Central pathway for spontaneous and prostaglandin E₂-evoked cutaneous vasoconstriction

Abstract

Rathner JA, Madden CJ, Morrison SF. Central pathway for spontaneous and prostaglandin E2-evoked cutaneous vasoconstriction. Am J Physiol Regul Integr Comp Physiol 295: R343-R354, 2008. First published May 7, 2008 doi:10.1152/ajpregu.00115.2008.-A reduction of heat loss to the environment through increased cutaneous vasoconstrictor (CVC) sympathetic outflow contributes to elevated body temperature during fever. We determined the role of neurons in the dorsomedial hypothalamus (DMH) in increases in CVC sympathetic tone evoked by PGE2 into the preoptic area (POA) in chloralose/urethane-anesthetized rats. The frequency of axonal action potentials of CVC sympathetic ganglion cells recorded from the surface of the tail artery was increased by 1.8 Hz following nanoinjections of bicuculline (50 pmol) into the DMH. PGE2 nanoinjection into the POA elicited a similar excitation of tail CVC neurons (ϩ2.1 Hz). Subsequent to PGE2 into the POA, muscimol (400 pmol/side) into the DMH did not alter the activity of tail CVC neurons. Inhibition of neurons in the rostral raphé pallidus (rRPa) eliminated the spontaneous discharge of tail CVC neurons but only reduced the PGE2-evoked activity. Residual activity was abolished by subsequent muscimol into the rostral ventrolateral medulla. Transections through the neuraxis caudal to the POA increased the activity of tail CVC neurons, which were sustained through transections caudal to DMH. We conclude that while activation of neurons in the DMH is sufficient to activate tail CVC neurons, it is not necessary for their PGE2-evoked activity. These results support a CVC component of increased core temperature elicited by PGE2 in POA that arises from relief of a tonic inhibition from neurons in POA of CVC sympathetic premotor neurons in rRPa and is dependent on the excitation of CVC premotor neurons from a site caudal to DMH. rostral raphé pallidus; thermoregulation; fever; dorsomedial hypothalamus; preoptic hypothalamus IN BOTH HUMANS (19,20,43) and rats (53) cutaneous vasoconstrictor (CVC) tone regulates heat loss to the environment and contributes importantly to the maintenance of normal body temperature and to the development of fever. The essential role for the generation of PGE 2 in the preoptic area (POA) in the production of fever has led to the use of nanoinjections of PGE 2 into the POA to understand the neural pathways controlling thermoregulatory effectors during the febrile response. Similarly, observations of thermal effector responses elicited by changes in skin (T SK ) or core temperature (T C ) have provided important information on the central neural networks responsible for body temperature homeostasis. Such studies have been pursued most extensively with regard to the sympathetic neural regulation of non-shivering thermogenesis in rodent brown adipose tissue (BAT), a highly metabolic tissue in which heat production contributes significantly to the defense of body temperature in cold environments and to the elevation of body temperature during the febrile response. The neur...

A thermosensory pathway mediating heat-defense responses

“…The absence of evidence for brain sites intermediate between the POA and the rostral medullary raphe that are required for the POA efferent signaling for temperature-dependent CVC control supports the significance of the direct projection from POA neurons to the rostral medullary raphe as the efferent pathway for febrile and thermoregulatory control of cutaneous vasoconstriction (30,33,34). The present results do not exclude the possibility that warm-responsive LPBd neurons have axonal branches that could bypass the POA and provide thermosensory signals directly to sites, such as the rostral medullary raphe, in the efferent pathways controlling thermoregulatory effectors, but this possibility seems unlikely, because there are very few projections from the LPB to the rostral medullary raphe (14), and antagonizing glutamate receptors in the MnPO resulted in a nearly complete blockade of heat-defensive responses to skin warming or stimulation of LPBd neurons.…”

“…Recent findings on the efferent control of sympathetic CVC tone indicate that the effector signaling from the POA leading to temperature-dependent CVC control is mediated by the rostral medullary raphe including the rostral raphe pallidus (30), a site of sympathetic premotor neurons controlling skin blood vessels (31,32). The absence of evidence for brain sites intermediate between the POA and the rostral medullary raphe that are required for the POA efferent signaling for temperature-dependent CVC control supports the significance of the direct projection from POA neurons to the rostral medullary raphe as the efferent pathway for febrile and thermoregulatory control of cutaneous vasoconstriction (30,33,34).…”

Preoptic–Raphé Connections for Thermoregulatory Vasomotor Control

“…The rat's tail is a major organ of heat loss, and its circulation is regulated by sympathetic vasoconstrictor nerves under the control of the brain. Sympathetic premotor neurons controlling the tail circulation are located in the rostral medullary raphé (Smith et al, 1998;Tanaka et al, 2002Tanaka et al, , 2007Nakamura et al, 2004;Ootsuka et al, 2004;Ootsuka and Blessing, 2005;Ootsuka and McAllen, 2005) and to a lesser extent the rostral ventrolateral medulla (Tanaka et al, 2002;Ootsuka and McAllen, 2005;Rathner et al, 2008).…”

“…Under warm conditions, brain transection caudal to the preoptic area (Rathner et al, 2008) or neuronal inhibition in the preoptic area (Osborne and Kurosawa, 1994) induce tail vasoconstriction, indicating that the tail vasomotor supply is under tonic inhibitory regulation by preoptic neurons. We recently showed that neurons in two distinct preoptic loci contribute to this tonic inhibition; a rostromedial preoptic region (RMPO) surrounding the organum vasculosum of the lamina terminalis and the median preoptic nucleus (MnPO), and a preoptic region centered ϳ1 mm caudolaterally (CLPO) (Tanaka et al, 2009).…”

Histaminergic Modulation of Body Temperature and Energy Expenditure

“…It is believed that warm-sensitive neurons in PO/AH send excitatory signals to vasodilator neurons and inhibitory signals to vasoconstrictor neurons. PO/AH neurons controlling cutaneous blood flow project to the rostral medullary raphe region directly [26], suggesting that distinct populations of PO/AH neurons control thermogenesis and cutaneous vasomotion. This concept is supported by the observation that the two thermoregulatory mechanisms are activated at different threshold temperatures [27].…”