Hypotension and thirst in rats after phentolamine treatment

Administration of the α-adrenergic receptor blocker phentolamine is known to lower arterial blood pressure and to increase renin secretion and water intake in rats. In the present experiments, drinking by rats after subcutaneous administration of the drug was found to be inversely related to arterial blood pressure within the range of 60–90 mm Hg. Drug treatment in nephrectomized rats led to such severe hypotension that drinking was precluded. Pretreatment with propranolol moderated the hypotension in nephrectomized rats and drinking was not attenuated. These results parallel those of previous experiments using the β-adrenergic receptor agonist isoproterenol. Collectively, they suggest that after treatment with these hypotensive agents, a stimulus for thirst can arise from some factor other than angiotensin. This stimulus, perhaps mediated by arterial baroreceptors, is additive in its effects on thirst with the stimulus induced by hypertonic NaCl or subcutaneous colloid treatments.     

Increased hunger and thirst during glucoprivation in humans

Five male volunteers received two intravenous infusions of 2-deoxy-D-glucose (2DG) and one of normal saline. Hunger and thirst ratings, solid-food and water intake, and plasma epinephrine and glucose levels were greater after both of the 2DG infusions than after the saline infusion. This study suggests that the increase in water intake caused by 2DG does not depend on elevated hunger, and demonstrates that increased caloric intake after 2DG infusions is not dependent on greater thirst. Behavioral and adrenomedullary responses to both 2DG infusions were qualitatively and quantitatively the same, suggesting that there are no residual effects of 2DG that diminish the ability of the subjects to respond to glucoprivation. Measurements of possible thirst stimuli revealed no clear mechanism for the dipsogenic effect of 2DG.     

Water intake regulation in rats after intestinal bypass surgery

Jejunoileal bypass surgery in normal-weight female rats produced a temporary reduction in food intake, and small but more long lasting reductions in water intake and the water to food intake ratio. The bypass rats, however, did not differ from controls in their drinking response in a variety of thirst tests. That is, the bypass rats displayed normal increases in water intake following 24 hr water deprivation, hypertonic saline injection, or injection of polyethylene glycol; and normal decreases in water intake when food deprived or when given quinine-adulterated water. On the other hand, the bypass rats did not drink as much as did the controls when offered isotonic saline, or a saccharin solution for 24 hr/day, or when tested for schedule-induced-polydipsia 3 hr/day. The results indicate that bypassing a large segment of the jejunum and ileum does not disrupt regulatory drinking in the rat, but it does limit their ability to consume large volumes of fluid.     

The nature of the thirst stimulus: a factor in conditioned taste-aversion behavior.

Independent groups of rats were compared drinking in response to either water deprivation or osmotic thirst induced by intraperitoneal injections of hypertonic saline. When water or a palatable saccharin solution served as the drinking fluid, deprivation and osmotic thirst produced comparable fluid intakes. In contrast, when a saccharin solution previously associated with the aversive effects of lithium served as the drinking fluid, animals injected with hypertonic saline drank substantially less than water deprived animals. Experiment 2 indicated that this hyperreactivity to a conditioned aversive flavor in animals suffering from osmotic thirst was due to the reduced palatability of the saccharin flavor rather than the previous experience with lithium. Experiment 3 showed that the effect also could not be attributed to differential taste-aversion learning, handling, food deprivation or weight loss before the test sessions. The phenomenon is discussed in terms of various differences between thirst induced by water deprivation and thirst induced by acute cellular dehydration.     

Plasma and cerebrospinal fluid vasopressin and osmolality in relation to thirst

Conscious dogs chronically implanted with a device for cerebrospinal fluid (CSF) sampling from the anterior 3rd ventricle were submitted to 24 h dehydration. During rehydration by drinking the total water intake (TWI) after 16 min was determined in 8 and after 90 min in 14 experiments. Samples were simultaneously drawn to determine the osmolalities (P_osm, CSF_osm) and AVP concentrations (P_VVP, CSF_AVP) of plasma and CSF. After 24 h dehydration all of these parameters were significantly elevated in comparison to euhydrated dogs investigated on 19 occasions. In 8 experiments 60% of the final TWI had been ingested within the first 16 min with no changes of P_osm, CSF_osm and CSF_AVP, but a significant decrease of P_AVP at this time. TWI per kg body weight (TWI·kg^–1) after 90 min was significantly correlated with the osmolalities and AVP levels in plasma and CSF prior to rehydration. The decreases of P_osm, CSF_osm and P_AVP, but not of CSF_AVP, were significantly correlated with TWI·kg^–1. The results indicate that P_AVP and CSF_AVP are subject to long term control by body fluid tonicity exhibiting a feedback relationship to water intake. In addition, P_AVP but not CSF_AVP seems to be under short term, possibly nonosmotic, control during water intake.Supported by the Alexander von Humboldt-Foundation     

Differential effects of estradiol on drinking by ovariectomized rats in response to hypertonic NaCl or isoproterenol: Implications for hyper- vs. hypo-osmotic stimuli for water intake

We examined the effects of estradiol on behavioral responses to osmotic challenges in ovariectomized (OVX) rats to test the hypothesis that estradiol enhances sensitivity to gradual changes in plasma osmolality (pOsm) in stimulating water intake. Despite comparably elevated pOsm after a slow infusion of 2 M NaCl, the latency to begin water intake was significantly less in estradiol-treated OVX rats compared to that in oil vehicle-treated rats. Other groups of OVX rats were injected with isoproterenol, which increases circulating angiotensin II. These rats then were given 0.15 M NaCl to drink instead of water, to prevent decreased pOsm associated with water ingestion. Isoproterenol stimulated 0.15 M NaCl intake by both groups; however, estradiol-treated rats consumed less 0.15 M NaCl than did oil-treated rats, findings that are similar to those reported when estradiol-treated rats consumed water. The estradiol enhancement of sensitivity to increased, but not to decreased, pOsm suggests that estradiol has directionally-specific effects on osmoregulatory drinking. Moreover, the estradiol attenuation of 0.15 M NaCl intake after isoproterenol suggests that estradiol effects on osmoregulatory drinking are independent of those on volume regulatory drinking.     

Reduced thirst in old, thermally dehydrated rats

Water intake and blood parameters of young (7-month) and old (23-month) male Brown Norway rats were assessed following a period of thermal dehydration. Rats of both ages were randomly assigned to one of three groups: (1) Unheated-blood sample, (2) Heated-blood sample, and (3) Heated-water intake. The colonic temperature of heated rats was raised at the rate of 0.05 degrees C/min for 1 h using an infrared heat lamp. Water intake was then measured over the following 2 h. The heating protocol resulted in a similar level of dehydration in both young and old rats; however, plasma osmolality and sodium concentration increased to a significant extent only in the young rats. Old rats drank significantly less water at all time points during the 2 h following the heat stress. While neither group replaced the water lost as a result of the thermal dehydration, the young rats did rehydrate to a greater extent. These results suggest that the diminished level of rehydration in aged rats, following a thermal dehydration, is due to an attenuated rise in plasma osmolality.     

Lack of cardiotoxic effect of isoproterenol in streptozotocin diabetic rats

Summary The well known cardiotoxic effect of isoproterenol (ISO) was investigated in normal and streptozotocin diabetic rats. Seven days after the subcutaneous injection of ISO (15 mg/kg) the hearts were perfusion fixed and 12 sections from each heart were stained (Masson's trichrome). ISO induced myocardial fibrosis was quantified at the light microscopic level according to established morphometric principles. Pulse rate and ST elevation were recorded by EEC (3 standard leads) before and after the ISO injection. Non-diabetic control animals showed marked fibrosis after ISO, but surprisingly the diabetic animals showed no fibrosis after ISO treatment. These findings were in accordance with an ISO induced ST elevation seen only among control animals although both groups showed the same degree of tachycardia. Insulin treatment prevented the protection against ISO and when streptozotocin was injected 24 h after the ISO a normal quantitative and qualitative appearance of the scar tissue was seen. It thus seems that streptozotocin diabetic rats are protected against the toxic effect of ISO, leaving the haemodynamic response unaffected. Which factor in the diabetic metabolism is reponsible for the present phenomenon is not known, but a defect in the signal transmission from the -receptor to the adenylcyclase is suggested as a possible explanation.     

Inhibition of thirst in rats following hypovolemia and-or caval ligation

Thirst was elicited in rats by subcutaneous injections of a hyperoncotic polyethylene glycol (PG) solution or by infrahepatic ligation of the inferior vena cava (IVC). Rats given either treatment drank throughout the 24 hr test period when 0.15 m NaCl was the only fluid available but decreased drinking significantly within 6–8 hr when given only water. This inhibition of thirst was associated with an excessive accumulation of ingested water during oliguria. Inhibition cannot be attributed to a general osmotic dilution since plasma osmolalities actually were elevated due to the retention of urea. Instead, the inhibitory mechanism may involve reduction of the effective osmotic pressure of body fluids and cellular overhydration. Rats drinking water following combined IVC ligation and PG injection treatments required a greater degree of cellular overhydration to inhibit drinking than rats given either treatment alone. When saline was presented instead of water, the complex stimulus for thirst elicited more drinking with fluid retention than any other experimental procedure known. The extreme potency of this preparation reflects the comparable strength of the inhibitory mechanisms associated with cellular overhydration.     

Acute insulin treatment normalizes the resistance to the cardiotoxic effect of isoproterenol in streptozotocin diabetic rats

Summary The acute effect of insulin treatment on the earlier reported protective effect of streptozotocin diabetes against the cardiotoxic effect of high dosis of isoproterenol (ISO) was investigated in rats. Thirty to 135 min after the injection of crystalline insulin, ISO was given subcutaneously and when ISO induced fibrosis in the myocardium was morphometrically analyzed 7 days later, a highly significant correlation (r= 0.83, 2 p=0.006) to the slope of the fall in blood glucose after insulin treatment appeared. The myocardial content of catecholamines was estimated in these 8 day diabetic rats. The norepinephrine content was significantly increased while epinephrine remained unchanged. An enhanced sympathetic nervous system activity with a consequent down regulation of the myocardial-adrenergic receptors could, therefore, explain this catecholamine resistance. The rapid reversion after insulin treatment excludes the possibility that streptozotocin in itself causes the ISO resistance and points towards a direct insulin effect on myocardial catecholamine sensitivity in diabetic rats. The phenomenon described might elucidate pathogenetic mechanisms behind toxic myocardial cell degeneration and may possibly have relevance for acute cardiovascular complications in diabetic patients.     

Endocannabinoids protect cerebral cortical neurons from in vitro ischemia in rats

Activation of the ventrolateral periaqueductal gray (vlPAG) evokes a reaction of quiescence, immobility, hypotension and bradycardia. Pain of deep somatic or visceral origin also often triggers a reaction of quiescence, immobility, hypotension and bradycardia and further, evokes a selective increase in immediate-early-gene (c-Fos) expression within the vlPAG. Vasodepression evoked from the vlPAG is thought to be mediated by an inhibition of presympathetic neurons within the rostral ventrolateral medulla (RVLM). In this study the prior injection of retrograde tracer into the RVLM was combined with the use of Fos expression as a marker of neuronal activation, to determine if deep (muscle) pain-evoked vasodepression could be mediated by a direct vlPAG-RVLM pathway. It was revealed that intramuscular injection of formalin, in the anaesthetised rat, evoked a significant increase in Fos expression within the caudal vlPAG, and that approximately 25% of the Fos-immunoreactive neurons projected to the RVLM.     

Apomorphine-induced restoration of drinking to thirst challenges in 6-hydroxydopamine-treated rats.

After bilateral injections of 6-hydroxydopamine along the ascending DA fibers or after lateral hypothalamic electrocoagulation, rats become aphagic and adipsic, and do not drink in response to hypertonic saline or isoproterenol. However, after low doses of the DA-receptor stimulating agent, apomorphine, 6-OH-DA lesioned rats drink near-normal quantities of water in a 30 min test following either regulatory challenge. Apomorphine does not restore drinking to these thirst stimuli in rats with lateral hypothalamic electrocoagulations. These findings (1) provide additional evidence that the ingestive impairments seen after 6-OH-DA injections are due to degeneration of DA-containing neurons, and (2) suggest that the lateral hypothalamic electrocoagulation is functionally different from a specific lesion of DA neurons, possibly by interrupting striatal efferent pathways in addition to the DA afferent fibers. The interruption of these striatal efferents may explain why apomorphine does not restore drinking in the animal with lateral hypothalamic lesions.     

Graded levels of hemorrhage, thirst and angiotensin II in the rat.

Hemorrhage was evaluated as a stimulus to drink in rats prepared with chronically implanted jugular cannulae and bled either 20, 30, 40 or 50 percent of their total blood volume. Hourly observations of water intake for 5 hr after hemorrhage revealed that the volume drunk was proportional to the degree of hemorrhage. Drinking induced by 20 percent hemorrhage did not differ significantly from control values, and intake was greatest and most persistent after 50 percent blood loss. The onset of maximal drinking at 1 hr after 40 percent hemorrhage was preceded by a twofold increase in plasma concentrations of angiotensin II. This is compatible with previous suggestions that angiotensin plays a role in hypovolemic thirst.     

Interaction of hunger and thirst in rats with lesions of the preoptic area

In the rat stimuli which increase thirst decrease feeding. This study investigated the possibility that the suppression of feeding by hypertonic saline is mediated by the preoptic area. Feeding in rats with lesions in the lateral preoptic area was suppressed by increased osmolality even though these rats did not drink to hypertonic saline. Some of these rats with lesions in the preoptic area did not drink to the extracellular thirst stimulus, isoproterenol, but feeding was suppressed by the substance. Therefore the suppression of feeding by hypertonic saline and isoproterenol can be separated from the effect of these substances on water intake. It is unlikely that the interaction between hunger and thirst takes place in the preoptic area. Hypertonic saline and isoproterenol may act on other thirst systems or directly on feeding systems to decrease food intake.     

Water intake during the development of renal hypertension (2K-1C) in mice

For both practical and methodological reasons, mice have been the most widely employed species for development of transgenic and gene knockin and knockout animals. However, basic behavioral and physiology control and regulatory mechanisms in mice are not well characterized. To broaden our understanding of the processes maintaining body fluid and blood pressure homeostasis in the mouse, the objectives of this study were to evaluate voluntary water, and sodium intakes during the development of renal hypertension and to examine the relationship between hypertension and the quantities of water and salt ingested. In male, C57BL/6J mice, two-kidney, one-clip renal hypertension (2K-1C) was induced, and water and 1.8% NaCl intakes were monitored for 2 weeks. At the end of this period, all animals received arterial catheters for direct recording of blood pressure. The mice that received renal artery clips were sorted into hypertensive (152+/-4 mm Hg) and normotensive (122+/-2 mm Hg) groups and were compared to control (117+/-4 mm Hg) animals that underwent a sham renal clipping procedure. Hypertensive 2K-1C animals had significantly elevated water intake compared to control animals. On most of the postsurgical days, the normotensive 2K-1C animals did not display increased water intake in comparison to the control group. No significant effect was detected for 1.8% saline intake between any of the pairs of groups. In summary, the reduction of blood flow to a single kidney in the 2K-1C model of renal hypertension induces high blood pressure accompanied by sustained hyperdipsia in the mouse.     

Influence of food and water deprivation on the behavior of the white rat foraging in a hostile environment

Rats were trained to feed 2 hr per day, the food offered being placed at 16 m from a warm refuge and the ambient temperature being - 15 degrees C. They were food deprived for 0, 12, 22, 46, 70 and 94 hr prior to the six feeding sessions. Speed of feeding and meal duration were not influenced by food deprivation. The amount eaten, the number of meals, the time spent at the feeder, the speed of running to the feeder and the number of foraging rats increased from 0 hr fast to 22 hr then plateaued for the 46, 70 and 96 hr fasts. The same experiment was carried out after water deprivation for 0, 12, 22, 46 and 70 hr. Rats could find, at -15 degrees C, water kept at 30-40 degrees C and at 16 m from their warm refuge. The speed of running to water and the rate of drinking were not influenced by water deprivation. The amount drunk, drinking-bout duration, the number of drinking-bouts, total drinking time and the number of rats drinking increased monotonically from 0 to 70 hr deprivation. Two main conclusions are drawn from these data: (1) in the rat, up to 70 hr deprivation, the motivation to feed seems to be stronger than the motivation to drink; (2) to satisfy hunger or thirst, the nervous system uses several different motor subsystems of behavior.     

Changes in myocardial pyrimidine nucleotide levels following repeated injections of isoproterenol in rats

Changes which might lead to the initiation of cardiac hypertrophy include possible variations in the dynamics of nucleotides. In the experiments reported in this paper, changes in the pool sizes of adenine, uracil and cytosine nucleotides were observed during the initial phase of cardiac overload.Repeated subcutaneous injections of isoproterenol (ISO) (5 mg·kg^–1 body weight, s.c.) were performed so as to produce symmetric cardiomegaly in rats. Under these conditions, the dry weight of the heart, on the fifth day of dialy injections of ISO, had increased by 43% and the RNA concentration by 39%. There was no significant change in the DNA concentration. No further changes in weight or in DNA and RNA concentrations were recorded from the fifth to the tenth day of treatment.Changes in UTP and ATP were carefully monitored during the first days following ISO application. The levels of both nucleotides decreased sharply at first. The ATP level remained below the control value for at least 48 h while the UTP level was rapidly restored and a further increase occurred resulting in a maximal enlargement of 82% after the 12th h. At the same time, the uracil nucleotide pool and the cytosine nucleotide pool had increased by 76% and 101%, respectively, while the adenine nucleotide content of the myocardium remained 15% below control level. Repeated injections of ISO induced effects on ATP and UTP levels which were similar in direction but attenuated.The significance of an increase in the pyrimidine nucleotide pools in relation to nucleic acid synthesis is discussed.     

Ontogenetic role of angiontensin-converting enzyme in rats: Thirst and sodium appetite evaluation

We investigated the influence of captopril (an angiotensin converting enzyme inhibitor) treatment during pregnancy and lactation period on hydromineral balance of the male adult offspring, particularly, concerning thirst and sodium appetite. We did not observe significant alterations in basal hydromineral (water intake, 0.3 M NaCl intake, volume and sodium urinary concentration) or cardiovascular parameters in adult male rats perinatally treated with captopril compared to controls. However, male offspring rats that perinatally exposed to captopril showed a significant attenuation in water intake induced by osmotic stimulation, extracellular dehydration and beta-adrenergic stimulation. Moreover, captopril treatment during perinatal period decreased the salt appetite induced by sodium depletion. This treatment also attenuated thirst and sodium appetite aroused during inhibition of peripheral angiotensin II generation raised by low concentration of captopril in the adult offspring. Interestingly, perinatal exposure to captopril did not alter water or salt intake induced by i.c.v. administration of angiotensin I or angiotensin II. These results showed that chronic inhibition of angiotensin converting enzyme during pregnancy and lactation modifies the regulation of induced thirst and sodium appetite in adulthood.     

苯肾上腺素预输注防治老年人脊麻后低血压的临床研究

目的 评估预防性输注苯肾上腺素用于防治老年人脊麻后低血压的疗效和安全性。方法 将2017年1月~4月在本院行骨科下肢手术且年龄超过60岁的52例患者,随机分为P组和C组,每组26例。两组患者均使用0.5%布比卡因2 ml进行腰麻,P组在腰麻注药后立即静脉给予苯肾上腺素（100 μg/ml）1 ml/min,C组给予生理盐水1 ml/min。观察两组患者的术中MAP、每例患者低血压、高血压、心动过缓的发作次数,发作低血压、高血压、心动过缓的患者数,初次低血压的发作时刻,术中最低和最高MAP,苯肾上腺素和液体的总使用量,术后6 h、24 h、48 h发生心电图改变的患者数以及肌钙蛋白增加的患者数。结果 P组MAP高于C组,初次低血压的发作时刻大于C组,差异有统计学意义（P＜0.05）。P组每例患者低血压的发作次数少于C组,差异有统计学意义（P＜0.05）。两组患者发生低血压的患者数、术中最低和最低MAP比较,差异无统计学意义（P＞0.05）。P组患者的无低血压发作的累计比例高于C组,差异有统计学意义（P＜0.05）。两组患者术中发生高血压和心动过缓例数、每例患者高血压和心动过缓的发作次数、术中液体总使用量比较,差异无统计学意义（P＞0.05）。P组的苯肾上腺素总使用量高于C组（P＜0.05）。两组患者在术后6 h、24 h均未发生心电图异常改变情况。P组患者在术后48 h内未发生心电图异常改变情况,C组有2例患者（7.69%）在术后48 h发生了心电图异常改变,两组差异无统计学意义（P＞0.05）。C组患者在术后6 h、24 h、48 h发生肌钙蛋白定量升高的患者数均高于P组,但差异无统计学意义（P＞0.05）。结论 预防性输注苯肾上腺素可有效防治老年人脊麻后低血压,减少低血压发作次数,延迟低血压发作时间,提高手术麻醉的安全性。     

PPARα和其配体在急性心肌缺血性损伤中的作用及机制初探

目的： 探讨过氧化物酶体增殖物激活受体α（PPARα）和其配体非诺贝特在急性心肌缺血性损伤中的作用及其机制。方法: 30只雄性纯系Wistar大鼠随机分为3组，每组10只：①正常对照组（control）；②异丙肾上腺素损伤组（Iso）采用腹腔内注射异丙基肾上腺素复制急性心肌缺血损伤的动物模型；③非诺贝特组（FF）在预先给予非诺贝特的基础上复制异丙基肾上腺素致急性心肌缺血损伤的动物模型。生化酶学方法测定大鼠血清心肌酶学(CK,LDH)；紫外分光光度法测定心肌组织中髓过氧化物酶（MPO）的酶活力；酶联免疫吸附实验（ELISA）测定血清中TNF-α的浓度； RT-PCR方法测定PPARα mRNA的表达水平。结果: Iso组血清心肌酶CK和LDH的含量和心肌组织中髓过氧化物酶（MPO）的酶活力显著高于对照组，心肌炎症反应较重，血清TNF-α浓度也增高，同时心肌组织中PPARα mRNA表达水平明显低于对照组； FF组与Iso组比较，前者血清心肌酶CK和LDH的释放受到抑制低于后者，心肌组织中髓过氧化物酶MPO的酶活力和血清TNF-α浓度均低于Iso组，但心肌组织中PPARα mRNA表达水平高于Iso组 （P＜0.01）。结论: PPARα参与急性心肌缺血性损伤中的炎症反应； PPARα配体非诺贝特可能是通过激活PPARα，减轻炎症反应，对缺血心肌具有保护作用。