion of 150 ng of PGE1 into a lateral cerebral ventricle increased core temperature and whole body metabolic rate, brown adipose tissue temperature, systolic blood pressure, and heart rate. Pretreating the animals with a nonselective beta-antagonist propranolol (1 mg/kg iv in 0.3 ml followed by 3 mg.kg-1.h-1 in 0.3 ml/h) not only attenuated the rise in metabolism observed after the central administration of 150 ng PGE1 but also diminished the elevation in both core and brown fat tissue temperatures as well as the increase in heart rate. Pretreating the animals with the alpha-antagonist prazosin (2 mg/kg im followed by 50 micrograms.kg-1.h-1 iv in 0.3 ml/h) somewhat reduced the rise in whole body metabolism, suppressed the elevation in core temperature, but failed to alter the rise in brown adipose tissue temperature normally seen after the central administration of PGE1. Moreover, both the rise in systolic blood pressure and heart rate were attenuated when the PGE1 administration was preceded by prazosin. These results suggest that brown adipose tissue is an important effector organ responsible for mediating the hyperthermic response observed after the intracerebral injection of PGE1. In addition, the results indicate that alterations in vasomotor tone may also be important in producing or sustaining the elevated core temperature found after a pyrogen administration.

The effectiveness of arginine vasopressin and sodium salicylate as antipyretics in the Brattleboro rat.

The infusion of either 30 micrograms/microliters (approx. 100 micrograms/kg/h) of sodium salicylate or 10 ng/microliters (10(-5) M) arginine vasopressin within the ventral septal area of the Brattleboro rat brain reduced a centrally induced prostaglandin E1 (PGE1) hyperthermia when compared with infusions of artificial cerebrospinal fluid. Conversely, the infusion of a related peptide, oxytocin (10 ng/microliters (10(-5) M), or 33 ng/kg/h) failed to alter the rise in core temperature following the PGE1 injection. These results suggest that the vasopressin receptors reported to be present in the Brattleboro rat may respond normally to exogenously administered vasopressin, thus allowing for the antipyretic action. Moreover, the antipyretic effects of sodium salicylate suggest that aspirin-like drugs may induce the release of alpha-melanocyte-stimulating hormone which, in turn, attenuates the PGE1-evoked fever. Given recent evidence, however, which suggests that the Brattleboro rat may contain vasopressin both peripherally and within the brain, the antipyretic action of sodium salicylate may be alternatively explained through the endogenous release of vasopressin.

Indomethacin-induced antipyresis in the rat: role of vasopressin receptors.

Infusion of 15 micrograms/microliters (approximately 120 micrograms/kg/h) of indomethacin within the ventral septal area of the rat brain significantly reduced a centrally induced prostaglandin E1 (PGE1) hyperthermia when compared with infusions of artificial cerebrospinal fluid. A bolus injection of a V1 receptor antagonist, d(CH2)5Try(Me)AVP, (200, 2000, or 20,000 pmol) within the ventral septal area had no effect of body temperature alone but did suppress the PGE1-induced fever. Similar bolus injections of the V1 receptor antagonist within the ventral septal area failed to alter the antipyretic action of indomethacin on the hyperthermia resulting from centrally administered PGE1. Central injections of a V2 receptor antagonist failed to alter either the PGE1-induced fever or the indomethacin-evoked antipyresis. The results suggest that the V1 receptor antagonist may exert non-specific neurodepressant effects which may interfere with the expression or production of PGE1 hyperthermia and may further mask any contribution of arginine vasopressin to the antipyretic effects of indomethacin.

Goldblatt hypertension and operant thermoregulation in shaved, sialoadenectomized rats.

The thermobehavioral consequences of angiotensinogenic two-kidney (2K) and sodium-volume dependent one-kidney (1K) forms of Goldblatt (one-clip) renovascular hypertension were assessed in shaved, sialoadenectomized rats. The 2K group (n = 8) underwent unilateral renal artery stenosis with the contralateral kidney left intact; whereas the Sham-Operation (Sham-Op) Control group (n = 7) received only a laparotomy. The 1K group (n = 8) underwent unilateral renal artery stenosis with contralateral nephrectomy, and the Uninephrectomy Control group (n = 6) was only unilaterally nephrectomized. Shaping and testing was conducted in a convective thermal controller that permitted the experimenters to control, through continuously reinforced bar-pressing, the ambient temperature during exposure to warm (37 degrees C) or cold (17 degrees C) temperatures. Testing at each temperature occurred over two 6-hr sessions with an interpolated 48-hr rest period. Both 2K and 1K hypertensive rats exhibited longer durations of heat escape than their appropriate normotensive controls across both testing sessions. No differences were detected in response frequency, duration of cold escape responding, or body temperature. The results suggest that either the increased vascular resistance or the neuroendocrine-sympathetic disorder linked to the pathogenesis of Goldblatt renovascular hypertension may promote heat retention or lower heat tolerance.