The Effect Of Preoptic Area Lesioned And Sinoaortic Denervation On Hypothermia Induced By Peripheral Administration Of Arginine Vasopressin In Rats

A number of studies have demonstrated that the arginine vasopressin(AVP) plays an important role in thermoregulation. Central administration of AVP could cause hypothermic responses in normal mammals. Peripheral administration of AVP also causes a reduction in normal core temperature. We found that endogenous AVP, acting through V1 a receptor, could be involved in tonic thermoregulatory processes, because V1 a receptor antagonist could elevate core temperature during the light period. Several studies have assessed the mechanism by which AVP evokes the hypothermia. Evidence suggests that the ionotropic receptors of L-glutamate in the central nervous system participate in peripheral AVP-induced hypothermia by affecting heat loss through the tail. In addition, there is also evidence showing that baroreceptor re?exes are involved in the control of core and skin temperatures. Our studies suggest that peripheral AVP-induced hypothermia attributed to the suppression of brown adipose tissue(BAT)thermogenesis and the increase of saliva spreading for evaporative heat loss.BAT thermogenesis is a significant component of the homeostatic repertoire to maintain body temperature during the challenge of low environmental temperature in many species from mouse to man. Neural activity of sympathetic nerve innervating brown adipose tissue(BAT sympathetic nerve activity) plays an important role in thermogenesis. However, little is known about the AVP-induced hypothermic response and its relationship with BAT sympathetic nerve activity. Therefore, we first assessed the effects of peripheral administration of AVP on core temperature and BAT temperature, and its relationship with BAT sympathetic nerve activity. Subsequently,we examined the effect of preoptic area(POA) lesioned on AVP-induced hypothermia and BAT sympathetic nerve activity in the rat, and the effect of sinoaortic denervation on AVP-induced hypothermia. Finally, we examined the effect of intraperitoneal injection of AVP on LPS-induced fever in rats and BAT sympathetic nerve activity. The purpose of the present study was to determine AVP-induced hypothermic response and its relationship with BAT sympathetic nerve activity.PartⅠ The effect of preoptic area lesioned on AVP-inducedhypothermia in rats and its relationship with sympathetic nerveactivity innervating brown adipose tissue ObjectivesPrevious studies have demonstrated that the administration of AVP induces hypothermic response in rodents and other mammals, but little is known about the effects of preoptic area lesioned on AVP-induced hypothermia and BAT sympathetic nerve activity. Therefore, in the present study, we determined the effect of preoptic area lesioned on AVP-induced hypothermic response in the rat and its relationship with BAT sympathetic nerve activity.MethodsAll experiments were used the Specific Pathogen Free(SPF) adult male Sprague Dawley(SD) rats weighing 200-340 g, put the rats in containing wood packing of a single plastic cage breeding, animals were in a state of free food into the water and free activities.(1)Rats were submitted to kainic acid(KA) lesioning of the POA. Core temperature and motor activity were monitored by telemetry at an ambient temperature of 22℃. Rats were dosed intraperitoneally at 10:00 h with AVP(10 ug/kg) or saline(the same volume).(2)Sympathetic nerve innervating interscapular BAT was exposed through dorsal incision. The distal end of the nerve was ligated, and then hooked up with a pair of silver wire electrodes for recording the sympathetic nerve activity innervating brown adipose tissue. Nerve signals were recorded by BL-420 S Data Acquisition and Analysis System Performance of Chengdu Taimeng Sorftware Co.LTD.Results(1) In sham-operated rats, treatment with 10 ug/kg AVP underwent a significant drop in core and BAT temperature at 40 min after administration. However, POA lesioned rats dosed with AVP also had a decrease in core and BAT temperature at 40 min after administration, but the decrease was significantly attenuated than that of sham-operated rats.(2) Sympathetic nerve activity rapidly decreased after peripheral injection of AVP, with the greatest level of suppression(31.6%) occurring at 30 min.Approximately 120 min after dosing, sympathetic nerve activity recovered toward baseline levels.(3) POA lesioned attenuated the suppressive effects of intraperitoneal injection of AVP on BAT sympathetic nerve activity, with the greatest level of suppression(23.1%) occurring at 30 min after AVP. Approximately 75 min after dosing,sympathetic nerve activity recovered toward baseline levels.Conclusions(1) The POA is one of the important central thermoregulation, POA lesioned attenuated hypothermia induced by intraperitoneal injection of AVP, suggesting that intraperitoneal injection of AVP may through the blood brain barrier "leak" POA caused hypothermic responses. After POA lesioned did not completely inhibit AVP-induced hypothermia indicating that there may be other ways involve in the hypothermic effect of peripheral vasopressin.(2)The level of BAT sympathetic nerve activity was significantly reduced by intraperitoneal injection of AVP. However, POA lesioned also attenuated the suppressive effects of intraperitoneal injection of AVP on BAT sympathetic nerve activity. Therefore, we conclude that POA lesioned attenuated the effects of peripheral vasopressin on core temperature and BAT sympathetic nerve activity in the rat, and that POA may be involved in these effects.PartⅡ Effect of sinoaortic denervation on hypothermia induced by peripheral administration of AVP in ratsObjectivesThere is evidence showing that the cutaneous sympathetic vasoconstrictor tonus is barosensitive and that stimulation of baroreceptors modulates heat loss through the tail.Therefore, we examined the effect of sinoaortic denervation on AVP-induced hypothermia. The aim of this study was elucidate whether the AVP-induced hypothermia could result from activation of the sinoaortic baroreflex.MethodsAfter completion of transmitter implantation, a midline incision was made in the ventral region of the neck, cervical sympathetic nerves, and the carotid sheath weresectioned. The carotid bifurcations and carotid branches were stripped of fibers connectives tissues and painted with a small amount of phenol(10%) in ethanol.Sham-operated rats was performed by making a longitudinal incision at the cervical region. Core temperature and motor activity were monitored as described above.ResultsIn Sham denervation rats, the level of core temperature was significantly reduced by intraperitoneal injection of AVP. The mean core temperature was 1.95±0.23℃ lower than control levels at 40 min after administration. However, sinoaortic denervation rats showed an attenuated AVP-induced decrease in core temperature compared to sham denervation rats. The mean core temperature was only 1.26±0.32℃ lower than control levels at 40 min after administration. Administration of the saline led to a transient elevation in core temperature that were attributed to the stress of handling and injection procedure.ConclusionsSinoaortic denervation attenuated hypothermia induced by intraperitoneal injection of AVP, suggesting that sinoaortic baroreceptors(non-thermoregulatory reflex)would involve in the hypothermic effect of peripheral vasopressin.Part Ⅲ The effect of intraperitoneal injection of AVP on lipopolysaccharide-induced fever in rats and its relationship with sympathetic nerve activity innervating brown adipose tissue ObjectivesObjectivesCentral infusion of AVP to the febrile rat elicits a marked antipyretic response associated with a decrease in heat production, an increase in heat loss, and subsequent lowering of core temperature. However, little is known about the effect of intraperitoneal injection of AVP on lipopolysaccharide(LPS)-induced fever in rats and its relationship with BAT sympathetic nerve activity. Therefore, we examined the effect of intraperitoneal injection of AVP on LPS-induced fever in rats and BAT sympathetic nerve activity.MethodsThe core temperature and motor activity were measured by telemetry in adult male Sprague-Dawley rats at an ambient temperature of 22℃ during a 12 h light:12 h dark photoperiod. Effect of 10 ug/kg AVP or physiological saline(the same volume) given90 min after rats were dosed intraperitoneally with saline(1 ml/kg) or LPS(50 ug/kg) at10:00 h.(2) BAT sympathetic nerve activity was performed as described above.Baseline measurements of BAT sympathetic nerve activity was made for 60 min just before intraperitoneal administration of 50 ug/kg LPS or saline(1ml/kg). After 90 min,Animals were given saline or 10 ug/kg AVP by intraperitoneal injection, BAT sympathetic nerve activity was recorded for 510 min.ResultsIntraperitoneal administration of LPS(50 ug/kg)evoked a biphasic febrile response.After a 90 min latency, core tmperature rose to a first fever peak(37.86 ±0.21℃) at 160 min and a second fever peak(38.58±0.18℃) at 270 min after LPS.(2) Administration of AVP quickly reversed the febrile responses of LPS and led to a 1.82℃ drop in core temperature. The period of hypothermia persisted for 105 min. At the same time, AVP given to control animals led to a 2.32℃ decrease in core temperature that persisted for over 120 min. It was noted that recovery from AVP-induced hypothermic responses of LPS was more rapid compared with control animals.(3)Sympathetic nerve activity increased markedly at 90 min after intraperitoneal injection of LPS, and it was evoked a biphasic elevation response. Sympathetic nerve activity increased to a first peak at 160 min and a second peak at 280 min after LPS.(4) Intraperitoneal administration of AVP(10 ug/kg) attenuated significantly the excitatory effects of LPS on BAT sympathetic nerve activity.Conclusions(1)The key observations in this study are:(1) Intraperitoneal injection of LPS(50ug/kg) evoked a biphasic febrile response in rats and related with BAT sympatheticnerve biphasic elevation activity.(2)Peripheral administration of AVP(10 ug/kg)attenuated significantly the excitatory effects of LPS on BAT sympathetic nerve activity,suggesting that AVP-induced the antipyretic effect attributed to the suppression of BAT sympathetic nerve activity.