Comparison of the effects of high ambient temperature and clonidine on autonomic functions in man

The effects of two interventions, high ambient temperature, a sympathetic activator, and clonidine, a centrally acting sympatholytic drug, were compared on a number of autonomic functions. Eight healthy male volunteers participated in four weekly sessions. Each session was associated with one of the following treatments: placebo (physiological saline infused intravenously over 10 min) at 20°C; clonidine hydrochloride (1.5 μg kg^-1 in 10 ml infused intravenously over 10 min) at 20°C; placebo at 40°C; clonidine at 40°C. Subjects were allocated to treatments and sessions according to a double-blind (for drug condition) balanced design. In each session, the following indices of autonomic function were recorded: systolic and diastolic blood pressure, heart rate, salivation, body temperature, plasma noradrenaline and adrenaline concentrations, baseline and carbachol-evoked sweating, physiological finger tremor. Raised ambient temperature (40°C) caused increases in heart rate, body temperature, carbachol-evoked sweating and physiological finger tremor. Clonidine (at 20°C) reduced systolic blood pressure, body temperature, salivation and plasma noradrenaline concentration, but did not affect any of the other measures. Clonidine (at 40°C) counteracted the increase in heart rate, but not the increases in carbachol-evoked sweating and finger tremor, evoked by high ambient temperature. The high ambient temperature condition abolished the body-temperature-lowering effect of clonidine, but did not modify the effects of clonidine on systolic blood pressure, salivation and plasma noradrenaline concentration. These results indicate that while the effects of the heat stressor are consistent with an increase in sympathetic activity, and most of the effects of clonidine are consistent with a decrease in sympathetic activity, only two functions (body temperature and heart rate) were affected in opposite directions by the two interventions. Indeed, physiological antagonism between the two interventions could be demonstrated on body temperature and heart rate only, and there was no evidence for an interaction between the effects of the two variables on any of the other indices of autonomic activity. The failure of clonidine to affect two sympathetically mediated functions, carbachol-evoked sweating and physiological finger tremor, under either temperature condition, indicates that central α₂-adrenoceptors cannot be involved in the regulation of these functions. Received: 28 June 1996 / Accepted: 22 November 1996     

Effects of prazosin on metabolism and body temperature in normothermic rabbits

An attempt was made to study the influence of prazosin on thermoregulatory parameters. Two sets of experiments were carried out in rabbits. In the first set of experiments prazosin was given as 3 h infusion intravenously, (iv) (0.1, 0.25 and 0.5 mg/kg/h) or intracerebroventricularly, (icv) (20, 50 and 100 micrograms/animal) at an ambient temperature of 22 degrees C. Iv infusion caused a fall while icv administration a rise in body temperature. In the second set of experiments at different ambient temperatures (Ta = 4, 22, 28 degrees C) the following thermoregulatory parameters were recorded: rectal (Tre) and ear skin (Te) temperatures, metabolic rate (M), respiratory heat loss (Eres). The most evident result of iv infusion of prazosin in a dose of 0.25 mg/kg/h was a fall in Tre accompanied by a decrease in metabolic rate at ambient temperature of 4 degrees C. At Ta of 22 degrees C and 28 degrees C prazosin iv (0.25 mg/kg/h) induced only minimal changes in measured parameters. The results of the experiments may suggest that prazosin given peripherally induced hypothermia at Ta of 4 degrees C by inhibition of non-shivering thermogenesis.     

Effects of ICI 141,292 on exercise tachycardia and isoprenaline-induced beta-adrenoceptor responses in man.

The beta-adrenoceptor blocking properties and cardioselectivity of ICI 141, 292 were investigated in healthy male subjects. Seven subjects received in random order oral doses of ICI 141,292 20, 50, 100, 200 and 400 mg, atenolol 50 and 100 mg and placebo. ICI 14 292 had no effect on supine heart rate which was reduced by atenolol 100 mg. ICI 141,292 50, 100 and 200 mg had no effect on standing heart rate which was reduced by 400 mg at 2 h. Both doses of atenolol caused greater reductions. The maximum percent reduction of an exercise tachycardia after ICI 141,292 200 mg (23.9 +/- 3.7%) and 400 mg (24.3 +/- 5.2%) were similar to atenolol 50 mg (27.3 +/- 4.7%) but less than atenolol 100 mg (30.8 +/- 2.9%) (P less than 0.02). Six subjects received in random order single oral doses of ICI 141,292 100, 200 and 400 mg, atenolol 50 mg, propranolol 40 mg and placebo. Following each dose each subject received graded infusions of isoprenaline sulphate until heart rate increased by 40 beats min-1. Dose-response curves were constructed for the changes in heart rate, finger tremor, blood pressure and forearm blood flow produced by each infusion. At the 4 micrograms min-1 dose of isoprenaline, ICI 141,292 200 mg caused more attenuation than atenolol 50 mg but less than propranolol 40 mg in the changes of heart rate, diastolic blood pressure and finger tremor (P less than 0.02). ICI 141,292 400 mg caused more attenuation of the changes of all parameters than atenolol 50 mg but less attenuation of the changes in diastolic blood pressure and finger tremor than propranolol 40 mg (P less than 0.02). These results indicate that ICI 141,292 is a cardioselective beta-adrenoceptor antagonist with partial agonist activity.     

Beta-adrenoreceptor blockade attenuates heat-induced tachycardia,but not the tolerance to the stress.

Ten healthy males (age 34 +/- 3 yr 9 SE) underwent 40 min of heat exposure (WD 39.7.C) after 2 hours of ingesting 120 mg of Propranolol (Inderal; ICI), or a placebo, in a random manner, the exposures being about a week apart. That there was no placebo effect was ensured by giving a control run (no medication). In the placebo trials, the end-experiment heart rate had increased by 52%, while after propranolol the increase was only 43%. Regression analysis showed that with the placebo, the HR increased by 22 beats/min/o rise in core (aural) temperature, while with propranolol, the rise (14 beats/min) was significantly lower (P < 0.02). The various heat strain indices viz the Craig's Index, the Body heat storage (Kilocals/m2/hr), and the effective heat storage were also similar for both the treatments. We conclude that beta-adrenoreceptor activity plays a significant role in producing tachycardia of heat exposure in humans, but blocking this activity with propranolol does not affect tolerance to heat stress.     

A dose-ranging study to evaluate the beta-adrenoceptor selectivity of single doses of betaxolol.

1. Six normal subjects were given single oral doses of betaxolol 10 mg (B10), 20 mg (B20), 40 mg (B40), 80 mg (B80), propranolol 40 mg (P40), or placebo (PL) in a single-blind randomised cross-over design. 2. beta 1-adrenoceptor blockade was assessed by reductions in exercise heart rate. Betaxolol produced dose-related reductions in exercise heart rate (beats min-1) up to a ceiling at B40, after which B80 showed a lesser effect: (158 +/- 8 PL, 128 +/- 3 B10, 123 +/- 2 B20, 116 +/- 4 B40, 136 +/- 10 B80, 135 +/- 4 P40). All doses of betaxolol (except B80) produced greater reductions compared with P40: (B10 P less than 0.001, B20 P less than 0.005, B40 P less than 0.001). 3. beta 2-adrenoceptor blockade was assessed by attenuation of finger tremor and cardiovascular responses to graded infusions of i.v. isoprenaline. Dose-response curves were constructed and the doses required to increase heart rate by 25 beats min-1, finger tremor by 200%, calf blood flow by 0.5 ml dl-1 min-1, and decrease diastolic blood pressure by 10 mm Hg, after each treatment were calculated. These were then compared with placebo responses and expressed as dose-ratios. 4. Dose-ratios for finger tremor showed significant attenuation by all doses of betaxolol (compared with PL): B10 1.5 +/- 0.18 (P less than 0.05), B20 2.62 +/- 0.45 (P less than 0.005), B40 2.55 +/- 0.33 (P less than 0.001), B80 2.48 +/- 0.48 (P less than 0.01); and by P40 6.49 +/- 1.12 (P less than 0.001).(ABSTRACT TRUNCATED AT 250 WORDS)     

Characteristics of sustained tremor induced by nicotine in pilocarpine-treated animals

Sustained tremor (nicotine pilocarpine tremor) was produced by the administration of nicotine to pilocarpine pretreated mice and rats. and its characteristics were studied. Nicotine pilocarpine tremor was composed of tremor of the head and limbs and occasional sharp head movements up and backwards. Pilocarpine caused hyperthermia in most of the rats kept in a high ambient temperature (30 32 C) and also induced hypothermia under normal conditions (22 ± 2 C). Nicotine produced the sustained tremor only in rats which showed a rise in body temperature by pilocarpine pretreatment. In mice pretreated with pilocarpine, nicotine produced the sustained tremor under normal conditions as well. The time course of nicotine elimination from brain was dissociated from that of the intensity and duration of the sustained tremor. Atropine, nicotinolytic drugs, promethazine, phenobarbital and propranolol blocked the induction of nicotine-pilocarpine tremor. l-Dihydroxyphenylalanine, α-methyldopa, reserpine and tolazoline were not effective.It is suggested that nicotine-piloearpine tremor does not solely result from the inhibition of hepatic drug metabolism by pilocarpine, and that the central cholinergic system might be involved in the induction of nicotine pilocarpine tremor.     

Characterization of the beta-adrenoreceptors which mediate the isoprenaline-induced changes in finger tremor and cardiovascular function in man

Summary We have studied the contribution of beta₁- and beta₂-adrenoceptors to the isoprenaline-induced changes in heart rate, blood pressure, forearm blood flow, peripheral vascular resistance, and finger tremor. This was achieved by a comparison of the effects of atenolol 50 mg, ICI 118551 25 mg, propranolol 80 mg, atenolol 50 mg combined with ICI 118551 25 mg, propranolol 80 mg combined with ICI 118551 25 mg, and placebo.Atenolol 50 mg and ICI 118551 25 mg caused similar attenuations in the isoprenaline-induced changes in heart rate and diastolic blood pressure, but the responses after the combination of atenolol and ICI 118551 were similar to those after propranolol 80 mg.There was no difference in the forearm blood flow responses to isoprenaline after atenolol 50 mg and ICI 118551, but atenolol 50 mg did not reduce peripheral vascular resistance compared with placebo. Both responses after treatment with atenolol combined with ICI 118551 were similar to those after propranolol 80 mg.Finger tremor responses to isoprenaline were antagonized by ICI 118551 alone and in combination with propranolol and atenolol but not by atenolol alone, suggesting that the response is beta₂-adrenoceptor-mediated.We conclude that the cardiovascular responses to isoprenaline are mediated by both beta₁- and beta₂-adrenoceptors, whereas the finger tremor response is mediated by beta₂-adrenoceptors.     

Physiological response to propranolol and diazepam in chronic anxiety

1 Twelve chronically anxious psychiatric out-patients, comprising six with somatic anxiety and six with psychic anxiety, were treated with (±)-propranolol, diazepam and placebo for one week each in flexible dosage using a balanced cross-over experimental design.

2 After each treatment, in addition to ratings completed by patient and psychiatrist, finger tremor, EEG, averaged auditory evoked response, skin conductance, heart and respiratory rate were measured.

3 Diazepam significantly increased the amount of fast activity (13.5-26 Hz) in the EEG but produced few peripheral effects apart from a reduction in finger tremor.

4 Propranolol had no central physiological effects but reduced both pulse rate and finger tremor.

5 The physiological effects of propranolol in chronic anxiety are different from those of diazepam and therapeutic benefit appears to be due to a direct effect on certain somatic symptoms.

     

Enhancement of physiological finger tremor by intravenous isoprenaline infusions in man: evaluation of its role in the assessment of beta-adrenoceptor antagonists.

Graded intravenous isoprenaline infusions produce dose-related increases in finger tremor. The dose-response curves constructed with intra-arterial or intravenous isoprenaline behave similarly in the presence of both atenolol 50 mg and propranolol 40 mg. In Five subjects, practolol 120 mg, atenolol 50 mg, propranolol 40 mg and sotalol 200 mg reduced exercise heart rate by 20.2 +/- 2.3, 21.4 +/- 1.8, 17.4 +/- 2.5, 23.9 +/- 3.6% respectively: the differences were not significant. The corresponding dose-ratios for reduction of an isoprenaline tachycardia were 2.8, 2.3, 19.1 and 16.9 respectively. At doses which had comparable effects on an exercise tachycardia, the non-selective beta-adrenoceptor antagonists, propranolol 40 mg and sotalol 200 mg, attenuated the finger response to isoprenaline (dose ratios 33.3 and greater than 25.0 respectively) more than the beta 1-selective adrenoceptor antagonists, practolol 120 mg and atenolol 50 mg (dose ratios 1.0 and 2.3 respectively). In two out of five subjects, dose-response curves could not be constructed with sotalol, either at a dose of 200 or 100 mg. The enhancement of physiological finger tremor by intravenous infusions of isoprenaline may be useful in the investigation of beta 2-adrenoceptors and their antagonists in man.     

Clonidine-induced hypothermia: Possible involvement of cholinergic and serotonergic mechanisms

The thermoregulatory effects (including metabolic, vasomotor and respiratory activities) produced by an injection of clonidine (1-3 micrograms in 0.5 microliter) into the preoptic anterior hypothalamus were assessed in conscious rats at ambient temperatures (Ta) of 8, 22 and 30 degrees C. Intrahypothalamic administration of clonidine caused a dose-dependent fall in rectal temperature at Ta 8 degrees C and 22 degrees C. The hypothermia in response to clonidine was due to decreased metabolic heat production and/or cutaneous vasodilation. There was no change in respiratory evaporative heat loss. The clonidine-induced hypothermic response was attenuated by pretreatment of the rats with either 5,7-dihydroxytryptamine (10 micrograms, administered intrahypothalamicly, 14 days before clonidine injection), yohimbine (0.2 microgram, administered intrahypothalamicly, 10 min before clonidine injection), cyproheptadine (1 microgram, administered intrahypothalamicly, 10 min before clonidine injection), or atropine (0.1 microgram, administered intrahypothalamicly, 10 min before clonidine injection). The data indicate that clonidine may act on alpha-adrenoceptors located on a serotonin-acetylcholine pathway within the preoptic anterior hypothalamus to induce hypothermia by promoting a reduction in metabolic heat production and/or an enhancement in dry heat loss in rats.     

Effect of high ambient temperature on the kinetics of the pupillary light reflex in healthy volunteers.

Miotic responses to brief light stimuli were studied in healthy volunteers under two ambient temperature conditions, 22 degrees C and 40 degrees C. The latency and amplitude of the light reflex did not differ between the two conditions, but the recovery time of the reflex was significantly shorter under the 40 degrees C condition than under the 22 degrees C condition. The results are consistent with the hypothesis that exposure to high ambient temperature results in an increased sympathetic drive to the iris dilator muscle but does not influence the parasympathetic light reflex.     

Assessment of airways, tremor and chronotropic responses to inhaled salbutamol in the quantification of beta 2-adrenoceptor blockade.

1. The purpose of the study was to assess and compare the effects of inhaled salbutamol on heart rate (HR), finger tremor (Tr) and specific airways conductance (sGaw) in the measurement of beta 2-adrenoceptor blockade in normal subjects. 2. Five healthy volunteers were given oral doses of atenolol 50 mg, 100 mg, 200 mg (A50, A100, A200), propranolol 40 mg (P40) or identical placebo (P1) in a single-blind crossover design. 3. Three hours after drug ingestion, dose-response curves were constructed using cumulative doses of inhaled salbutamol: 200 micrograms, 700 micrograms, 1700 micrograms, 3200 micrograms, 6200 micrograms. HR, Tr and sGaw were measured at each dose increment, made every 20 min. 4. Increasing doses of atenolol were associated with progressive reduction in salbutamol induced beta-adrenoceptor responses. The greatest attenuation occurred with propranolol. These effects on beta-adrenoceptor responses were similar for HR, Tr and sGaw. Geometric mean dose ratios (compared with placebo) for A50, A100, A200 and P40 were as follows HR: 1.98, 2.75, 4.29; Tr: 1.60, 3.78, 6.34, 80.50; sGaw: 1.08, 4.35, 12.30, 66.0 (no dose ratio was obtained for HR with P40). 5. These results showed that atenolol and propranolol attenuated the effects of salbutamol on HR to a similar degree as Tr and sGaw. Furthermore, the variability was least in the measurement of chronotropic responses, suggesting that this may be used to quantify beta 2-adrenoceptor antagonism. The beta 1-adrenoceptor selectivity of atenolol was a dose-dependent phenomenon, although the beta 2-adrenoceptor blockade of A200 was much less than with P40.     

Effect of ambient temperature on thermoregulation in rats following preoptic/anterior hypothalamic injection of physostigmine

This experiment was designed to study the effect of ambient temperature (Ta) on the thermoregulatory response after the injection of the acetylcholinesterase blocking agent, physostigmine, into the preoptic/anterior hypothalamic area (POAH) of the rat. Three doses of physostigmine (3.0, 30.0 and 60.0 micrograms) were injected in a volume of 1.0 microliter in the preoptic/anterior hypothalamic area of unrestrained rats at three different ambient temperatures (15, 25 and 35 degrees C). Brain temperature (Tbr) and gross changes in behavior were monitored continuously throughout the duration of each experiment. Physostigmine induced hypothermia at ambient temperatures of 15 and 25 degrees C but not at 35 degrees C. Immediately prior to and during the hypothermic response the animals displayed behavioral reflexes such as fur licking and a sprawled posture which presumably enhanced heat loss. Generally, soon after the peak of the hypothermic response (approximately 30 min), the rats displayed heat-conserving behavior (huddled position, piloerection of the fur). These data indicate that the activity of cholinergic synapses within the preoptic/anterior hypothalamic area increases with decreasing ambient temperature. The behavioral observations suggest some role for the cholinergic system in the activation of heat-dissipating responses in the rat.     

Paradoxical effects of exogenous norepinephrine on cold-induced thermogenesis in the rat

The effect of norepinephrine (NE, 250 microgram/kg IP) on thermoregulatory behavior of rats in a cold environment was tested. Norepinephrine produced an increase in operant responding for heat reward but a decrease in core temperature. Since animals compensate behaviorally for alterations in autonomic thermoregulation, this suggested that NE might inhibit cold-induced thermogenesis, an effect contrary to the expected action of this agent. A second experiment showed that NE increased oxygen consumption when rats were tested at 25 degrees C as expected, but decreased oxygen consumption when tested at 5 degrees C. The beta-adrenoceptor antagonist propranolol decreased oxygen consumption both at 25 and at 5 degrees C as expected. These results suggest that the thermogenic effect of NE is highly dependent on ambient temperature.     

Effects of cholecystokinin octapeptide on thermoregulatory responses and hypothalamic neuronal activity in the rat

Rats were chronically implanted with a hypothalamic cannula to allow chemical stimulation of the hypothalamus on the conscious animals in repeated experiments. Direct administration of cholecystokinin octapeptide (CCK-8) (20-60 ng) into the preoptic anterior hypothalamic area caused a dose-related fall in rectal temperature at ambient temperatures of 8 degrees C and 22 degrees C. The hypothermia induced by CCK-8 was produced by a decrease in metabolism at an ambient temperature of 8 degrees C, whereas at 22 degrees C, it was caused by both a decrease in metabolism and an increase in cutaneous temperature. However, at an ambient temperature of 30 degrees C, intrahypothalamic administration of CCK-8 caused an insignificant change in thermoregulatory responses. Furthermore, neither intrahypothalamic injection of 0.9% saline nor intraperitoneal injection of CCK-8 (60 ng) had any effect on thermoregulatory responses at the ambient temperatures of 8 degrees-30 degrees C studied. Under urethane anaesthesia, 59 single neurons in the preoptic anterior hypothalamic area were examined in 29 rats. Each animal was subjected to scrotal warming or cooling and to the administration of CCK-8. Microiontophoretic application of CCK-8 resulted in inhibition of the majority (75%) of cold-responsive neurons as well as excitation of the majority (77.8%) of warm-responsive neurons recorded in the preoptic anterior hypothalamic area. However, the majority (69%) of thermally unresponsive cells were not affected by CCK-8 application. The data indicate that CCK-8, when administered intrahypothalamically, excites warm-responsive neurons and inhibits cold-responsive neurons within the preoptic anterior hypothalamic area to induce hypothermia by promoting an increase in heat loss and a decrease in heat production.     

The comparative effects of ICI 118551 and propranolol on essential tremor.

1. The effects of the selective beta 2-adrenoceptor antagonist ICI 118551 on essential tremor, heart rate and blood pressure were compared with those of propranolol. 2. ICI 118551 (150 mg daily for 7 days) and propranolol (120 mg daily for 7 days) were about equally effective in reducing essential tremor (by about 40%) and were more effective than placebo. 3. When compared with the effect of placebo, propranolol reduced blood pressure and exercise heart rate whereas ICI 118551 had no significant effect on blood pressure and produced a small but significant reduction in exercise-induced tachycardia. 4. ICI 118551 may be useful in the management of essential tremor while having fewer cardiovascular side-effects than non-selective beta-adrenoceptor antagonists.     

An assessment of physiological finger tremor as an indicator of beta-adrenoceptor function.

Physiological finger tremor has been assessed as an indicator of beta-adrenoceptor function. Tremor was not correlated with the sex, age, weight or height of the subjects and was stable over 5 min when the hand and fingers were held horizontally. It was not increased by mental arithmetic, the Valsalva manoeuvre or 3 min exercise. Satisfactory dose-response curves could be constructed for the isoprenaline enhanced increases in finger tremor. In six subjects, practolol 120 mg produced a small shift to the right of the isoprenaline dose-response curve for finger tremor (dose ratio 2.1) but propranolol 40 mg was seven times more effective (dose ratio 17.1). Physiological finger tremor appears to be a stable parameter which may be useful in the investigation of the selectivity of beta-adrenoceptor blocking drugs.     

Differences between the effect of prazosin and lysine-acetylsalicylate on some thermoregulatory parameters in nonfeverish rabbits

Thermoregulatory responses to prazosin and lysine-acetylsalicylate (LAS) were investigated in afebrile rabbits at different ambient temperatures, i.e. at 5, 21 and 28 degrees C. In cold as well as in heat prazosin significantly inhibited the metabolic rate. This effect was accompanied by falls in rectal temperatures, particularly at the ambient temperature of 5 degrees C. Increases in ear skin temperatures became visible only when this drug was used in rabbits maintained in the thermoneutral environment. On the other hand LAS in all tested conditions indicated a marked metabolic activity associated with an intensified respiratory heat loss. As a consequence, the rabbits responded with slight increases in body temperature. The possible mode of thermoregulatory activity of prazosin is being considered in confrontation with that of LAS.     

Seasonal differences in finger skin temperature and microvascular blood flow in healthy men and women are exaggerated in women with primary Raynaud's phenomenon

AIMS: Patients with primary Raynaud's phenomenon (PRP) have more severe symptoms in the winter. The aetiology of this is more complex than simply increased vasoconstriction in response to the immediate ambient temperature. The aim of this study was to investigate differences in skin temperature (Tsk), microvascular blood flow and responses to endothelium-dependent and independent vasodilators in healthy controls, and women with PRP under identical environmental temperatures but in different seasons. METHODS: Ten women with PRP were compared with age matched women (10) and men (10). Finger skin responses were recorded immediately on arrival, after stabilizing in a temperature regulated laboratory at 22-24 degrees C, and at matched warm (35 degrees C) and cold (15 degrees C) Tsk in the winter and summer. Baseline red blood cell flux (r.b.c. flux), and the change in flux in response to iontophoresis of acetylcholine (ACh) and sodium nitroprusside (SNP) were recorded by laser Doppler fluxmetry at the warm and cold Tsk. RESULTS: Arrival Tsk were significantly cooler for all subjects during the winter (mean seasonal difference -2.6 degrees C, P < 0.0001), and markedly colder in subjects with PRP (mean seasonal difference -3.5 degrees C, P < 0.0005). Statistically significant seasonal differences persisted in all subjects at stable Tsk despite an identical laboratory temperature (mean difference 1.3 degrees C, P < 0.0001). To achieve comparable controlled finger Tsk a significantly colder local environment was required for male controls (mean of -2.1 degrees C, P < 0.0001), and a significantly warmer environment for subjects with PRP (mean of + 2.4 degrees C, P < 0.0001) compared with female controls. This needed to be warmer in the winter, by a mean of 2.4 degrees C, than the summer for all subjects. Vasodilatation in response to ACh, but not SNP, was significantly smaller (P < 0.0001) in the PRP group compared with the female controls for all visits, with most of this difference arising in the winter visits (P < 0.01). CONCLUSIONS: There is a seasonal and persistent influence on finger Tsk, and microvascular blood flow in healthy men and women, which modifies the observed responses to immediate changes in finger Tsk. The seasonal differences are greater in women than men, and are further exaggerated in women with PRP, in whom this is associated with reduced endothelium-dependent vasodilatation.     

Depletion of brown fat norepinephrine content by acute cold exposure and adrenoceptor blockade

Experiments were conducted to characterize the effects of acute cold exposure, with and without adrenoceptor blockade, on intrascapular brown adipose tissue (IBAT) and adrenal catecholamine content in male Sprague-Dawley rats. Groups of animals with indwelling temperature transmitters were tested following treatment with saline, the alpha-adrenoceptor blocker phentolamine, the beta-adrenoceptor blocker propranolol, combined blockade with phentolamine plus propranolol, and the ganglionic blocker chlorisondamine. IBAT norepinephrine (NE) content was not affected in animals tested at 22 degrees C, but was reduced in 4 degrees C-exposed animals treated with phentolamine (-57%), phentolamine plus propranolol (-97%), and chlorisondamine (-42%). Adrenal NE and epinephrine (EPI) content were not altered by the treatments at 4 degrees C or 22 degrees C. None of the treatments affected the temperature of animals at 22 degrees C, but significant hypothermia occurred at 4 degrees C after chlorisondamine (-2.3+/-0.3 degrees C) and the combination of phentolamine and propranolol (-1.5+/-0.4 degrees C). These results suggest that cold exposure alone did not affect IBAT NE content, but when cold exposure was combined with adrenoceptor blockade, the sympathetic activation was sufficient to cause a reduction in IBAT NE content. In addition, alpha- and beta-adrenoceptor-mediated mechanisms contribute to the maintenance of core temperature. However, both alpha- and beta-receptor mechanisms had to be interrupted before a deficit in body temperature was detected.