Seasonal sympatho-adrenal and metabolic responses to cold in the Alaskan snowshoe hare (Lepus americanus macfarlani)

Comp. Biochem. Physiol., 1975, Vol. 51A,pp. 449 to 455. Pergamon Press. Printed in Great Britain

SEASONAL SYMPATHO-ADRENAL AND METABOLIC RESPONSES TO COLD IN THE ALASKAN SNOWSHOE HARE (LEPUS AMERICANUS MACFARLANI) DALE D. FEISTAND MARIO ROSENMANN Institute of Arctic Biology, University of Alaska, Fairbanks, Alaska 99701, U.S.A. (Received 13 February 1974)

Abstract--1. Winter-acclimatized snowshoe hares achieved a significantly greater maximum metabolic response to cold (Mmnx)than summer hares. 2. Summer hares exposed to + 13°C and winter hares to -20°C excreted similar levels of urinary norepinephrine(NE) and epinephrine (E). 3. Cold exposure of summer hares to -20°C and winter hares to -45°C (conditions which elicit the same metabolic rate in both groups) caused significantly greater NE and E excretion in summer hares. 4. The results suggest that seasonal acclimatization involves enhanced non-shiveringthermogenesis, increased sensitivity to NE and increased Mmax in winter hares which enables retention of a constant annual metabolic range for activity.

INTRODUCTION SEASONAL acclimatization of mammals may involve both insulative and metabolic adjustments for winter survival. Large mammals (e.g. caribou) exhibit primarily insulative changes while small mammals (e.g. mice, rats) are believed to show primarily metabolic compensations (Hart, 1971; Irving, 1972). The snowshoe hare (Lepus americanus) a common mammal in central Alaska and the boreal forest of North America, survives the full impact of the Alaskan winter with a minimum reliance on microclimatic evasion (Morrison, 1964). Previous studies of the metabolism of snowshoe hares in Alaska (Irving et al., 1957) and in Canada (Hart et al., 1965) have shown this lagomorph to be quite resistant to cold. Because the increase in insulative capacity of the white winter pelage (which replaces the brown summer pelage) was found to be comparable to the decrease in thermal conductance of the animal from summer to winter (about 30 per cent change), Hart et al (1965) concluded that seasonal acclimatization in the snowshoe hare is largely insulative. Together with changes in thermal conductance, metabolic changes and enhancement of nonshivering thermogenesis (NST) could also play an essential role in seasonal cold resistance in the snowshoe hare. The findings of Rosenmann & Morrison (1965) of seasonal augmentation of myoglobin in winter suggest that snowshoe hares may undergo substantial seasonal changes in the biochemical capacity of tissues to provide a greater metabolic capability in the winter. No studies of sympatho-adrenal activity or of calorigenic responsiveness to catecholamines (CA) have been reported

for this species. However, several studies of the thermogenic effect of CA in cold-acclimated domestic rabbits (Cottle, 1963; Heroux, 1967; Kockova & Jansky, 1968) suggest only a minor role for CA-stimulated NST in cold-exposed rabbits. The studies reported here began as part of a broader project dealing with ftmetional aspects of snowshoe hares during phases of the 10 year population cycle. Our primary objectives were to determine whether seasonal acclimatization in the hares involved (1) changes in maximum metabolic response to cold (i.e. maximum oxygen consumption) and (2) changes in sympatho-adrenal responses to cold. MATERIALS AND M E T H O D S Animals

Snowshoe hares of both sexes were collected (with wire mesh Tomahawk live traps baited with pelleted rabbit chow) from an area of mixed birch and spruce taiga forest near Fairbanks, Alaska, from June 1971 to June 1973 in November, February, June and August. The animals were housed initially in individual metal cages in an environmental chamber at the prevailing mean ambient seasonal temperature (i.e. - 5 ° C to -10°C in November; -20°C in February; +13°C in June and Augus0 and seasonal photoperiod. They were given Albers rabbit chow and water or snow ad lib. The annual extremes of temperature and light to which hares are normally exposed outdoors in Fairbanks, Alaska, are shown in Fig. 1. Experiments

Two different sets of experiments involving separate hares were usually started on the first day after capture.

449

DALE D. FEIST AND M~.,~io ROSENMANN

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22 Yearly Cycles in Ternperolure ond DrJyllght

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at Fairbanks, Alaska

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Fig. 1. The annual cycle of temperature and light at Fairbanks, Alaska. 1. Metabolic response to cold. In order to determine the metabolic rate of hares during exposure to thermoneutral temperatures and colder, individual hares were transferred from their cages to a metabolic chamber for measurements of oxygen consumption. Additional hares were tested individually in a metabolic chamber for their maximum metabolic response to cold. The body weights of hares used for tests of maximum metabolic response were 1544+ 169 g ( R + S.D.) for summer hares and 1506+ 239 gfor winter hares. 2. Catecholamine excretion response to cold. In order to assess the seasonal sympatho-adrenal activity of hares at the prevailing mean ambient seasonal temperatures and colder, urine was collected each day from hares retained in their original individual cages for estimation of the 24 hr excretion of norepinephrine (NE) and epinephrine (E). Summer hares (June 1972) were exposed initially to + 13°C (mean ambient seasonal temperature) for 7 days and then to - 2 0 ° C for 3 days and - 4 5 ° C for 2 days. Winter hares (February 1972) were exposed to - 2 0 ° C (mean ambient seasonal temperature) initially for 6 days and then to - 4 5 ° C for 3 days. Body weights of hares used for urine collection were 1490+ 129 g on the first day and 1374+ 141 g on the last day for summer hares and were 1594+ 183 g on the first day and 1486+ 178 g on the last day for winter hares. Determination o f metabolic rate

Metabolic rates were determined for hares in summer (June and Augus0 and winter (November and February) by measuring oxygen consumption with a closed circuit automatic manometric respirometer (Morrison, 1951) at thermoneutral temperatures (20°C, 25°C) and below ( - 8 ° C , - 4 0 ° C , -55°C). Low temperatures were achieved by submerging the metabolic chamber in refrigerated glycol or placing it in a Missimer cold chamber. The maximum metabolic response to cold (Mmax) was determined by subjecting the hares to short-term cold stress which exceeded their capability for heat production and resulted in hypothermia. The highest rates of oxygen consumption achieved during periods of 5-10 min were considered Mma x. In general, Mmax occurred during

the first 30 min of cold exposure. The maximum metabolic responses were elicited by two different methods: (1) Winter and summer hares were either shaved (or oiled) and subjected to a helium (80%)-oxygen (20%) atmosphere at temperatures between - 10°C and - 15°C with forced convection from a fan or were left unshaved in helium--oxygen at temperatures between - 4 0 ° C and - 5 7 ° C (Rosenmann & Morrison, 1974). Hypothermic body temperatures as low as 35°C resulted from these exposures. (2) Winter and summer hares were wetted with water of 15°C temperature in an atmosphere of normal air according to the method of Giaja (1925). Final body temperature following 6 0 - 9 0 m i n exposure averaged 26°C (range: 20-35°C). Colonic temperatures were not monitored during the measurements of oxygen consumption but were determined with a thermistor probe inserted to a depth of 8 cm immediately after removal from the metabolic chamber. Urine collection excretion

and determination

o f catecholamine

Urine from each animal was collected daily in a plasticcoated metal pan which contained 1 N HC1 to maintain a pH of about 3. After transfer of the 24 hr urine sample to a plastic container early each morning, the pan was washed with HCI and the washings were added to the urine. Each 24 hr urine sample plus washing was filtered, adjusted to pH 3 and frozen until subsequent processing. At the time of analysis, catecholamines were isolated by the aluminum oxide adsorption method and assayed fluorometrically (van Euler & Lishajko, 1961). Recovery studies showed a mean recovery of 70 per cent for N E and 64 per cent for E. Values given for N E and E represent the free amines but are not corrected for losses during isolation. Unless otherwise stated, values are expressed as the m e a n + S.E. On the basis of previous studies on laboratory animals and man the N E and E excreted appears to be directly proportional to the quantity released at sympathetic nerve endings and adrenal medullary cells (Wurtman, 1965; Iversen, 1967).

Seasonal responses to cold in the snowshoe hare Hence, CA excretion provides an index of the general level of activity of the sympatho-adrenal system. Although it remains to be further verified, it is assumed here that this relationship applies in snowshoe hares.

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Statistical analysis

The statistical significance of the difference between mean values was determined by the Student t-test (Simpson et al., 1960).

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RESULTS M a x i m a l metabolic rates

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As shown in Fig. 2, winter hares were able to achieve higher Mmax than summer hares. Winter hares achieved a maximum metabolic rate 8"0 times their standard metabolic rate. This increase was significantly greater ( P < 0.01) than that of 6-4 times the standard rate shown by the summer hares. Mm~x values elicited by the two different methods were similar (i.e. not significantly different) within each seasonal group. Snowshoe Hore Mox. Melabolic Response to Cold

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Fig. 3. Seasonal changes in the metabolic response of snowshoe hares to cold. Curves for summer* and winter* were derived from Hart et aL (1965). Values plotted from the present study** represent the mean and vertical range. The temperature for maximum metabolic response (Mr~ x) is given below the arrow as the mean+S.E. tance of the winter hares was about 33 per cent lower than in the summer hares. If we assume the validity of extrapolation of these curves to very low temperatures then summer hares would reach maximum metabolic rates of 3-41+0.15 cm a O~/g. hr at air temperatures between - 68°C and - 80°C. Winter hares could tolerate much lower air temperatures before reaching maximal rates of 4.17+0"23cm 3 O2/g. hr at about - 145°C to - 170°C.

I

Summer

Fig. 2. Seasonal differences in the maximum metabolic response to cold (Mmax) in snowshoe hares. Mean + S.D. indicated by diamonds; S.E. and range by horizontal and vertical lines respectively. The mean winter value for Mmsx/MBt was significantly greater (P<0.01) than the summer value. Met = 3"8 cms O2(g-3"z7 . hr) -t. The number within the diamond is the number of animals tested. The difference in the metabolic capacity of summer and winter hares in response to cold was even more apparen{ upon extrapolation of these rates (in helium-oxygen or during wetting) to the effective air temperatures which would elicit the mean maximum metabolic rates. Figure 3 shows a comparison of oxygen consumption of summer and winter hares at different ambient temperatures. The regression lines were derived from the data of Hart et al. (1965) for Canadian hares. Our data for Alaskan hares subjected to air temperatures from 25 to - 5 7 ° C fit these lines well (Fig. 3). There was no apparent difference in the resting metabolic rates of summer and winter hares at thermoneutral temperatures. Below thermoneutrality the metabolic rates of winter hares were lower than those of summer hares at all temperatures indicating that the thermal conduc-

Catecholamine excretion

As shown in Fig. 4, summer hares kept at + 13°C (and 9.5°C) excreted the same levels of urinary catecholamines (2.18 + 0.19 Fg NE/kg per 24 hr; 1.14 + 0" 11/zg E/kg per 24 hr) as did winter hares exposed to - 2 0 ° C (2.88+0.25/~g NE/kg per 2 4 h r ; 1.42+ 0.29 Fg E/kg per 24 hr). Data not shown in Fig. 4 for hares studied in November and August gave similar results. Two hares caught in November and exposed to - 5 ° C excreted 2.37/xg NE/kg per 24 hr while eight hares caught in August and exposed to + 12°C for a week excreted 3.73 + 0.32 #g NE/kg per 24 hr and 1.53 + 0.18 Fg E/kg per 24 hr. Thus hares exposed to temperatures normally experienced in summer and winter show similar levels of sympathoadrenal activity. As shown in Fig. 4, when exposed to - 2 0 ° C summer hares increased NE excretion about sixfold ( P < 0.001) in the first 24 hr and eightfold in the next 24 hr. They increased E excretion about threefold (P<0.05) in the first day, sixfold on the second day and 7.5 fold (P<0.01) on the third day (Fig. 4). Subsequent exposure of summer hares to - 45°C did not significantly alter the increased NE and E responses. When winter hares were exposed to - 4 5 ° C they showed only a threefold (P<0.07)

DALE D. FEm'r AND MARIO ROSENMANN

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Fig. 4. Seasonal differences in catecholamine excretion response to cold in snowshoe hares. Values represent the mean + S.E. The period of exposure to + 9-5°C was due to a temporary malfunction in the temperature regulator of the environmental chamber. increase in NE excretion after 2 days and no significant increase in E. As indicated in Fig. 3, summer hares at - 20°C and winter hares at - 45°C would be expected to exhibit the same metabolic rate of 1.8 cm 3 O2/g per hr. But as shown in Fig. 4, the catecholamine excretion responses in the different seasonal groups at this same metabolic rate are quite different. At - 2 0 ° C , summer hares show a strong activation of both the sympathetic nervous system (release of NE) and adrenal medulla (release of E). At - 4 5 ° C , winter hares show only a more moderate activation of the sympathetic nervous system. DISCUSSION

The present findings suggest that seasonal acclimatization in Alaskan snowshoe hares involves not only insulative changes which reduce the thermal conductance but also metabolic adjustments which are reflected in a greater maximum metabolic capacity and an altered sympatho-adrenal response to cold in the winter.

Changes in maximal metabolic responses to cold The seasonal changes in M,~x reported here for snowshoe hares in the cold resemble the responses found in several species of small mammals after cold acclimation in the laboratory. These previous studies on small mammals indicate that the gmax, as elicited by cold, is considerably influenced by the previous thermal history (Hart, 1971). For example

(Table 1), mice and rats exposed to constant cold (e.g. 6°C) in the laboratory for several weeks show a greater Mmax than those acclimated to a therrnoneutral temperature (Hart & Jansky, 1963 ; Gelineo, 1964; Pasquis et al., 1970). With the exception of work on muskrats (Hart, 1962), no other study seems to have been published on maximum metabolic rates in seasonally acclimatized adult mammals. Hart (1962) tested the metabolic rates of summer and winter muskrats at various air temperatures down to - 6 5 ° C for about 1 hr. He reported (Table 1) a similar Mmax in both summer and winter groups and suggested "no appreciable seasonal changes". However, his data suggests that winter muskrats were able to sustain M t ~ x at lower air temperatures (below - 40°C) and resist hypothermia better at low temperatures than were summer muskrats. Previous studies of the metabolism of snowshoe hares (Irving et al., 1957; Hart et al., 1965) have not considered maximum metabolic responses to cold. The domestic rabbit (Table 1) has been reported to have a metabolic rate during acute cold exposure and exercise of 3.5 times the resting value (Hart & Heroux, 1955). But no data on Mmax in coldacclimated rabbits have been published. Thus, summer snowshoe hares exhibit a ratio of Mmax to standard metabolism ( M ~ comparable to that reported for other species of smaller or similar size. However, winter hares seem to have a greater Mmax/MBt value than reported for cold-acclimated mice and rats and winter-acclimatized muskrats (Table 1). Changes in shivering and/or non-shivering thermogenesis (NST) must account for the enhanced metabolic capacity of the winter-acclimatized snowshoe hares. Hart et al. (1965) made electromyographic measurements from the back region of summer- and winter-acclimatized snowshoe hares exposed to cold. They found that shivering in the cold at any given temperature (down to - 4 0 ° C ) was greater in the summer hare, that shivering was greater in the summer hare than the winter hare at the same oxygen consumption and that shivering reached a maximum at - 10°C in summer hares and at - 20°C in winter hares and remained at a constant level down to at least - 4 0 ° C . The maximum level of shivering in winter hares appeared to be about 40 per cent lower than in summer hares. We did not measure shivering in our hares during cold exposure but presumably shivering in response to cold of hares in this study was similar to that observed by Hart et al, 1965. Our subjective impressions from visual observations during the metabolic experiments tend to support this conclusion. Both summer and winter hares shivered intensively during normothermia prior to, and at Mmax. Shivering was also observed during early hypothermia. Although summer hares exposed to - 2 0 ° C and winter hares exposed to - 4 5 ° C would be expected

Seasonal responses to cold in the snowshoe hare

453

Table 1. Comparison of maximum oxygen consumption in the snowshoe hare and other mammals Species

Weight (g)

Condition

Maximum (cm 3 0 ~ / g . hr)

Max/min*

Max]std.t

9.3 10.5

---

6.3 7-0

Pasquis et aL (1970)

Reference

Mouse (albino) Mus rausculus

33

30°C acclimated 6°C acclimated

Rats Rattus rattus

--

30-32°C acclimated 16-20°C acclimated 0-2°C acclimated 30°C acclimated 6°C acclimated 30°C acclimated 6°C acclimated

-----4.9~: 5.4

2-7 3.6 3.4 2.5 4-0 3.1 3.4

-----6.4 7.0

Gelineo (1964)

1100

Summer and winter

3-5

3.5

6"0

Hart (1962)

1544 1506

Summer Winter

3.4 4"2

4.5 5"6

6-4 8"0

Present study

2.8

3.5

6.0

Hart & Heroux (1955)

R. rattus

-

R. norwegicus

Muskrat Ondatra zibetheca Snowshoe hare Lepus americanus Rabbit (domestic) Oryctolagus cuniculus

-

375

2500

Hart & Jansky (1963) Pasquis et al. (1970)

* Minimum metabolism while resting at thermoneutral temperature. t Standard Metabolism = 3.8 cm a O2(g -°'2~ . hr) -1. Maximum rate estimated during exercise and rest at low temperature (i.e. 6 to - 10°C). Table 2. Seasonal differences in metabolism, shivering and catecholamine excretion in snowshoe hares exposed to cold Catecholamine excretions (/~g/kg. 24 hr) Acclimatization Group Summer Winter

Temperature (°C)

Metabolism* (cm a O2/g. hr)

+ 13°C -20°C - 20°C -45°C

0-75 1-8 (2-4x)§ 1"2 1.8 (1.5x)

Shiveringt 0 4.5 2'7 2'7

NE 2-18 17.20 ( S x ) § 2.87 7.88 (2.8x)

E 1.14 8-52 (7.5 x ) 1.42 2.63 (1.9x)

* Values for metabolic rate are based on the relationship shown in Fig. 3. t Shivering is expressed in arbitrary units based on data of Hart et al. (1965) for muscle electrical activity in hares at various temperatures. Levels for summer hares at + 13°C (and +9-5°C) and winter hares at - 2 0 ° C represent means of values for all days of exposure to these temperatures; levels for summer hares at - 20°C and winter hares at - 45°C represent the maximum value achieved during exposure to these temperatures. § Brackets contain the factor of increase in the level of metabolism or of N E or E after exposure to cold stress. to exhibit the s a m e m e t a b o l i c rate (Table 2), t h e winter h a r e s would be expected to exhibit 40 p e r cent less shivering t h a n the s u m m e r hares ( H a r t et al., 1965). I f these differences in shivering a p p l y to hares in the present s t u d y a n d if the rate o f oxygen cons u m e d p e r u n i t o f shivering is c o m p a r a b l e for b o t h seasonal groups, it seems quite clear t h a t the winter hares utilize m o r e N S T t h a n the s u m m e r h a r e s to achieve the same m e t a b o l i c rate. T h e m e c h a n i s m s for the p r o b a b l e increase in N S T a n d greater m e t a b o l i c r e s p o n s e to cold in the winter

h a r e m u s t involve b i o c h e m i c a l a n d / o r physiological a d j u s t m e n t s w h i c h e n h a n c e the capacity of m e t a b o l i c p a t h w a y s liberating h e a t a n d / o r the supply o f s u b s t r a t e a n d oxygen in t h e r m o g e n i c tissues (Alexander, 1962; Chaffee & Roberts, 1971 ; Jansky, 1973). I n cold-acclimated mice a n d rats a n d in some acclimatized small m a m m a l s , e n h a n c e d N S T m a y be a c c o u n t e d for in p a r t b y the increased t h e r m o g e n i c capacity o f b r o w n fat ( D i d o w & H a y w a r d , 1969; S m i t h & Horwitz, 1969). However, b r o w n fat does n o t seem to b e involved in

454

DAL~ D. FEASTAND MARIOROSEN~/a~NN

thermogenesis or seasonal aclimatization in adult snowshoe hares since, during the course of many autopsies of adult hares from all seasons of the past several years, we have found no brown fat (Feist, unpublished observations). The underlying mechanisms for the increased metabolic capacity of the winter hare remain to be resolved. The adaptive value of an increased Mmax in the winter may appear to be of little significance since the maximal rates for both summer and winter hares would be elicited at temperatures well below those normally experienced. But the greater metabolic capacity in the winter hare would be important for allowing longer or more strenuous periods of activity (e.g. foraging or escaping a predator) during exposure to extreme cold. F o r example, comparison of the metabolic capability of summer and winter hares to expend energy for activity above that required for thermoregnlation (i.e. metabolic range for activity = Mmax-Mr~t; where Mr~ t = the resting metabolic rate at a given temperature, Hart & Jansky, 1963) indicates that the winter hare at 30°C (mean low ambient temperature in January) and the summer hare at + 10°C (mean low ambient temperature for July) have the same metabolic range for activity (e.g. Mmax-Mrea: summer range at +10°C is 3 . 4 - 0 . 8 = 2 . 6 c m S O z / g . h r ; winter range at - 3 0 ° C is 4-2-1.5 = 2.7 cm 3 O2/g. hr). Thus, the increased Minx in winter ensures the retention of a constant metabolic range for activity throughout the year. -

Sympatho-adrenal response to coM The level of NE excreted by summer hares at a thermoneutral temperature of + 13°C (Fig. 4) was comparable to values reported previously for the rat (Leduc, 1961) and hamster (Feist, 1972) exposed to 22°C. However, the level of E excreted by these hares was three- to fourfold higher than reported for rats and hamsters. This may indicate a greater importance of adrenal medullary release of E in daily resting metabolism of the snowshoe hare than in the smaller rodents. In conjunction with the higher excretion of E, a greater percentage of E (95-100 per cent of total CA; Feist, unpublished data) was found in the adrenal gland of the snowshoe hare than has been reported for rats and hampsters (75-80 per cent of total CA; Leduc, 1961 ; Feist, 1972). The dramatic increase in NE and E excretion in summer hares during exposure to - 2 0 ° C (Fig. 4) suggests that this cold stress elicited an increased release of NE from sympathetic nerve endings and E from adrenal medullary cells to support increased NST. A similar catecholamine (CA) excretion response has been observed in various warmacclimated mammalian species such as rats (Leduc, 1961) and hamsters (Feist, 1972) exposed to milder cold stress (e.g. 5°C). It has also been shown that in

these and certain other small mammals thermogenesis mediated by N E (and to some extent by E) is the most important mechanism of NST (Jansky, 1973). The rapid rise in N E on the first day and the slower rise in E to a peak after 3 days supports the idea that N E mediation of NST in the hares was more important in the initial response to cold stress than E. Under these conditions E was probably acting as a secondary mediator o f N S T (Leduc, 1961) and as a vasodilator for skeletal muscle blood vessels (von Euler, 1967) since shivering was increased considerably (Table 2). Further tests of CA excretion and sensitivity to CA at temperatures normally experienced by hares below thermoneutrality are needed to clarify the importance of CAmediated NST in the summer hare. The results of several studies of the calorigenic response of domestic rabbits during warm and cold acclimation in the laboratory suggest that metabolic acclimation involving CA-stimulated NST may not develop to the same degree as seen in smaller mammalian species (Cottle, 1963; Heroux, 1967; Kockova & Jansky, 1968). However, data on domestic rabbits may not apply to snowshoe hares for at least two reasons. First, rabbits are about twice the size of an adult snowshoe hare and Heldemaier (1971) has demonstrated an inverse relationship between body size and capacity for NE-mediated NST. Second, the acclimation temperatures for most of the experiments in both warm (e.g. 25°C) and cold (e.g. 6°C) were well above the comparable ambient temperatures normally experienced during acclimatization of snowshoe hares in the field. The fact that the sympatho-adrenal response in winter hares at - 2 0 ° C is the same as in summer hares at +13°C and considerably lower than in summer hares at - 2 0 ° C suggests that increased insulation with a reduction of thermal conductance enables the winter hare to resist - 2 0 ° C without increased CA-mediated NST. However, as pointed out above, comparison of the metabolic rate, the expected shivering response and the CA excretion response of winter hares exposed to - 4 5 ° C and summer hares exposed to - 2 0 ° C (Table 2) indicates an increased metabolic component of seasonal acclimatization to cold. If shivering thermogenesis is 40 per cent lower in the winter hare than in the summer hare at the same metabolic rate, then NST must be increased in the winter hare. It seems reasonable to assume that the several-fold increase in urinary NE in the winter hare reflects sympathetic stimulation of at least part of this NST. Furthermore, the significantly lower C A excretion response in the winter hare to support more NST suggests an increase in sensitivity of thermogenic tissues to stimulation by NE.

Acknowledgements--We would like to express our appreciation to Dr. Robert G. White for critical reading of the manuscript and for helpful suggestions; to Marilyn

Seasonal responses to cold in the snowshoe hare Ailes and David Wilson for competent technical assistance; and to the National Institutes of Health and National Science Foundation for financial support under NIH Grant GM 10402 and NSF Grant 36369. REFERENCES

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Key Word Index--Seasonal acclimatization; coldexposure; sympathoadrenal activity; catecholamines; norepinephrine; epinephrine; non-shivering thermogenesis; maximum metabolism; snowshoe hare; Lepus americanus.