Role of the sympathetic nervous system in cold-induced hypertension in rats

Hypertension develops in rats exposed chronically to cold [6 +/- 2 degrees C (SE)] and includes both an elevation of mean arterial pressure and cardiac hypertrophy. Previous studies suggest that cold-exposed animals, at least initially, have a large sustained increase in the activity of their sympathetic nervous system, suggesting a failure of the baroreceptor system to provide sufficient negative feedback to the central nervous system. The present study was designed to investigate whether alterations in the activity of the sympathetic nervous system, including the baroreceptor reflex, occur during exposure to cold and whether they contribute to cold-induced hypertension. Twenty male rats were prepared with indwelling catheters in the femoral artery and vein. Ten of the rats were exposed to cold (6 +/- 2 degrees C) chronically, while the remaining 10 were kept at 26 +/- 2 degrees C. Withdrawal of arterial blood samples (less than 5 ml/kg), measurement of direct arterial pressures, and measurement of baroreflex function were carried out at 0800 h at intervals throughout the experiment. Norepinephrine and epinephrine concentrations in plasma were also determined at intervals throughout the experiment. Systolic, diastolic, and mean blood pressures of cold-exposed rats were increased to levels significantly above those of controls. The sensitivity of the baroreflex (delta heart period/delta mean arterial pressure) was decreased in the cold-treated group. The concentration of norepinephrine in plasma increased after 24 h of exposure to cold and remained elevated throughout the experiment, whereas the concentration of epinephrine in plasma increased initially but returned to control levels after 19 days of exposure to cold.(ABSTRACT TRUNCATED AT 250 WORDS)     

Hypertension during chronic exposure to cold: comparison between Sprague-Dawley and Long-Evans strains.

It is now well established that chronic exposure of rats to cold (5-6 degrees C) induces an elevation of systolic, diastolic, and mean blood pressures and cardiac hypertrophy within 3 weeks. Since rats of the Long-Evans (LE) strain are known to be resistant to the induction of deoxycorticosterone salt induced hypertension, their cardiovascular responses to chronic exposure to cold were compared with those of rats of the Sprague-Dawley (SD) strain. The results of these studies revealed clear differences between the LE and SD strains of rats. Thus, rats of the SD strain had a significant elevation in their blood pressure; a significantly increased urinary output of norepinephrine and epinephrine; a significantly greater dipsogenic responsiveness to acute administration of angiotensin II, and significant increases in weights of the heart, kidneys, adrenals, and brown adipose tissue compared with their warm-adapted controls. All of these changes are characteristic of rats acclimated to cold. In contrast, rats of the LE strain appear to be less responsive to cold in that blood pressure failed to rise as sharply and to attain as high a level. Furthermore, urinary outputs of norepinephrine and epinephrine were significantly lower in cold-treated rats of the LE strain compared with cold-treated rats of the SD strain, but dipsogenic responsiveness to angiotensin II was unchanged. Although increases in the weight of the previously mentioned organs were also observed in cold-treated rats of the LE strain compared with their warm-adapted controls, weights of the heart and interscapular brown adipose tissue of both groups were significantly less than those of counterparts of the SD strain.(ABSTRACT TRUNCATED AT 250 WORDS)     

The predominant role of brain angiotensinogen and angiotensin in environmentally induced hypertension

Rats exposed chronically to a cold environment (5 degrees C/4 degrees F) develop hypertension. This cold-induced hypertension (CIH) is a non-genetic, non-pharmacological, non-surgical model of environmentally induced hypertension in rats. The renin-angiotensin system (RAS) appears to play a role in both initiating and/or maintaining the high blood pressure in CIH. The goal of the present study was to evaluate the role of central and peripheral circulating RAS components, angiotensinogen (AGT), angiotensin-converting enzyme (ACE) and angiotensin (Ang) II, in CIH. Seventy-two Sprague-Dawley adult male rats were used. Thirty-six rats were kept in cold room at 5 degrees C while the other 36 were at 24 degrees C as controls for 5 weeks. Systolic blood pressure (SBP) was recorded by tail cuff. The SBP was increased in rats exposed to cold within 1 week, and this increase was significant for the next 2-5 weeks of the cold exposure (p<0.01). Three subgroups of the cold-treated and control rats (n=12) were sacrificed at 1, 3 and 5 weeks. The brain and liver were removed and plasma was saved. The AGT mRNA significantly increased in the hypothalamus and liver in cold-treated rats from the first week of exposure to cold, and was maintained throughout the time of exposure to cold (n=4, p<0.01). The AGT protein levels in the brain, liver and plasma did not differ significantly between cold-treated and control rats (p>0.05, n=4). The hypothalamic Ang II levels were significantly increased, whereas plasma Ang II levels significantly decreased, in the rats of 5 weeks of cold exposure (n=8, p<0.05). Plasma ACE significantly increased in the rats of 1 week of cold exposure (p<0.05, n=12). The results show differential regulation of RAS components, AGT, ACE and Ang II, between brain and periphery in cold-exposed rats. We conclude that the exposure to low temperature initially increases plasma RAS but with continuous exposure to cold, the brain RAS maintains the hypertension, probably by sustained sympathetic activation, which would provide increased metabolism but also vasoconstriction leading to hypertension.     

Human eNOS gene delivery attenuates cold-induced elevation of blood pressure in rats

We previously showed that chronic cold exposure inhibits endothelial nitric oxide synthase (eNOS) expression and decreases nitric oxide (NO) production. The aim of the present study was to evaluate the possible role of the NO system in the development of cold-induced hypertension (CIH) by testing the hypothesis that adenoviral delivery of human eNOS gene increases NO production and attenuates CIH in rats. The effect of in vivo delivery of adenovirus carrying human eNOS full-length cDNA (rAdv.heNOS) on CIH was tested using four groups of Sprague-Dawley rats (6 rats/group). Blood pressure (BP) did not differ among the four groups during the control period at room temperature (24 degrees C). Two groups of rats received intravenous injection of rAdv.heNOS (1 x 10(9) plaque-forming units/rat), and the other two groups received the same dose of rAdv.LacZ to serve as controls. After gene delivery, one rAdv.heNOS-treated group and one rAdv.LacZ-treated group were exposed to cold (6 degrees C) while the remaining groups were kept at 24 degrees C. We found that the BP of the rAdv.LacZ group increased significantly within 1 wk of exposure to cold and reached a peak level at week 5 (152.2 +/- 6.4 mmHg). In contrast, BP (118.7 +/- 8.4 mmHg) of the cold-exposed rAdv.heNOS group did not increase until 5 wk after exposure to cold. The rAdv.heNOS increased plasma and urine levels of NO significantly in cold-exposed rats, which indicates that eNOS gene transfer increased NO production. Notably, rAdv.heNOS decreased plasma levels of norepinephrine and plasma renin activity in cold-exposed rats, which suggests that eNOS gene transfer may decrease the activities of the sympathetic nervous system and the renin-angiotensin system. Immunohistochemical analysis showed that the transferred human eNOS was expressed in both endothelium and adventitia of mesenteric arteries. We conclude that 1) eNOS gene transfer attenuates CIH by increasing NO production and inhibiting the sympathetic nervous system and the renin-angiotensin system; and 2) the NO system appears to mediate this nongenetic, nonpharmacological, nonsurgical model of hypertension.     

Increased tail artery vascular responsiveness to angiotensin II in cold-treated rats

Chronic exposure of rats to cold for 1-3 weeks results in a mild form of hypertension. The renin-angiotensin system (RAS) has been implicated in this model of cold-induced hypertension. Previously we have characterized the vascular responsiveness in cold-acclimated animals, using aortic tissue, and recent studies have focused on the thermoregulatory responses of angiotensin II (AngII), utilizing the tail artery of the rat. Therefore in the current study we evaluated the vascular responsiveness of cold-treated rats to AngII in both aorta and tail artery at 2 and 4 weeks of cold exposure (5+/-2 degrees C). Systolic blood pressures were significantly elevated in cold-treated animals compared with control animals at both 2 and 4 weeks of cold exposure. At both of these time points body weights were reduced and ventricular weights were increased in cold-treated animals. After 2 weeks of cold exposure the vascular responsiveness of the aorta to AngII was significantly lower than that of controls. This vascular responsiveness to AngII was elevated and returned to control levels after 5 weeks of cold exposure. However, this pattern was not observed in the tail artery. The vascular responsiveness of tail artery rings from cold-treated rats to AngII was significantly greater than that of control animals during both 2 and 5 weeks of exposure to cold. The vascular contractile responses of both the aorta and tail artery to KCI in the cold-treated animals was not different from that of the control animals maintained at ambient room temperature, suggesting that the vascular smooth muscle contractile components were not altered by the cold exposure. Thus, the in vitro vascular reactivity to the receptor-mediated vasoconstrictor AngII was decreased in the sparsely innervated aorta and increased in the more densely innervated tail artery of the cold-treated animals when compared with controls. These results suggest that the increased responsiveness of AngII on the smooth muscle of the tail artery may play a role in adaptation to the cold and the maintenance of cold-induced hypertension.     

Interaction between exercise training and cold acclimation in rats

Five groups of 10 rats were used. Group A included sedentary rats kept at 24 degrees C, group B exercised-trained rats and group C rats exposed at -15 degrees C for 2 h every day and kept at 24 degrees C for the remaining time. These 3 groups were kept on this regimen for 10 weeks. In addition group D was acclimated to cold (2 h.d-1 at -15 degrees C) for 6 weeks and subsequently deacclimated at 24 degrees C for 4 weeks. Group E was also acclimated to cold for 6 weeks and during the deacclimation, at 24 degrees C period which lasted 4 weeks, the animals were exercised 2 h per day. Following the 10 week experimental period all animals were sacrificed and DNA and protein content of the IBAT as well as its total mass were measured. The results show significant increases in the cold adapted group. Exercise training which had no effect on brown adipose tissue IBAT at room temperature, caused an accelerated reduction in weight, DNA and protein content of the BAT in rats previously acclimated to cold. In spite of this, the thermogenic response to noradrenaline was significantly enhanced in the group which exercised during the deacclimation period. It is suggested that tissues other than IBAT may explain this enhanced heat production capacity.     

Neonatal chemical sympathectomy attenuates fructose-induced hypertriglyceridemia and hypertension in rats

Experiments were performed to determine the pathogenic contribution of the peripheral sympathetic nervous system to fructose-induced hypertriglyceridemia, hyperinsulinemia and hypertension in rats. Neonatal chemical sympathectomy was performed in neonatal Sprague-Dawley rats (1-week old) by administration of guanethidine (50 microg/g, i.p.) 5 times per week for consecutive 3 weeks and nerve-intact rats were served as controls. Both groups of rats were fed a fructose-enriched diet for 9 weeks. The systolic blood pressure (SBP) and body weight were measured weekly and arterial blood samples were taken weekly for determinations of plasma insulin, glucose and triglyceride levels. The results showed that fructose feeding for one week significantly increased SBP in intact rats and sympathectomized rats (116+/-1 to 119+/-1 mmHg and 116+/-1 to 120+/-1 mmHg, respectively). SBP further increased thereafter in both groups. However, the increased SBP levels were significantly higher in intact group than in sympathectomized group after 5 weeks of fructose feeding. Fructose feeding for one week concurrently produced hypertriglyceridemia that preceded the appearance of hyperinsulinemia in both groups. The elevated plasma triglyceride levels were significantly lower in sympathectomized rats than in intact rats after 3 weeks of fructose feeding, whereas the elevated plasma insulin concentrations were not different between groups throughout fructose feeding period. Plasma glucose concentrations of both groups were comparable and remained unchanged throughout the study. These data indicate that neonatal chemical sympathectomy attenuated, but did not prevent, fructose-induced elevations in blood pressure and plasma triglyceride levels, suggesting a partial dependency of fructose-induced hypertriglyceridemia and hypertension on the integrity of the peripheral sympathetic nervous system (SNS) in rats.     

Development of deep hypothermia in rats with limited motor activity

Changes of the main organism functions (breathing frequency, heart rate and shivering) were investigated under hypothermia in two groups of rats. Animals of the first group were fixed rigidly on the special platform with fixing of head and limbs, and those of the second one--the rats, were placed in a punched cylindrical chamber, inside which they could move freely forward and back. In 2.5-3.0 hours after anaesthesia the rats were placed in a refrigerator (-5 degrees C) until they stop breathing. Cessation of breathing of the first group rats occurred in 1.7 +/- 0.3 hours from the beginning of cooling at body temperature 17.3 +/- 0.6 degrees C and the brain temperature 15.7 +/- 0.5 degrees C. In the second group, a prolonged activation of the frequency of breathing, heart rate and intensity of electrical activity of muscles during 2.5-3.0 hours, was observed. Only in 4.5-5.0 hours, the breathing stopped at rectal temperature 12.3 +/- 1.1 degrees C and the brain temperature 12.9 +/- 0.9 degrees C. In these animals, the time of survival in the cold environment increased considerably and the temperature thresholds of the termination of breathing were lowered. Thus, the activation in the thermo-regulative muscle tone and in shivering muscles provides the most effective resistance against cooling of rats, reducing a surface of heat, dissipation and keeping the temperature of internal areas of body.     

Effect of a reduction in sodium intake on cold-induced elevation of blood pressure in the rat.

Chronic exposure of rats to cold (5 degrees C) induces hypertension within 3 weeks. The objective of this study was to determine the effect of treatment with graded levels of dietary NaCl on the induction of hypertension during chronic exposure to cold. Four groups of male rats were used. The first, given a commercial sodium-deficient diet containing 0.30% NaCl, served as the warm-adapted control group. The second, third, and fourth groups were given the same diet containing 0.075%, 0.15%, and 0.30% NaCl, respectively. Because cold-exposed rats ingest approximately twice as much food as warm-adapted controls, this represented half, the same, and twice the amount of NaCl ingested by the control group. The latter three groups were placed in cold air (5 degrees C). All cold-treated groups had an elevation of systolic blood pressure that was proportional to the concentration of NaCl in the diet by the seventeenth week of exposure to cold. Cardiac hypertrophy occurred to the same extent in all cold-exposed groups and was thus unaffected by the NaCl content of the diet or by the extent of elevation of blood pressure. Hence, cardiac hypertrophy during chronic exposure to cold is supported by other factors, possibly by the increased concentration of either norepinephrine or triiodothyronine, or both, which occurs characteristically in rats under these conditions. The results of this experiment suggest that the amount of NaCl ingested daily plays a role in the cold-induced elevation of blood pressure observed in rats.     

Perception of foot temperature in young women with cold constitution: analysis of skin temperature and warm and cold sensation thresholds

To examine the disease state of cold constitution, physiological measurements of the foot were conducted by investigating thermal sensations under an environmental condition of 25 degrees C-26 degrees C (neutral temperature) in 29 young women with and without cold constitution. The subjects were classified into 3 groups according to their experiences with cold constitution: cold constitution, intermediate, and normal groups. Foot skin temperature was measured by thermography. Thermal sensations were measured on the dorsum of the left foot using a thermal stimulator. Cold and warm spots on the dorsum of the right foot were ascertained. Thermal stimulation was delivered by a copper probe. No significant differences in foot skin temperature among these 3 groups were identified as measured in a laboratory under neutral temperature conditions. However, the mean warm sensation threshold was +6.3+/-1.09 degrees C (mean+/-SEM) for the cold constitution group (n=14), +3.4+/-2.10 degrees C (mean+/-SEM) for the intermediate group (n=7), and -0.25+/-1.96 degrees C (mean+/-SEM) for the normal group (n=6). The difference was significant between the cold constitution and normal groups. No significant differences among the 3 groups were found in the cold sensation threshold. This may be attributable to the distribution of thermal receptors and to chronically reduced blood flow in subcutaneous tissues, where the skin temperature receptors responsible for temperature sensation are located.     

Homeostatic responses to caloric restriction: influence of background metabolic rate.

The biological responses to caloric restriction (CR) are generally examined in rats with elevated metabolic rates due to being housed at ambient temperatures (T(a)) below the zone of thermoneutrality. We determined the physiological and behavioral responses to 2 wk of 30-40% CR in male FBNF1 rats housed in cool (T(a) = 12 degrees C) or thermoneutral (TMN; T(a) = 30 degrees C) conditions. Rats were instrumented with telemetry devices and housed continuously in home-cage calorimeters for the entire experiment. At baseline, rats housed in cool T(a) had reduced rate of weight gain; thus a mild CR (5%) group at thermoneutrality for weight maintenance was also studied. Rats housed in cool T(a) exhibited elevated caloric intake (cool = 77 +/- 1; TMN = 54 +/- 2 kcal), oxygen consumption (Vo(2); cool = 9.9 +/- 0.1; TMN = 5.5 +/- 0.1 ml/min), mean arterial pressure (cool = 103 +/- 1; TMN = 80 +/- 2 mmHg), and heart rate (cool = 374 +/- 3; TMN = 275 +/- 4 beats/min). Cool-CR rats exhibited greater CR-induced weight loss (cool = -62 +/- 3; TMN = -42 +/- 3 g) and reductions in Vo(2) (cool = -2.6 +/- 0.1; TMN = -1.5 +/- 0.1 ml/min) but similar CR-induced reductions in heart rate (cool = -59 +/- 1; TMN= -51 +/- 7 beats/min). CR had no effect on arterial blood pressure or locomotor activity in either group. Unexpectedly, weight maintenance produced significant reductions in Vo(2) and heart rate. At thermoneutrality, a single day of refeeding effectively abolished CR-induced reductions in Vo(2) and heart rate. The results reveal that rats with low or high baseline metabolic rate exhibit comparable compensatory reductions in Vo(2) and heart rate and suggest that T(a) can be used to modulate the metabolic background on which the more prolonged effects of CR can be studied.     

Effects of chronic cold exposure on the endothelin system.

Cold temperatures have adverse effects on the human cardiovascular system. Endothelin (ET)-1 is a potent vasoconstrictor. We hypothesized that cold exposure increases ET-1 production and upregulates ET type A (ETA) receptors. The aim of this study was to determine the effect of cold exposure on regulation of the ET system. Four groups of rats (6-7 rats/group) were used: three groups were exposed to moderate cold (6.7 +/- 2 degrees C) for 1, 3, and 5 wk, respectively, and the remaining group was maintained at room temperature (25 degrees C) and served as control. Cold exposure significantly increased ET-1 levels in the heart, mesenteric arteries, renal cortex, and renal medulla. Cold exposure increased ETA receptor protein expression in the heart and renal cortex. ET type B (ETB) receptor expression, however, was decreased significantly in the heart and renal medulla of cold-exposed rats. Cold exposure significantly increased the ratio of ETA to ETB receptors in the heart. An additional four groups of rats (3 rats/group) were used to localize changes in ETA and ETB receptors at 1, 3, and 5 wk of cold exposure. Immunohistochemical analysis showed an increase in ETA, but a decrease in ETB, receptor immunoreactivity in cardiomyocytes of cold-exposed rats. Increased ETA receptor immunoreactivity was also found in vascular smooth muscle cells of cold-exposed rats. Cold exposure increased ETA receptor immunoreactivity in tubule epithelial cells in the renal cortex but decreased ETB receptor immunoreactivity in tubule epithelial cells in the renal medulla. Therefore, cold exposure increased ET-1 production, upregulated ETA receptors, and downregulated ETB receptors.     

Factors affecting cold-induced hypertension in rats

A 3- to 4-week exposure of rats to a cold environment (5 +/- 2 degrees C) induces hypertension, including elevation of systolic, diastolic, and mean blood pressures and cardiac (left ventricular) hypertrophy. The studies described here were designed to investigate some factors affecting both the magnitude and the time course for development of cold-induced hypertension. The objective of the first study was to determine whether there was an ambient temperature at which the cold-induced elevation of blood pressure did not occur. The objective of the second experiment was to determine whether body weight at the time of exposure to cold affected the magnitude and time course for development of hypertension. To assess the first objective, male rats were housed in a chamber whose temperature was maintained at 5 +/- 2 degrees C while others were housed in an identical chamber at 9 +/- 2 degrees C. After 7 days of exposure to cold, the rats exposed to the colder temperature had a significant elevation of blood pressure (140 +/- 2 mm Hg) compared with the group maintained at 9 degrees C (122 +/- 3 mm Hg). The rats exposed to 9 degrees C had no significant elevation of systolic blood pressure at either 27 or 40 days after initiation of exposure to cold. At the latter time, the temperature in the second chamber was reduced to 5 +/- 2 degrees C. By the 25th day of exposure to this ambient temperature, the rats had a significant increase in systolic blood pressure above their levels at 9 degrees C. Thus, there appears to be a threshold ambient temperature for elevation of blood pressure during exposure to cold. That temperature appears to lie somewhere between 5 and 9 degrees C. The second objective was assessed by placing rats varying in weight from approximately 250 to 430 g in air at 5 degrees C. There was a highly significant direct relationship (r = 0.96) between body weight at the time of introduction to cold and the number of days required to increase systolic blood pressure by 10 mm Hg above pre-cold exposure level. The third objective was to make an initial assessment of potential differences among strains of rats with respect to development of cold-induced hypertension. To this end, rats of the Fischer 344 strain were used. Systolic blood pressures of these rats also increased during chronic exposure to cold.(ABSTRACT TRUNCATED AT 400 WORDS)     

Effects of cold acclimation on the activity levels of creatine kinase, lactate dehydrogenase and lactate dehydrogenase isoenzymes in various tissues of the rat.

The effects of cold acclimation on the activity levels of creatine kinase, lactate dehydrogenase and lactate dehydrogenase isoenzymes in various tissues/ organs of the rat (Rattus norvegicus) were investigated. Male Sprague-Dawley rats were divided into two groups. One group was housed at 4+/-1 degrees C (experimental group) and the other at 24+/-1 degrees C (control group) for six months. The rats were housed in single cages and had access to food and water ad libitum. The tissues/organs investigated were heart, liver, lung, kidney, gastrocnemius muscle and interscapular brown adipose tissue as well as serum. With the exception of lung, (which showed a decrease of 24%) total creatine kinase activity levels were significantly increased (P< 0.05) in all the tissues/organs investigated (17-51%) as well as serum (34%), in cold acclimated animals. Cold acclimation also resulted in significantly increased (P< 0.05) activity levels of lactate dehydrogenase in all the tissues/organs investigated (14-24%) as well as serum (35%). Cold exposure resulted in an increase of the activity levels of all the detectable isoenzymes of lactate dehydrogenase, although not always significant, in all the tissues/organs investigated as well as serum. The M(4)tetramer of lactate dehydrogenase was the only detectable isoenzyme in serum.     

Effect of temperature on lipoprotein lipase and lipogenic enzyme activities in brown adipose tissue of hypophysectomized rats

It has been shown that the same modifications on the composition of brown adipose tissue (BAT) which are normally induced following cold stimulation are also observed in hypophysectomized rats acclimated either at 28 degrees C or 15 degrees C. To test the possibility of BAT stimulation in hypophysectomized rats, we have determined some enzymatic activities known to modulate the energy supply to that organ. Seven week old Long-Evans rats were hypophysectomized. Three weeks later, they were exposed to either 28 degrees C or 15 degrees C ambient temperature for five or six weeks. Hypophysectomized rats were compared to age matched or weight matched controls. Total lipoprotein lipase activity (LPL) (triglyceride uptake) was enhanced in BAT of 28 degrees C hypophysectomized rats compared to controls. Cold acclimation led to a large increased activity. Total LPL activity was comparable in BAT of hypophysectomized and control rats. Total malic enzyme and glucose-6-phosphate dehydrogenase activities (in situ lipogenesis) were doubled in BAT of 28 degrees C hypophysectomized compared to controls. A large enhancement was observed in BAT of either 15 degrees C control or 15 degrees C hypophysectomized rats. Among the studied organs (liver, white adipose tissue, heart, BAT) hypophysectomy promotes the three enzyme activities only in BAT. These variations were discussed with relation to the effect of hypophysectomy on brown adipose tissue at 15 degrees C and 28 degrees C.     

Central angiotensin receptor blockade impairs thermolytic and dipsogenic responses to heat exposure in rats

The effect of central angiotensin AT(1) receptor blockade on thermoregulation and water intake after heat exposure was investigated. Rats were placed in a chamber heated to 39 +/- 1 degrees C for 60 min and then returned to their normal cage (at 22 degrees C), and water intake was measured for 120 min. Artificial cerebrospinal fluid (5 microl) was injected intracerebroventricularly 60 min before heat exposure in five control rats. Colonic temperature increased from 37.22 +/- 0.21 to 40.68 +/- 0.31 degrees C after 60 min. In six rats injected intracerebroventricularly with 10 microg of the AT(1) antagonist losartan, colonic temperature increased from 37.41 +/- 0.27 to 41.72 +/- 0.28 degrees C after 60 min. This increase was significantly greater than controls (P < 0.03). Losartan-treated rats drank 1.1 +/- 0.4 ml of water compared with 5.9 +/- 0.77 ml (P < 0.002) drank by control animals, despite a similar body weight loss in the two groups. Central losartan did not inhibit the drinking response to intracerebroventricular carbachol in heated rats, suggesting that losartan treatment did not nonspecifically depress behavior. We conclude that central angiotensinergic mechanisms have a role in both thermoregulatory cooling in response to heat exposure and also the ensuing water intake.     

Pulmonary vascular responsiveness in cold-exposed calves

The pulmonary vascular responses to acute hypoxia and to infusions of histamine and 5-hydroxytryptamine (5-HT) were recorded in unanesthetized standing bull calves under neutral (16-18 degrees C) and cold (3-5 degrees C) temperature conditions. Cold exposure alone resulted in a significant increase in pulmonary arterial wedge pressure from 10.2 +/- 3.5 to 15.9 +/- 4.9 Torr (1 Torr = 133.322 Pa). Resistance to blood flow between the pulmonary wedge and the left atrium significantly increased from 0.50 +/- 0.51 to 1.21 +/- 0.78 mmHg . L-1 . min-1 (1 mmHg = 133.322 Pa) with cold exposure. This apparent pulmonary venoconstrictor response to cold exposure was further evaluated to determine if hypoxia, histamine, or 5-HT responsiveness was altered by cold exposure. Twelve minutes of hypoxia increased pulmonary arterial and systemic arterial pressures, heart rate, and respiratory rate similarly in cold and neutral temperatures. Cold exposure did not alter the dose-related reductions of systemic arterial and pulmonary arterial pressures in response to histamine. Similarly, the decreases in systemic arterial pressure and heart rate and increases in pulmonary arterial and left atrial pressures in response to 5-HT were not significantly different in cold and neutral conditions. It was concluded that acute, mild cold exposure results in an increase in resistance to blood flow in the pulmonary venous circulation without a general increase in pulmonary vascular reactivity, as measured by responses to hypoxia, histamine, and 5-HT.     

Baroreflex control of muscle sympathetic nerve activity in postural orthostatic tachycardia syndrome

Postural orthostatic tachycardia syndrome (POTS) is characterized by excessive tachycardia during orthostasis. To test the hypothesis that patients with POTS have decreased sympathetic neural responses to baroreflex stimuli, we measured heart rate (HR) and muscle sympathetic nerve activity (MSNA) responses to three baroreflex stimuli including vasoactive drug boluses (modified Oxford technique), Valsalva maneuver, and head-up tilt (HUT) in POTS patients and healthy control subjects. The MSNA response to the Valsalva maneuver was significantly greater in the POTS group (controls, 26 +/- 7 vs. POTS, 48 +/- 6% of baseline MSNA/mmHg; P = 0.03). POTS patients also had an exaggerated MSNA response to 30 degrees HUT (controls, 123 +/- 24 vs. POTS, 208 +/- 30% of baseline MSNA; P = 0.03) and tended to have an exaggerated response to 45 degrees HUT (controls, 137 +/- 27 vs. POTS, 248 +/- 58% of baseline MSNA; P = 0.10). Sympathetic baroreflex sensitivity calculated during administration of the vasoactive drug boluses also tended to be greater in the POTS patients; however, this did not reach statistical significance (P = 0.15). Baseline MSNA values during supine rest were not different between the groups (controls, 23 +/- 4 vs. POTS, 16 +/- 5 bursts/100 heartbeats; P = 0.30); however, resting HR was significantly higher in the POTS group (controls, 58 +/- 3 vs. POTS, 82 +/- 4 beats/min; P = 0.0001). Our results suggest that POTS patients have exaggerated MSNA responses to baroreflex challenges compared with healthy control subjects, although resting supine MSNA values did not differ between the groups.     

Attenuation of psychosocial stress-induced hypertension by gamma-linolenic acid (GLA) administration in rats

This study investigated a model of psychosocial stress-induced hypertension in the rat, and examined effects of the prostaglandin E precursor, gamma-linolenic acid (GLA) on the development of hypertension during psychosocial stress. In the first study, male rats were housed four/cage for an acclimation period of 21 days, followed by a 14-day control period. An experimental group (N = 12) was then placed in isolation cages for 14 days, then regrouped for a 7-day recovery period. Controls (N = 12) remained group-housed. Eight animals per group were sacrificed after the experimental period, and four per group after recovery for organ weight analysis. Mean systolic blood pressure (BP) was similar between groups during the control period (126 +/- 2 and 125 +/- 2 mm Hg), but increased during isolation, reaching 140 +/- 2 mm Hg (P less than 0.001) by Day 14. During recovery BP returned to control levels. No changes in heart rate, heart weight/body weight or adrenal weight were seen. The second study utilized a protocol similar to that of the experimental group of the first study, minus the recovery period. On Day 1 of the control period 28-day osmotic pumps were implanted ip, releasing olive oil or GLA in olive oil. Four groups of rats (N = 8/group) received either (i) olive oil (controls), (ii) 0.018 mg GLA/hr, (iii) 0.040 mg GLA/hr, or (iv) 0.040 mg GLA/hr with no stress. Organ weights were obtained following stress in groups 1-3. Controls developed a sustained elevation in BP within 24 hr of isolation. Animals receiving 0.018 mg GLA/hr developed elevated BP upon isolation, but the BP was less than that of controls on Days 1 (P less than 0.05) and 14 (P less than 0.001) of isolation. Animals receiving 0.040 mg GLA/hr demonstrated a greatly attenuated rise in BP vs controls (P less than 0.001) on all isolation days. GLA in unstressed rats had no effect on BP. Heart rate, heart weight/body weight, and adrenal weight were unchanged in all groups. These data suggest that (i) isolation is a useful tool for investigating reversible psychosocial stress-induced hypertension, and (ii) GLA, while not affecting BP in unstressed animals, produces a dose-dependent attenuation of the BP response to chronic stress.