Physiological mechanisms of thermoregulation in reptiles: a review

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1 J Comp Physiol B (2005) 175: DOI /s REVIEW Frank Seebacher Æ Craig E. Franklin Physiological mechanisms of thermoregulation in reptiles: a review Received: 15 February 2005 / Revised: 29 April 2005 / Accepted: 20 May 2005 / Published online: 27 July 2005 Ó Springer-Verlag 2005 Abstract The thermal dependence of biochemical reaction rates means that many animals regulate their body temperature so that fluctuations in body temperature are small compared to environmental temperature fluctuations. Thermoregulation is a complex process that involves sensing of the environment, and subsequent processing of the environmental information. We suggest that the physiological mechanisms that facilitate thermoregulation transcend phylogenetic boundaries. Reptiles are primarily used as model organisms for ecological and evolutionary research and, unlike in mammals, the physiological basis of many aspects in thermoregulation remains obscure. Here, we review recent research on regulation of body temperature, thermoreception, body temperature set-points, and cardiovascular control of heating and cooling in reptiles. The aim of this review is to place physiological thermoregulation of reptiles in a wider phylogenetic context. Future research on reptilian thermoregulation should focus on the pathways that connect peripheral sensing to central processing which will ultimately lead to the thermoregulatory response. Keywords Body temperature Æ Evolution Æ Thermoreception Æ Endothermy Æ Ectothermy Æ Metabolism Æ Control Æ Heat Æ Cardiovascular Abbreviations TRP: Transient receptor potential Æ NO: Nitric oxide Æ NOS: Nitric oxide synthase Æ COX: Communicated by I.D. Hume F. Seebacher (&) Integrative Physiology, School of Biological Sciences A08, University of Sydney, Sydney, NSW 2006, Australia fseebach@bio.usyd.edu.au Tel.: Fax: C. E. Franklin School of Integrative Biology, The University of Queensland, St. Lucia, QLD 4072, Australia Cyclooxygenase enzyme Æ CPT: 8-Cyclopentyltheophylline Introduction The thermodynamic dependence of biochemical reaction rates makes thermal physiology the most pervasive component in the biology of animals. There are two principle, but not mutually exclusive, trajectories along which the thermal physiology of vertebrate animals has evolved. On the one hand, there is a trend towards regulating body temperature very precisely within narrow bounds regardless of environmental conditions (DiBona 2003). On the other trajectory, physiological/ biochemical reaction rates have evolved to be plastic within individuals and/or between populations and species with the result that functional rates are maintained despite considerable variation in body temperature (Guderley and St. Pierre 2002; Johnston and Temple 2002; Guderley 2004). In this review, we focus on the regulation of body temperature and the physiological mechanisms that facilitate thermoregulation, rather than thermal plasticity and temperature compensation of reaction rates. The opportunity for thermoregulation is limited in thermally homogenous environments, particularly in water where the large convection coefficients rapidly equalise thermal differentials between an animal and its environment. Except for those animals that are very large or extremely well-insulated, body temperature of aquatic organisms tends to equal that of the water, and aquatic animals compensate biochemically and physiologically for temporally varying body temperatures and/or their distribution is restricted to favourable climatic regions. On land, daily regulation of body temperature is facilitated by the heterogeneity of the thermal environment, and relatively low heat transfer rates in air. Thermoregulation is a complex process that must integrate sensing of temporal and spatial variation in the thermal environment with behavioural and physiological responses that

2 534 will result in a narrow range of body temperatures relative to operative temperatures fluctuations (Seebacher and Shine 2004). The aim of this review is to summarise recent research on physiological mechanisms of body temperature control, and to place reptiles within the broader framework of vertebrate thermoregulation. Many traits of vertebrates are evolutionarily conservative, and the future direction in the field of reptilian thermal physiology can be informed by the more intensive research efforts and resultant detailed knowledge of mammalian thermoregulatory mechanisms. In the past years, the characterisation of molecular mechanisms involved in thermoregulation, such as thermally sensitive proteins and the various roles of nitric oxide, have been particularly significant. Hence, we will review some of the more medically orientated literature on mammals along with recent work on reptiles. We will first provide a general summary of thermoregulatory mechanisms. Regulation of body temperature presupposes that animals are capable of sensing their environment, and of processing information. Hence, the second and third section will review thermoreception and set-points of body temperature regulation. In the final section we will discuss cardiovascular mechanisms of temperature control which are an essential component of thermoregulation in both endotherms and ectotherms. Regulation of body temperature The principle physiological basis of body temperature regulation in endotherms is the production of metabolic heat in combination with thermal insulation (Kauffman et al. 2001; Kvadesheim and Aarseth 2002; Seebacher 2003). Compared to ectotherms, increased metabolic heat production in endotherms is in part owing to a relative increase in metabolically active tissues liver, heart, and gastrointestinal systems (Fig. 1), to an increase in cellular density of mitochondria, and to the decoupling of metabolic pathways from ATP production (Else and Hulbert 1981; Else and Hulbert 1985; Brand et al. 1991). Specific decoupling mechanisms, such as leaky membranes and uncoupling proteins (Brand et al. 2004), lead to the electrochemical free-energy generated across the mitochondrial membrane to be dissipated as heat rather than converted into chemical energy by oxidative phosphorylation (Kadenbach 2003). Uncoupling proteins are well-known from mammals and birds (Nedergaard et al. 2001; Raimbault et al. 2001; Brand et al. 2004; Kabat et al. 2004) but have as yet not been reported from ectothermic reptiles. The proportion of polyunsaturated fatty acids in the composition of mitochondrial membranes is correlated with the activity of membrane bound proteins. Membrane composition may, therefore, be a principal mechanism that regulates dissipation of the proton gradient, and it may act as a metabolic pacemaker Fig. 1 Comparisons between a mammal and a reptile. Sodium pump concentrations (pmol mg protein 1 ) are not significantly different between cows and crocodiles, but the molecular activities (ATP/min) of the pumps are significantly greater in the cow (main graph; data from Wu et al. 2004). The mass of the major organs (ratio lizard:mouse shown) is significantly lower in reptiles than in mammals (inset; data from Else and Hulbert 1981) (Hulbert and Else 1999; Else and Hulbert 2003). Of particular interest is docosahexaenoic acid (DHA) which is an important modulator of membrane bound sodium pump activity (Turner et al. 2003). Na + K + ATPase concentrations are similar in microsomal membranes of a crocodile and a cow, but enzyme activities were 4 5 fold greater in the cow compared to the crocodile (Fig. 1). Delipidation of Na + K + ATPase and reconstitution with membranes across species (e.g. cow protein with crocodile membrane) provides direct evidence that protein activity is determined by the membranes (Wu et al. 2004). Additionally, endotherms have significantly greater concentrations of DHA and other polyunsaturated fatty acids compared to ectotherms (Brand et al. 1994; Wu et al. 2004) so that there is a correlation between protein activity and membrane fatty acid composition. Although internal heat production is negligible for thermoregulation in ectothermic reptiles, metabolic heat may be important for nest temperature regulation. Developing alligator embryos may produce sufficient metabolic heat to raise the temperature at the centre of an egg cluster to 2 3 C above that of an open arrangement of eggs (Ewert and Nelson 2003). Typically, however, reptiles thermoregulate behaviourally by exploiting their thermal environment resulting in body temperatures that fall within a narrow range for at least part of the day (Hertz 1992; Hertz et al. 1993; Seebacher et al. 2003; Seebacher and Shine 2004). Basking in the sun is one of the most typical thermal behaviours in reptiles (Cowles and Bogert 1944; Seebacher 1999; Gvozdik 2002), although exposure to sun may have functions other than thermoregulation. For example, the panther chameleon s (Furcifer pardalis) exposure to UV radiation functions at least partly in regulating endogenous

3 535 vitamin D 3 production (Ferguson et al. 2003; Ferguson et al. 2005). Photolytically produced vitamin D performs a number of physiological functions, including regulation of Ca 2+ metabolism and cell signalling (Boyen et al. 2002). Thermoreception The efficacy of behavioural thermoregulation depends on the capacity of animals to sense their thermal environment. Sensing of environmental temperatures would seem particularly important for animals that thermoregulate behaviourally because the targeted exploitation of different thermal microhabitats requires contrasting of environmental and internal temperatures (Cooper 2002). Specialised peripheral nerve endings that can respond to both constant and variable temperatures are known from several invertebrate and vertebrate taxa (Cesare and McNaughton 1996; Caterina et al. 1997; Viana et al. 2002; Brown 2003; Patapoutian et al. 2003; Viswanath et al. 2003). In mammals, temperature may be sensed by a family of transient receptor potential ion channels (TRP) that are gated by specific temperatures (Viswanath et al. 2003). These thermally activated TRPs are located within the free nerve endings in the skin, but are also found in the peripheral nervous system, brain, heart and liver (Patapoutian et al. 2003). Six thermally sensitive TRPs have been identified that each operate over distinct temperature ranges (Fig. 2). Other transducers that have been implicated in thermosensing in mammals include the two-pore domain K + channels (TREK-1; Caley et al. 2005). A different sensing mechanism exists in sharks where the electrosensitive ampullae of Lorenzini are capable of sensing changes in environmental temperature (Brown 2003). Gel-filled canals connect pores at the surface of sharks to the innervated ampullae situated subdermally. The gel has the thermoelectric properties of a semiconductor, thereby conveying thermal information from the skin pores to the nerve endings in the ampullae (Brown 2003). The pineal complex may act as a thermal sensor in reptiles (Lutterschmidt et al. 1997), but specific neural sensors associated with ion channels are not known from reptiles. A possible exception are boid and crotaline snakes that possess specific heat sensing organs (pit organs; de Cock Buning 1983). Pit organs are innervated by the trigeminal nerve in a sensory pathway that involves protein kinase C as the signal transducer (Moon et al. 2003), and are capable of detecting electromagnetic radiation from near UV to infrared (Moiseenkova et al. 2003). The function of pit organs is thought to lie primarily in prey detection and capture (de Cock Buning 1983; Shine and Sun 2002). The infrared receptors in the pit organs of the snake Trimeresurus flavoviridis are sensitive to temperature (Moon 2004), but their detection distance is very short (<0.005 m; Jones et al. 2001) which would make it quite ineffective for predation Fig. 2 Environmental sensing in vertebrates. a Heat stressed rattlesnakes, Crotalus atrox, with intact pit organs (before) had significantly greater success (proportion of all trials) in choosing a thermally benign habitat than snakes with blocked pit organs (blocked); when pit organs were unblocked (after), snakes regained the ability to choose the benign habitat. A success rate of 0.5 would be expected if choice was random. Data from Krochmal and Bakken (2003). b Alligators and crocodiles possess dome pressure sensors (blue arrow) on their head that are innervated by the trigeminal nerve (Soares 2002; photo of Crocodylus johnstoni by FS). c Mammals possess a family of transient receptor potential ion channels (TRPV1 4, TRPV8, ANKTM1) each of which has a different thermal sensitivity range. Data from Patapoutian et al. (2003) (Jones et al. 2001). Short detection distance could be advantageous for thermoreception associated with thermoregulation. Behavioural trials with the rattlesnake, Crotalus atrox, indicate that pit organs are used by the animals to detect thermally favourable microhabitats. When snakes in a maze were given the choice of a thermally stressful (40 C) or a benign (30 C) environment after being exposed initially to the stressful environment, snakes with pit organs that were experimentally blocked chose the benign refuge on significantly fewer occasions than snakes with intact pit organs (Krochmal and Bakken 2003; Fig. 2). This pattern of preferentially choosing thermal refugia persisted across 12 pit viper species all of which possess facial pits, but not in a true viper that lacks facial pits (Krochmal et al. 2004). Behavioural data therefore indicate that pit organs are multifunctional, and that thermoregulation

4 536 rather than prey detection may even have been the principle selection pressure leading to their evolution (Krochmal et al. 2004). Pit organs are the only known thermal sensors among non-avian reptiles, although crocodilians possess external pressure sensors, or dome pressure receptors (Soares 2002; Fig. 2). Dome pressure receptors are dome like structures located on the head of crocodilians that are covered externally by a considerably reduced keratin layer, and which are innervated by the trigeminal nerve (Soares 2002). The mechanisms of transduction of pressure stimuli within the receptors are unknown is it possible that dome receptors also sense heat maybe via a semiconductor mechanism? Body temperature set-points Body temperatures in thermoregulating reptiles may vary temporally within individuals between day and night and between seasons, and many species become inactive when preferred body temperatures are unattainable. Daily and seasonal fluctuations in behaviour and physiological functions of reptiles as well as of other vertebrates are regulated by the circadian system. The circadian system acts as an endogenous oscillator by integrating the hypothalamus, lateral eyes, the pineal complex (Tosini et al. 2001), and, at least in mammals, the retina (Sakamoto et al. 2004). Thermally inspired behaviour in reptiles may be hormonally directed, and melatonin in particular has been associated with thermoregulation. Melatonin is produced by the pineal gland and interacts with the thyroid gland, and it may directly influence secretions of thyroid hormone (Krotewicz and Lewinski 1994; Wright et al. 1996). Melatonin may act as an intermediary between optical signals, and behavioural and physiological responses (Axelrod 1974). Levels of melatonin characteristic to those produced in darkness have been observed to decrease the body temperature selected by a snake (Pituophis melanoleucus; Lutterschmidt et al. 1997; Fig. 3). Similar responses whereby selected body temperatures are influenced by concentration of melatonin occur in several species of reptile (e.g. Cothran and Hutchison 1979; Erskine and Hutchison 1981). Additionally, melatonin levels also vary seasonally and may, therefore, act to co-ordinate activity and thermoregulation with climatic conditions on a daily and seasonal time scale (Mendoc a et al. 1995; Tosini and Menaker 1996). Interestingly, however, intraperitoneal injections of melatonin did not affect body temperature selection of a nocturnal snake (Lamprophis fuliginosus) in a linear thermal gradient compared to control treatments (Lutterschmidt et al. 2002; Fig. 3). Thermoregulatory behaviour in toads also does not depend on melatonin (Sievert and Poore 1995), and these findings may indicate that there are fundamental differences in thermal control centers between diurnal and nocturnal ectotherms. Fig. 3 After treatment with melatonin, the diurnal bullnake Pituophis melanoleucus selected significantly lower body temperatures in a thermal gradient. In contrast, melatonin injection did not alter the body temperature selection of the nocturnal African house snake Lamprophis fuliginosus (Data from Lutterschmidt et al. 2002) Selected body temperatures may be influenced by environmentally induced changes in metabolic state. In particular, low blood oxygen concentrations, either brought about by intensive exercise or a hypoxic environment can result in lower body temperatures (anapyrexia) in ectotherms and endotherms (Wagner and Gleeson 1997; Steiner and Branco 2002; Petersen et al. 2003). Hypoxia increases adenosine release which may interact with receptors on the hypothalamus to effect a decrease in body temperature (Barros and Branco 1999). For example, the selected body temperature of the lizard Anolis sagrei is 34.8 C under normoxic conditions, but exposure to hypoxic conditions in a thermal gradient resulted in a significant 5 C drop in selected body temperatures. Similarly, mean selected body temperatures decreased by 4 C following exhaustive exercise. Intraperitoneal administration of the adenosine receptor antagonist 8-cyclopentyltheophylline prevented or substantially reduced the hypoxia or exercise-induced drop in mean selected body temperature (Petersen et al. 2003; Fig. 4). However, administration of the adenosine antagonist did not reduce selected body temperature during normoxia (Petersen et al. 2003), and the reduction in body temperature during hypoxia may be a mechanism to reduce O 2 consumption. Nitric oxide (NO), and the activity of nitric oxide synthase (NOS), is instrumental in the brain of mammals as a signalling molecule in the thermal response. Inhibition of NOS by injection of inhibitors directly into the lateral cerebral ventricle of rats caused a significant hyperthermia that was sustained for several hours (Mathai et al. 2004). Intravenous injection of the NOS inhibitor L-NAME did not affect thermoregulation, however, demonstrating that NO acts specifically in the brain (Mathai et al. 2004). Interestingly, inhibiting prostaglandin synthesis by administration of a non-steroidal anti-inflammatory drug (indomethacin) before the L-NAME treatment abolished the hyperthermic effect of NOS inhibition (Mathai et al. 2004). The activity of

5 537 Fig. 4 Oxygen limitation induces anapyrexia in the lizard Anolis sagrei. Body temperature selected in a thermal gradient was significantly lower in hypoxic air (10% O 2 ) compared to normoxia. Similarly, selected body temperatures were decreased following exhaustive exercise. Blockade of adenosine receptors with 8- cyclopentyltheophylline (CPT), however, significantly reduced the anapyrexia following hypoxia and exercise. Data from Petersen et al. (2003) cyclooxygenase enzyme (COX), which is responsible for prostaglandin synthesis, may be controlled by NO (Salvemini 1997), and the interaction between the indomethacin and L-NAME treatments (Mathai et al. 2004) show that the NOS NO COX control axis is important for thermoregulation in rats. The role of prostaglandins in body temperature control and fever in mammals is well-established (Feldberg and Saxena 1971), and direct injection of PGE 2 into the hypothalamic region of the rat brain causes an increase in the thermogenic response (Madden and Morrison 2004). Nitric oxide synthase is present in the brains of a turtle (Bru ning et al. 1994) and a lizard (Smeets et al. 1997), but whether it functions in thermoregulation remains unknown. Prostaglandins, on the other hand, alter the thermoregulatory set-point in an amphibian (Bicego et al. 2002) and a reptile (Bernheim and Kluger 1976) by mediating a behavioural fever response following injection of an exogenous pyrogen. In the toad, Bufo paracnemis, experimental lesions to the preoptic area of the brain abolishes the characteristic pyrogen-induced fever response (Bicego and Branco 2002), and it seems likely that the prostaglandin-mediated reaction is situated in the preoptic area. Additionally, both prostaglandins and nitric oxide are important in cardiovascular responses during thermoregulation in reptiles (see below; Seebacher and Franklin 2003; Seebacher and Franklin 2004a). Cardiovascular control of heat transfer The efficacy of behavioural thermoregulation is determined to a large extent by cardiovascular changes (Bartholomew and Tucker 1963; Grigg et al. 1979; Grigg and Seebacher 1999; Seebacher and Grigg 2001; Dzialowski and O Connor 2001). It is advantageous for reptiles that regulate body temperatures within a narrow range relative to environmental (operative) temperature fluctuations to control rates of heating and cooling while moving in a thermally heterogeneous environment (Seebacher 2000). Such control may be achieved by altering cardiac output and the distribution of blood flow in the body. Elevated cardiac output, achieved primarily by increase in heart rate in reptiles, and peripheral circulation will increase rates of transient heat transfer between animals and their environment (O Connor 1999; Seebacher 2000; Seebacher and Franklin 2004b). Hence, by increasing heart rates during heating and decreasing heart rates during cooling reptiles can exert control over heat exchange with the environment (Fig. 5). This pattern, known as heart rate hysteresis, has been described from all major lineages of reptile (Bartholomew and Tucker 1963; Grigg et al. 1979). Interestingly, in crocodiles (Crocodylus porosus) the magnitude of the hysteresis (i.e. difference in heart rate between heating and cooling) depends on the mode by which heat is transferred between the animal and its environment. The heart rate differential between heating and cooling is greatest during radiant heating, and heart rate changes in proportion to the heat load experienced at the animal surface (Franklin and Seebacher 2003; Fig. 5). By analogy, similar cardiovascular changes are the principle thermoregulatory mechanisms when endothermic body temperatures are within the thermal neutral zone (Romanovsky et al. 2002). Preferential blood flow to the limbs during heating, supported by increased cardiac output, may be one of the mechanisms by which differential rates of heating and cooling are achieved. Placing thermal insulation around the limbs of Iguana iguana during heating and cooling did not alter rates of heat exchange compared to a control group, but a significant interaction between heating/cooling and insulated/uninsulated limbs indicates that limbs may be important in determining rates of heating (Dzialowski and O Connor 2004). Feeding and digestion causes an increase in heart rate even beyond that resulting from heat. The additional cardiac output in postprandial Varanus exanthematicus did not, however, increase rates of heating and increased blood flow after a meal appeared to be directed to the gut without any thermoregulatory effect (Zaar et al. 2004). Heart rate hysteresis consists of two phases, one a very rapid (seconds) increase or decrease in heart rate in response to application or removal of heat, respectively, that occurs while body temperature remains stable. This rapid response, which may represent a neural reflex arc, is followed by a more gradual change in heart rate that is proportional to changes in body temperature, and during which heart rates during heating exceeds heart rate during cooling at any given body temperature (Franklin and Seebacher 2003). The rapid-response phase is at least partly controlled by cholinergic and b-adrenergic receptors, but autonomic blockade did not abolish the hysteresis pattern in a lizard (Pogona barbata, Seebacher and Franklin 2001). A second control system that may act either alongside or instead of the autonomic nervous

6 538 porosus, and heart rate hysteresis persisted even with double inhibition of nitric oxide synthase and cyclooxygenase enzyme (Seebacher and Franklin 2004a). Nitric oxide did play a role during heating and cooling in C. porosus, by buffering blood pressure against changes in heart rate during cooling (Seebacher and Franklin 2004a). The differences in the role of prostaglandins between lineages (Squamata [P. vitticeps] and Archosauria [C. porosus]) may indicate an evolutionary divergence of control systems. The existence of heart rate hysteresis during heating and cooling in a crustacean (Goudkamp et al. 2004) indicates that this phenomenon may have evolved alongside arterialisation of the vascular system in organisms with principle regulatory mechanisms in place. In the subsequent evolution of heart rate hysteresis as a thermoregulatory trait different mechanisms that control the cardiovascular system during thermoregulation may have taken precedence in different lineages. Conclusions and future directions Fig. 5 Reptiles control rates of heating and cooling by changing heart rates (fh) and cardiac output. a fh is significantly higher during heating compared to cooling (data from Seebacher and Franklin 2003). b Modelled body temperatures for different heart rates; increased heart rates lead to faster rates of heating and decreased heart rates slow cooling. Body temperatures were model according to methods in Seebacher (2000). c Changes in heart rate (D fh) during heating and cooling (excluding the reflex period) depend on the heat load received at the animal surface (curve: Y=6.41*1.06 x ; R 2 =0.74). Data from Franklin and Seebacher (2003) system are prostaglandins. Prostaglandin F 2a and prostacyclin cause a significant response in heart rate, and inhibition of prostaglandins abolishes the characteristic heart rate hysteresis response in the lizard Pogona vitticeps (Seebacher and Franklin 2003). In contrast, inhibition of cyclooxygenase enzyme did not affect heart rate differential during heating and cooling in Crocodylus Thermoregulation is an integrated process involving peripheral sensing, central processing, and co-ordination of response functions that will affect body temperature. Recent advances in thermal reception and temperature control in non-reptilian vertebrates, particularly in mammals, could inform the field of reptilian thermoregulation and guide future research efforts. The evolutionary conservatism of many traits among vertebrates suggests that there may exist a commonality of thermoregulatory mechanisms as well. Ectothermy is an ancestral trait and comparisons between modern taxa suggest that endotherms utilise many of the same principle mechanisms of thermoregulation as ectotherms (e.g. Else and Hulbert 1981). Knowledge of thermoregulation in reptiles is concentrated on behavioural and ecological aspects and, despite the recent advances reviewed here, some of the essential mechanisms that underlie the whole animal response remain poorly understood. There are several traits known to be important in thermoregulation of endotherms but not of ectothermic reptiles, e.g. uncoupling proteins, thermally sensitive proteins and neurons, and the central control function of NO and COX. At present, these differences probably reflect the disparate research efforts on the respective groups rather than evolutionary differences. Significant advances in understanding the evolution of thermoregulation will be made when similarities and differences between different groups of animals (endotherms ectotherms, avian non avian reptiles, vertebrates invertebrates, etc.) have been experimentally established. Selection pressures act on individual traits rather than on composite, whole animal responses (Woods and Harrison 2002). To understand the evolution of thermoregulation, it is essential to understand the mechanisms that underlie the thermal responses that are characteristic for each group.

7 539 Future research on reptilian thermoregulation should focus on the pathways that connect peripheral sensing to central processing which will ultimately lead to the thermoregulatory response. Sensing of the thermal environment is particularly important for behavioural thermoregulation, and although the pineal complex and melatonin provide a mechanism to process environmental conditions, it seems likely that there also exist other, peripheral sensors. For example, restricted local heating of a dorsal section in a crocodile and a lizard elicited a distinct cardiovascular response (Morgareidge and White 1972; Grigg and Alchin 1976) that must have been independent from direct stimulation of the pineal. Rather, we speculate that peripheral thermal sensors are present in reptiles, and these sensors may be similar to the innervated thermal sensor proteins found in mammals and Drosophila (Patapoutian et al. 2003). Central processing of the peripheral thermal information may involve the NOS NO COX axis that could integrate set-points and cardiovascular control. It is of particular interest that the cardiovascular response to heating and cooling in reptiles is at least in part mediated by the integration between the baroreflex and systemically acting NOS and COX enzymes (Altimiras et al. 1998; Seebacher and Franklin 2003; Seebacher and Franklin 2004a). A link between the local and central functions of COX and NO may connect environmental stimuli to the heart rate hysteresis that is typical of reptilian thermoregulation. Acknowledgments This work was supported by an Australian Research Council Discovery grant to F.S. and C.E.F. References Altimiras J, Franklin CE, Axelsson M (1998) Relationship between blood pressure and heart rate in the salt water crocodile Crocodylus porosus. J Exp Biol 201: Axelrod J (1974) The pineal gland: a neurochemical transducer. 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