Norepinephrine Turnover In Heart Research Articles

Long-term exposure to ozone alters peripheral and central catecholamine activity in rats.

In addition to its noxious influence on lung airways, ozone inhalation can induce extrapulmonary neural dysfunctions the mechanisms of which are poorly understood. This study was intended to characterize the effects of long-term exposure to ozone (0.5 ppm, 5 days) on catecholamine activity in rat sympathetic efferents and brain areas of prime importance to adaptation to environmental stressors. Catecholamine activity was assessed by estimating the turnover rate of catecholamines and in vivo tyrosine hydroxylase activity in peripheral and central structures, i.e., heart, lungs, superior cervical ganglia, cerebral cortex, hypothalamus and striatum, A2 cell group within the nucleus tractus solitarius (NTS), and locus ceruleus (A6). Ozone inhibited norepinephrine turnover in heart (-48% of the control level) but not in lungs. Ozone failed to modify the tyrosine hydroxylase activity in superior cervical ganglia, and the catecholamine content in the adrenal glands. In the central nervous system, ozone inhibited tyrosine hydroxylase activity in noradrenergic brainstem cell groups, including the locus ceruleus (-62%) and the caudal A2 subset (-57%). Catecholamine turnover was decreased by ozone in the cortex (-49%) and striatum (-18%) but not in the hypothalamus. The data show that ozone can produce marked neural disturbances in structures involved in the integration of chemosensory inputs, arousal, and motor control.

Does enhanced sympathetic tone contribute to angiotensin II hypertension in rats?

To determine whether enhanced sympathetic tone contributes to the maintenance of chronic angiotensin II (A II, 10 ng/min i.v. for 10 days) hypertension in rats, sympathetic activity was assessed in hypertensive and control rats by measuring norepinephrine (NE) turnover (α-methyl-p-tyrosine) in peripheral organs and by measuring depressor responses to ganglionic blockade in conscious rats. Pressor responses to methoxamine (1–8 μg/min) and arginine vasopressin (0.5–4 ng/min) were also obtained in rats with ganglionic blockade. Chronic A II infusion produced significant hypertension (mean±S.E. tail cuff pressure: 176±5 vs. 134±2 mm Hg in controls; n=23 each group) but there were no significant differences in NE turnover in heart, kidney, skeletal muscle, or intestine in hypertensive rats compared with controls. Ganglionic blockade produced a significantly larger decrease in mean arterial pressure in A II-treated rats when compared with controls (73±7 vs. 38±2 mm Hg, n=18 for each group). Dose-response curves for methoxamine and vasopressin were not significantly different between groups. The results suggest that the maintenance of chronic A II hypertension does not involve postsynaptic interactions between A II and the sympathetic system. The NE turnover data do not support the hypothesis that rats with chronic A II hypertension have enhanced sympathetic tone.

Effects of Iron Repletion and Correction of Anemia on Norepinephrine Turnover and Thyroid Metabolism in Iron Deficiency

The reversibility of the alterations in norepinephrine (NE) content and turnover in interscapular brown adipose tissue and heart of iron-deficient rats has not been demonstrated. We therefore examined NE metabolism in age-matched male Sprague-Dawley rats depleted of iron by dietary means and after repletion with iron dextran. Heart NE content was 58, 61, and 85% of controls at 0, 3, and 7 days after repletion, whereas interscapular brown adipose tissue-NE content was 87, 103, and 104% of controls. Fractional heart NE turnover was 225% greater in iron-deficient anemics than controls but normalized within 3 days. Interscapular brown adipose tissue NE turnover was 58%, 46%, and 20% above controls in iron-deficient rats after 0, 3, or 7 days of iron repletion. Hematocrit returned to 80% of normal in 7 days. Liver triiodothyronine production also increased to 80% of control in this period. A second experiment used isovolemic exchange transfusion to examine the influence of anemia per se on these alterations in organ NE turnover. Acute correction of anemia in iron deficiency did not alter brown fat NE turnover. Heart NE turnover was significantly lower in anemic animals regardless of iron status. Defects in heart and brown fat NE metabolism are reversible within 7 days of iron treatment as are alterations in triiodothyronine production. Anemia per se has little effect on brown fat NE metabolism but does dramatically decrease heart NE content.

Norepinephrine turnover in iron deficiency: Effect of two semi-purified diets

The effects of two dietary treatments on norepinephrine turnover in iron deficiency were examined. These studies were designed to bridge the gap between previous studies of poor thermoregulation in iron deficiency which used a diet (HMW, Hubbel-Mendel-Wakeman formulation) relatively high in fat (46% of calories) and moderate in carbohydrate (46% of calories) and the more recent studies of thermogenesis in iron deficiency which use the AIN-76 recommended diet which is relatively low in fat (11% of calories) and high in carbohydrate (67% of calories). Iron deficient rats grew less well and had depressed thyroid hormone concentrations regardless of dietary treatment group. The HMW diet significantly increased norepinephrine turnover in heart in iron deficient animals relative to AIN diet but had no effect in controls. Brown adipose tissue norepinephrine turnover was threefold higher in HMW rats fed a low iron diet, and only 67 percent higher in control rats. This study demonstrates that certain modest macronutrient manipulations affect norepinephrine content and turnover more in iron deficient than controls. However, abnormalities in thyroid hormone concentrations persist in iron deficient animals regardless of these dietary treatments.

Sympathetic nervous system responses to cold exposure and diet in rat skeletal muscle.

Norepinephrine (NE) turnover measured in individual skeletal muscles of the rat assessed sympathetic responses to cold (4 degrees C) and diet. Acute cold exposure increased NE turnover slightly (15-50%) in all muscles examined, including gastrocnemius, tibialis anterior, tensor fascia lata, and soleus, in contrast, cold-accelerated NE turnover in heart by one- to twofold and in interscapular brown adipose tissue (IBAT) by more than threefold. Similar results in skeletal muscle and heart were obtained after 1 wk of cold exposure. Examination of dietary effects on NE turnover, comparing rats fed a sucrose-supplemented diet for 3 days with those fasted for 2 days, indicated that sympathetic activity in skeletal muscle was unresponsive to dietary intake. In heart and IBAT, on the other hand, NE turnover in sucrose-fed rats was twice that obtained in fasted animals. Taken together, the lesser effect of cold and the undetectable response to diet indicate that sympathetic outflow to skeletal muscle is regulated differently than that to heart or IBAT and imply that skeletal muscle is not a major site for sympathetically mediated thermogenic responses to cold exposure or to dietary alteration, such as fasting and sucrose feeding.

Cardiac sympathetic activity during rat pregnancy

The turnover of injected tracer [ 3H] norepinephrine (NE) was determined in heart and interscapular brown adipose tissue of virgin and 10-day and 20-day pregnant rats. In two experiments fractional [ 3H]NE turnover in heart was 87% and 92% higher in 20-day pregnant animals compared to virgin controls, but did not differ between 10-day pregnant and control animals. NE turnover in brown adipose tissue did not differ between control and pregnant animals at either gestational age. Twenty-four-hour urinary excretion of NE, epinephrine (E), and dopamine (D) was measured serially in six pregnant rats and compared to virgin controls. NE excretion during pregnancy was significantly higher than the controls and showed a progressive increase during the last third of pregnancy. At term the excretion rate was 2.6-fold greater than that of controls. Excretion of E and D did not differ between pregnant and nonpregnant animals. It is concluded that cardiac sympathetic nervous system activity increases during rat pregnancy. That this change in sympathetic activity is not global is indicated by the finding of unchanged NE turnover in interscapular brown adipose tissue. Urinary excretion data are consistent with increased sympathetic activity during late gestation, with no change in adrenal medullary function.

Effect of experimental hyperinsulinemia on sympathetic nervous system activity in the rat

Since insulin acutely stimulates the sympathetic nervous system, a role for sympathetic overactivity has been hypothesized to underlie the association between chronic hyperinsulinemia and hypertension. To assess the effect of sustained hyperinsulinemia on sympathetic function, [3H]norepinephrine (NE) turnover was measured in rats injected with insulin for 14d. NE turnover in insulin-treated animals given free access to lab chow and a 10% sucrose solution was compared with that obtained in rats fed chow alone or chow plus sucrose. Sucrose ingestion increased NE turnover in heart, brown adipose tissue, and liver, but exogenous insulin did not augment turnover beyond that seen in animals given sucrose alone. This study, therefore, provides no evidence that chronic hyperinsulinemia, sufficient to induce peripheral insulin resistance, stimulates sympathetic activity more than that produced by chronic sucrose ingestion.

Reduced norepinephrine turnover in interscapular brown adipose tissue of obese rats after ovariectomy

Norepinephrine (NE) turnover, which is a reliable indicator of sympathetic nervous system (SNS) activity, was measured in the interscapular brown adipose tissue (IBAT), heart, and pancreas of ovariectomized (OVX), sham-operated rats receiving injections of estradiol benzoate (EB). Ovariectomized rats (OVX rats) ate much more than controls and became obese, whereas the administration of EB to obese OVX rats decreased their food intake to the level below that of sham-operated animals and body weight to the level of sham controls. The results from studies using the inhibition of NE biosynthesis with α-methyl-p-tyrosine or radiolabeled NE to measure NE turnover significantly demonstrated reductions in SNS activity in IBAT of OVX rats than in sham controls, whereas the injections of EB to OVX rats significantly restored the decrease of NE turnover in IBAT. NE turnover in heart and pancreas were similar in these three groups. It is suggested that reduced NE turnover in IBAT may be a major factor in the development of obesity after ovariectomy (OVX).

Effect of glucose and fat feeding on norepinephrine turnover in rats.

The norepinephrine turnover in organs of glucose-fed and fat-fed rats were compared to those of starved rats. Rats fed only glucose had higher rates of norepinephrine turnover than starved rats in heart, pancreas, kidney, liver, and lung. The effect of glucose-feeding on norepinephrine turnover was most pronounced in heart (+197%) and pancreas (+120%), which were examined in the fat feeding study. Rats fed only fat showed the same suppression of insulin levels as fasting rats, and a greater reduction in plasma glucose levels. However, their norepinephrine turnover in heart (+182%) and pancreas (+173%) was similar to that of glucose-fed rats. Thus glucose and fat increase norepinephrine turnover in the absence of any other nutrients. If these nutrients increase norepinephrine turnover via the same intermediate signal, it cannot be insulin or increased glucose metabolism.

Hypothalamic obesity, brown adipose tissue, and sympathoadrenal activity in rats.

Obesity-producing, hypothalamic knife cuts and ventromedial hypothalamic (VMH) lesions in ad libitum-fed adult rats increased intake of a high-fat diet (123 and 130%) and energy retention (880 and 1,099%) during the 4-wk period postsurgery; even when pair fed to control rats, energy retention of the knife-cut and lesioned rats was still elevated (105 and 155%). Thermogenic capacity of brown adipose tissue (BAT), estimated from guanosine diphosphate (GDP) binding to BAT mitochondria, was unchanged in hyperphagic knife-cut and VMH-lesioned rats and was reduced approximately 50% when these rats were pair fed to controls. Urinary excretion of norepinephrine (NE) was approximately twofold higher in ad libitum-fed, knife-cut, and lesioned rats than in control rats; restriction of energy intake decreased NE excretion to control values. Rates of NE turnover in heart paralleled urinary NE excretion, whereas NE turnover in BAT was generally not increased in the hyperphagic rats. Urinary epinephrine excretion, an index of adrenal medullary activity, was depressed in all knife-cut and VMH-lesioned rats. Hyperphagia coupled with a lack of increased heat production in BAT causes gross obesity in ad libitum-fed, knife-cut, and VMH-lesioned rats, whereas obesity in pair-fed rats develops in part at least as a result of reduced heat production by BAT.

Effects of Diet on Norepinephrine Turnover in Obese (ob/ob) Mice

Effects of energy restriction and of supplemental sucrose or fat on norepinephrine (NE) turnover in brown adipose tissue (BAT) and heart of female obese (ob/ob) and lean mice were examined. Rates of NE turnover in BAT of control female obese mice (8 weeks old) were 39% lower than in control lean mice; no differences were evident in hearts of these mice. Energy intake of 6-week-old ob/ob mice was restricted to the intake of lean mice for 2 weeks. This restriction decreased intake by 41% and reduced rates of NE turnover in heart (-15%), but not in BAT, of obese mice. Next, 7½-week-old lean and obese mice were given access to stock diet and a 30% sucrose solution for 3–4 days. Intake of stock diet decreased by more than 50%. Total energy intake increased in lean mice (+18%), but decreased (-19%) in obese mice. When a 10% sucrose solution was offered intake of stock diet still decreased, but total energy intake was unchanged in lean and obese mice. Oxygen consumption increased in lean mice (+19 to +24%), but not in obese mice, when fed either 30 or 10% sucrose solutions, or a fat-supplemented diet where fat isocalorically replaced the sucrose consumed from 30% sucrose solution. Rates of NE turnover were not significantly increased in lean mice fed the 30% sucrose solution, but were increased in BAT (+34%) and heart (+25%) in lean mice fed the fat-supplemented diet. In obese mice rates of NE turnover were increased in BAT (+40%) and heart (+33 to +47%) when fed either the 30% sucrose solution or the fat-supplemented diet. Thus, obese mice failed to exhibit dietary-induced thermogenesis even though the dietary manipulation increased rates of NE turnover in their BAT. Possibly BAT of obese mice is refractory to NE in short-term feeding trials.

Effects of thyroxine on Na +, K +-ATPase and norepinephrine turnover in brown adipose tissue of obese ( [formula omitted]) mice

Thyroxine treatment improves some of the defective thermogenic properties of obese ( ob ob ) mice. Because brown adipose tissue (BAT) is an important thermogenic organ in mice, effects of thyroxine treatment on Na +, K +-ATPase, a thyroid-hormone responsive enzyme, and on rates of norepinephrine (NE) turnover, an indicator of sympathetic nervous system activity, in BAT of lean and obese mice were evaluated. Female mice, six weeks old, were injected with approximately 4 μg thyroxine daily for 2 weeks. Numbers of Na +, K +-ATPase enzyme units in BAT were similar in control lean and obese mice. Thyroxine treatment increased numbers of Na +, K +-ATPase enzyme units by 60% and 100% in lean and obese mice, respectively, indicating that the BAT of obese mice was responsive to thyroxine treatment. Fractional rates of NE turnover were 75% faster in BAT of control lean mice than in obese mice. Thyroxine treatment decreased functional rates of NE turnover in BAT of lean mice by 35%, but had no effect on NE turnover in BAT of obese mice. Rates of NE turnover in heart and pancreas of control lean and obese mice were unaffected by phenotype. Although the decreases in fractional rates of NE turnover in heart (−23%) and pancreas (−11%) of lean mice in response to thyroxine injections were not statistically significant, the calculated rates of NE turnover (fractional rate of NE turnover times the NE content of the organ) in these organs of lean mice were decreased 25% to 30% ( P < 0.05) in response to thyroxine. Thyroxine injections did not affect NE turnover in either heart or pancreas of obese mice. Thus, in each organ of lean mice examined, thyroxine treatment decreased calculated rates of NE turnover, whereas NE turnover in obese mice was unaffected by thyroxine treatment. Possibly thyroxine treatment had a differential effect on metabolic events post NE release in lean and obese mice.

Effects of dietary carbohydrate, fat, and protein on norepinephrine turnover in rats

To investigate effects of diet composition on rates of norepinephrine (NE) turnover in sympathetically innervated organs, weanling rats were fed for 2 to 2 1 2 weeks diets varying in carbohydrate (74.2% to 7.4% of total metabolizable energy) and fat (5.2% to 72.0%), or diets varying in protein (9.9% to 39.6%) and carbohydrate (77.8% to 48.1%). Changing the proportions of carbohydrate and fat in the diet, while maintaining similar intakes of energy and all other essential nutrients did not affect rates of NE turnover in heart, white adipose tissue (WAT), liver or pancreas and only minimally affected NE turnover in interscapular brown adipose tissue (IBAT). Decreasing the proportion of protein in the diet from 39.6% to 9.9% accelerated rats of NE turnover in heart (52%), IBAT (20%), WAT (42%), and liver (37%). When rats fed a diet containing 19.8% protein were also given a 10% (wt/vol) sucrose solution to drink for three days, their rates of NE turnover increased in heart (45%), IBAT (17%), liver (71%), and pancreas (55%). This response to sucrose depended on the protein content of the diet, since rats fed a 9.9% protein diet in which rates of NE turnover was already accelerated had no further increase in NE turnover when given the sucrose solution to drink. These data demonstrate that diet composition can affect activity of the sympathetic nervous system, as indicated by changes in rates of NE turnover. Changing the proportion of protein in the diet was more effective in altering NE turnover than changing the proportion of carbohydrate or fat.

Increased sympathetic nervous system activity in rat spleen and heart following vitamin A depletion.

The effect of vitamin A depletion on the functional state of the sympathetic nervous system (SNS) was evaluated in rats. Urinary excretion of norepinephrine (NE) and epinephrine (E) significantly increased in the vitamin A-depleted rats. Vitamin A depletion caused a significant increase in NE turnover in heart and spleen, which was determined from the rate of fall in NE content in these tissues after blockade of NE biosynthesis. In rats rendered vitamin A depleted there was a loss in the number of beta-adrenergic receptors in the spleen with a concomitant decrease in the apparent KD for the receptors. These changes in beta-adrenoceptors were prevented by administration of quinacrine, a phospholipase A2 inhibitor. The effects of quinacrine on such changes indicate that phospholipids may be involved in modulating the changes in the number of receptors and their affinity to the ligand. This study suggests that the SNS in rat spleen and heart are stimulated following vitamin A depletion.

Dopamine accumulation after dopamine β-hydroxylase inhibition in rat heart as an index of norepinephrine turnover

Dopamine concentration in rat heart is normally very low, only a few percent of the concentration of norepinephrine. After treatment of rats with a dopamine β-hydroxylase inhibitor, l-cyclohexyl-2-mercapto-imidazole (CHMI), there was a rapid increase in dopamine concentration even before norepinephrine concentration had decreased perceptibly. This accumulation of dopamine was readily measured by liquid chromatography with electrochemical detection. Since the percentage change in dopamine was much greater than the percentage change in norepinephrine, especially at early times, measurement of dopamine accumulation rather than norepinephrine decline was considered as a useful measure of norepinephrine turnover. Drugs that act on noradrenergic receptors and are known to alter norepinephrine turnover were found to alter the rate of dopamine accumulation. Clonidine and guanabenz decreased dopamine accumulation after CHMI, whereas piperoxan (but not prazosin) increased dopamine accumulation after CHMI. Pergolide, a dopamine agonist whose lowering of blood pressure and cardiac rate has been suggested to be due to suppression of neurogenic release of norepinephrine, also decreased dopamine accumulation after CHMI. The results suggest that measuring dopamine accumulation may have advantages over measuring norepinephrine disappearance after dopamine β-hydroxylase inhibition as an indicator of norepinephrine turnover in heart.

Effect of diet and cold exposure on norepinephrine turnover in brown adipose tissue of the rat.

Brown adipose tissue (BAT) is an important site of adaptive changes in thermogenesis in the rat. The sympathetic nervous system, which richly supplies BAT, is thought to play an important role in the regulation of BAT thermogenesis because catecholamines stimulate and beta adrenergic blocking agents inhibit oxygen consumption in this tissue. The present studies were carried out to assess directly sympathetic activity in BAT in response to cold exposure and to changes in dietary intake, both of which alter heat production in the rat. Sympathetic activity was determined from the rate of norepinephrine (NE) turnover in interscapular brown adipose tissue (IBAT) after preliminary experiments validated the use of NE turnover techniques in IBAT. Acute exposure to 4 degrees C increased NE turnover in IBAT 4- to 12-fold compared with ambient temperature controls, depending upon the interval over which the turnover measurement was made, while in the heart NE turnover doubled in response to the same cold stimulus. In animals exposed to cold continuously for 10 d before study, NE turnover measurements in IBAT and in the heart were elevated comparably to those obtained during acute exposure. Alterations in feeding were also associated with changes in NE turnover in IBAT. Fasting for 2 d decreased NE turnover in IBAT (-35% from 29.2+/-4.2 ng NE/h to 18.9+/-5.9) and in heart (-52%). In animals fed a "cafeteria" diet, a model of voluntary overfeeding in the rat, NE turnover was increased in both IBAT (+108% from 24.8+/-4.5 ng NE/h to 51.7+/-6.8) and heart (+66%). Because ganglionic blockade exerted a greater effect on NE turnover in IBAT in cafeteria-fed rats than in controls, the increase in NE turnover in IBAT with this overfeeding regimen reflects enhanced central sympathetic outflow. Thus NE turnover techniques can be satisfactorily applied to the assessment of sympathetic nervous system activity in IBAT. The experiments reported here demonstrate changes in sympathetic activity in IBAT that parallel known adaptive changes in heat production in the rat. These studies, therefore, support the concept that the increased thermogenesis of chronic cold exposure and of cafeteria feeding occur by similar mechanisms and imply an important role for the sympathetic nervous system, mediated in part through BAT, in the regulation of energy balance in the rat.

Starvation suppresses sympathoadrenal medullary response to cold exposure in rats.

The effect of 2 days (55 h) of starvation on the functional state of the sympathetic nervous system (SNS) and adrenal medulla in male rats was evaluated in both normal (24 degrees C) and cold (4 degrees C) environments. Fasting (24 degrees C) significantly decreased NE turnover in heart and spleen, and the concentration of plasma epinephrine (E) and norepinephrine (NE). Cold exposure in the fed animals significantly increased NE turnover in the heart and plasma E, but had no effect on plasma NE or spleen NE turnover compared to normal (no stress) conditions. Cardiac NE turnover was 50% less in fasted cold-stressed animals than in fed cold-stressed animals. Plasma E remained at low levels. Plasma concentration of free fatty acids was significantly elevated in the fasted state in both warm and cold environments. These results suggest that 2 days of starvation in adult male rats suppresses the activity of the SNS and adrenal medulla and interferes with the normal adrenergic response to cold stress. Moreover, E appears not to be essential for mobilization of fat stores for energy metabolism in the fasted state in either warm or moderately cold environments.

Impact of age on basal and diet-induced changes in sympathetic nervous system activity of Fischer rats.

Studies were performed to assess the effect of age on basal sympathetic nervous system activity and on diet-induced changes in sympathetic activity. The rate of norepinephrine turnover in various tissues was measured as an index of sympathetic nervous system activity. In ad lib fed male Fischer 344 rats aged 3 to 24 months, there were no age-related differences in norepinephrine turnover in heart, liver, kidney or pancreas. Throughout the same age range, norepinephrine turnover was greater in organs of sucrose fed than in organs of fasted animals. Diet-induced changes in sympathetic activity thus persist throughout the age range studied.

Norepinephrine turnover in pineal gland and superior cervical ganglia. Changes after gonadotrophin administration to castrated rats.

The effects of FSH and LH on norepinephrine (NE) turnover in pineal gland and superior cervical ganglia of castrated female rats were examined by measuring the decline of [3H]NE concentration in the organ 30--120 min after a single i.v. injection of the labeled amine. Both FSH and LH treatment significantly decreased [3H]NE turnover in the pineal gland whereas only FSH accelerated it in the ganglia. As compared to controls, the initial uptake of [3H]NE was lower in the pineal gland of FSH- and LH-treated animals, and higher in the superior cervical ganglia of rats injected with FSH. Neither FSH nor LH modified [3H]NE turnover in heart or adrenal gland, nor changed their endogenous catecholamine content. Pineal monoamine oxidase (MAO) activity type B (assaying by using beta-phenylethylamine as substrate) was decreased by FSH or LH injection. Only FSH modified MAO activity in the ganglia by increasing significantly type A enzyme (assaying by using serotonin as substrate). These results suggest that FSH and LH affect significantly NE metabolism in pineal gland and superior cervical ganglia of spayed rats.

Effect of acute and chronic elevated air temperatures, constant (34 degrees) and cyclic (10--34 degrees), on brain and heart norepinephrine of male Japanese quail.

Abstract Endogenous levels and turnover of brain and heart norepinephrine (NE) of male quail ( Coturnix coturnix japonica ) were fluorometrically determined after exposure to either acute (6 hr) and chronic (5 week) 34° or cyclic temperature (10–34°) stress. α-Methyl- p -tyrosine (αMT) was used to induce depletion of endogenous norepinephrine levels by inhibition of tyrosine hydroxylase. The differences between the levels of treated and control birds (22°) were regarded as changes in turnover. High ambient temperature (34°) stress for 6 hr increased brain NE levels, decreased heart NE levels, and increased turnover of brain and heart NE. However, chronic exposure (5 weeks) to 34° and cyclic temperature (10–34°) did not increase turnover of brain NE, though chronic exposure to 34° increased heart NE turnover. The results indicate that there is increased noradrenergic activity during acute thermal exposure, and that after acclimation to thermal stress for 5 weeks, the noradrenergic activity declines in the brain, though it persists in the heart. Chronic exposure to 34° significantly reduced heart, adrenal, and testes weights, but exposure to chronic cyclic temperatures (10–34°) only reduced adrenal weight.