Hypoventilation after acute phrenicotomy of the urethane anaesthetized rats.

The aim of this study was to explore the mechanism resulting in hypoventilation in rats with denervated diaphragm. Bilateral cervical phrenicotomy (PX) was performed in 15 male rats anaesthetized with urethane (1.3 g/kg i.p.); other 8 rats were sham operated (SX). Ventilation, PaCO2 and the integrated EMG of the external intercostal muscles (iEMG) were measured before and after the surgery, at regular intervals, up to 4 hours postoperatively. During the 4 hours after PX there was a progressive decrease in minute ventilation and an increase in PaCO2 compared with the control values and with that in the SX rats. The increase in PaCO2 was accompanied by an increase in the peak amplitude of the iEMG to 155 +/- 18% of control values after PX and to 228 +/- 33% 4 hours later. Despite the augmented EMG activity tidal volume gradually decreased. The iEMG of the intercostal muscles, however, did not reach a maximum because the shortlasting stimulation of breathing by acute hypercapnia and hypoxia as the result of added dead space (0.5 ml) increased the iEMG still further. These results indicate that both the central and peripheral mechanisms contribute to hypoventilation in anaesthetized rats with denervated diaphragm.     

Effect of pentobarbital and urethane on the release of hypothalamic somatostatin and pituitary growth hormone

Hypothalamic somatostatin release was investigated in the rat to elucidate the mechanism of anesthetic action on growth hormone (GH) release from the pituitary. Intraperitoneal injection of sodium pentobarbital (5 mg/100 gm B.W.) significantly elevated serum GH levels and increased hypothalamic somatostatin concentration from basal values of 0.98 +/- 0.01 to 1.21 +/- 0.06 ng/mg wet wt. In contrast, urethane (150 mg/100 gm B.W., IP) administration lowered serum GH levels and hypothalamic somatostatin concentration (0.64 +/- 0.04 ng/mg wet wt.). However, the mean concentration of pancreatic somatostatin showed no change in either case. In rats receiving passive immunization with 0.5 ml rabbit antiserum to somatostatin (SRIF-AS), serum GH levels were significantly increased (67.5 +/- 12.3 ng/ml) and did not differ from those in the group treated with normal rabbit serum (NRS) plus pentobarbital (101.3 +/- 18.5 ng/ml). However, serum GH levels in rats injected with SRIF-AS plus pentobarbital were increased to higher values than in rats given SRIF-AS alone. When urethane was administered to rats after passive immunization with SRIF-AS, urethane-induced suppression of serum GH levels was markedly inhibited (5.5 +/- 2.0 vs. 33.5 +/- 7.5 ng/ml). These results suggest a possibility that the changes in serum GH levels observed with pentobarbital or urethane administration may be induced at least in one part by somatostatin released from the hypothalamus.     

Effects of phrenicotomy and exercise on hypoxia-induced changes in phrenic motor output.

To investigate models of plasticity in respiratory motor output, we determined the effects of chronic unilateral phrenicotomy and/or exercise on time-dependent responses to episodic hypoxia in the contralateral phrenic nerve. Anesthetized (urethane), ventilated, and vagotomized rats were presented with three, 5-min episodes of isocapnic hypoxia (11% O(2)), separated by 5 min of hyperoxia (50% O(2)). Integrated phrenic (and hypoglossal) nerve discharge were recorded before and during each hypoxic episode, for the first 5 min after the first hypoxic episode, and at 30 and 60 min after the final episode. Of 36 rats, one-half were sedentary while the other one-half had free access to a running wheel; each of these groups was split into three subgroups: 1) unoperated, 2) chronic left phrenicotomy (27-37 days), and 3) sham operated. Neither unilateral phrenicotomy nor running wheel activity influenced the short-term hypoxic phrenic response (during hypoxia) or long-term facilitation (posthypoxia). Posthypoxia frequency decline was exaggerated in phrenicotomized-sedentary rats relative to unoperated-sedentary rats (change in burst frequency = -23+/-4 vs. -11 +/-5 bursts/min, respectively; 5 min posthypoxia; P<0.05), an effect that was eliminated by spontaneous exercise. The results indicate that neither voluntary running nor unilateral phrenicotomy has major effects on time-dependent hypoxic phrenic responses, with the exception of an unexpected effect of phrenicotomy on posthypoxia frequency decline in sedentary rats.     

Lung function in acute paraquat intoxication.

Functional and morphological examination of the lungs was performed in rats 48 hours after intratracheal injection of 0.5 mg/kg of the herbicide paraquat. Pronounced tachypnoea was observed (235+/-20 c/min), which also persisted under urethane anaesthesia (210+/-18 c/min). In control rats the mean breathing rate was 115+/-11 and 90+/-9 c/min in wake and anaesthetized rats respectively. The rate of breathing decreased to comparable values in experimental and control rats after bilateral cervical vagotomy. The functional residual lung capacity was significantly increased in experimental rats. After vagotomy also this increase of functional residual capacity became normalized. Histologically the disease was characterized by focal formation of hyaline membranes and oedema with occasional haemorrhages and signs of inflammation. The significant role fo vagal function in lung pathology is demonstrated.     

Pentobarbital inhibits the billiary excretion of organic acids: a study with succinysulfathiazole in the rat.

The present study was undertaken to determine whether the use of pentobarbital as an anesthetic reduces the biliary excretion of acidic drugs in rats. The drug chosen for the experiment was succinylsulfathiazole, a compound excreted unmetabolized in the bile. Animals anesthetized with urethane excreted 22.1% of the dose in the bile as compared to only 8.4% for the same time period in pentobarbital anesthetized animals. The choice of anesthetic did not affec the bile flow but did influence the bile/liver concentration gradient of succinylsulfathiazole, with the pentobarbital treated rats demonstrating a significantly lower value. Despite the higher biliary excretion of succinylsulfathiazole in the urethane treated rats, the total amount in the bile plus urine was 60% of the dose in the urethane anesthetized animals as compared with 62% in the pentobarbital treated rats. These results suggest that pentobarbital reduced the hepatic transport of succiylsulfathiazole into the bile. The question whether urethane is a preferred anesthetic for biliary excretion studies warrants further investigation.     

Effects of anesthesia on cystometry and leak point pressure of the female rat

Anesthetics operate by different mechanisms and are often used to perform urodynamics in animals. The objective of this study was to compare the effects of ketamine/xylazine and urethane anesthetics on filling, voiding, and leak point pressure (LPP) in female rats. Nineteen rats underwent awake cystometry 2 days after suprapubic bladder catheter implantation. Bladders were filled with saline (5 ml/hr), while bladder pressure was measured. Half the rats were then anesthetized with urethane i.p. and half were anesthetized with ketamine and xylazine i.p. (K/X). All rats then underwent cystometry and LPP testing under anesthesia. Spontaneous nonvoiding contractions were analyzed and capacity was determined by voiding or leakage. Capacity was significantly higher in awake rats (0.55 +/- 0.06 ml) than with either K/X (0.21 +/- 0.06 ml) or urethane (0.30 +/- 0.05 ml). The pressure just prior to voiding in awake cystometry (15.6 +/- 1.7 cm H2O) was not significantly different from that with either anesthetic (K/X: 10.1 +/- 1.0 cm H2O; urethane: 13.3 +/- 2.0 cm H2O). Spontaneous nonvoiding contractions occurred in 4 rats with urethane and 3 rats with K/X. The volume at which the first contraction occurred was significantly lower with K/X (0.05 +/- 0.02 ml) than urethane (0.19 +/- 0.04 ml). There was no significant difference in the frequency of spontaneous nonvoiding contractions between K/X (4.58 +/- 0.30/min) and urethane (5.16 +/- 2.66/min), nor was there a difference in LPP between anesthetics (K/X: 40.4 +/- 2.4 cm H2O; urethane: 36.2 +/- 3.9 cm H2O). The results suggest that urethane is preferable to K/X for anesthetized cystometry studies since it more closely simulates normal physiological responses.     

Sleep-time variation for ethanol and the hypnotic drugs tribromoethanol, urethane, pentobarbital, and propofol within outbred ICR mice.

To evaluate the phenotypic variation within a commercial outbred mouse stock, we examined sleep-time (or duration of loss of righting reflex) of outbred ICR mice after i.p. injection of ethanol (4.0 g/kg of body weight), urethane (1.3 g), tribromoethanol (250 mg), and pentobarbital (60 mg), and after i.v. injection of propofol (30 mg). We observed high-grade individual differences in sleep-time that ranged from 0 to 179 min, 83.1 +/- 4.3 (mean and SEM of 100 mice) for ethanol; 0 to 169 min, 64.5 +/- 3.1 for pentobarbital; 0 to 160 min, 36.6 +/- 3.6 for urethane; 0 to 120 min, 21.5 +/- 2.2 for tribromoethanol; and 3 to 20.5 min, 7.1 +/- 0.3 for propofol. This extensive phenotypic variance within the outbred stock was as great as the variation reported among inbred strains or selected lines, and the varied susceptibility within the colony was inherited by Jcl:ICR-derived inbred strains IAI, ICT, IPI, and IQI. The range of sleep-time variance for ethanol, pentobarbital, urethane, tribromoethanol, and propofol within four-way cross hybrid Jcl:MCH(ICR) mice was 86.6%, 63.3%, 124%, 61.0%, and 53.1% that of outbred Jcl:ICR mice, respectively. The present study indicates that phenotypic variance within an outbred Jcl:ICR stock was at high risk for susceptibility to the drugs that depress the central nervous system and that Jcl:ICR-derived inbreds may be an excellent source of animal models for studying the anesthesia gene.     

Evaluation of cutaneous modifications in seventy-seven growth hormone-deficient children

Cutaneous parameters such as dermal thickness, stiffness, elasticity, skin surface lipid and hydration were evaluated using noninvasive methods in 77 growth hormone-deficient (GHD) children before replacement therapy and in 70 non-GHD children. We showed that in GHD children, dermis was thinner (0.70 +/- 0.10 vs. 0.80 +/- 0.10 mm, p < 0.0001 for prepubertal children and 0.81 +/- 0.10 vs. 0.94 +/- 0.11 mm, p < 0.0001 for pubertal children), stiffer (178.5 +/- 57.3 vs. 113.09 +/- 37 kPa, p < 0.0001 for prepubertal children and 172.5 +/- 61.7 vs. 117.3 +/- 42.5 kPa for pubertal children, p < 0.001) and less elastic (0.44 +/- 0.09 vs. 0.39 +/- 0.06 (nonelasticity index), p < 0.01 for prepubertal children and 0.39 +/- 0.05 vs. 0.33 +/- 0.04, p < 0.001 for pubertal children) compared to controls. Fourteen GHD children were re-evaluated after 1 year of GH treatment: dermal thickness and skin stiffness were significantly improved (p < 0.001 and p < 0.05 respectively) while elasticity was not modified. During the same period, 11 controls did not show any significant cutaneous modification. IGF-1 values, but not IGFBP-3 values, correlated positively with dermal thickness in GHD children, before and after 1 year of GH treatment. To conclude, GHD children exhibited specific cutaneous modifications. In a subset of GHD children, we showed that these modifications were influenced by GH treatment. More extensive studies are needed to see if these changes correlated with other GH effects.     

Effect of injectable or inhalational anesthetics and of neuroleptic, neuroleptanalgesic, and sedative agents on tumor blood flow

Among other parameters, varying blood flow values may be responsible for tumor-to-tumor variabilities in the radiobiologically hypoxic cell fraction of experimental rodent tumors. To test whether changes in tumor blood flow may be caused by anesthetic agents often used in radiobiology, the effect of injectable and inhalational anesthetics and of neuroleptic, neuroleptanalgesic, and sedative agents on blood flow in subcutaneous DS-carcinosarcomas implanted in Sprague-Dawley rats has been investigated using the 85Kr clearance technique. In conscious rats, 20-100 min after animal instrumentation mean blood flow is 0.62 +/- 0.17 ml/g/min (mean +/- SD) in 0.75 +/- 0.15 g tumors at a mean arterial blood pressure of 125 +/- 12 mm Hg. In animals receiving thiobutabarbital, chloral hydrate, or methoxyflurane tumor blood flow is somewhat higher than that measured in conscious rats. Tumor blood flow in animals receiving etomidate, ketamine-xylazine, fentanyl-fluanisone, or urethane is significantly lower than that in the thiobutabarbital group and somewhat lower than in the conscious animals. Blood flow values observed with midazolam, ketamine-midazolam, fentanyl-droperidol, droperidol, diazepam, and pentobarbital are similar to those measured in conscious rats. Virtually no flow alterations with time are detectable in conscious rats and with most of the drugs used. In animals anesthetized with urethane or methoxyflurane, tumor blood flow increases and tumor vascular resistance diminishes slightly with time.     

Cardiovascular effects of cocaine in anesthetized and conscious rats

This study examined the cardiovascular and respiratory effects of cocaine and procaine in anesthetized and conscious rats. Intravenous cocaine (0.16-5 mg/Kg) elicited a rapid, dose dependent increase in mean arterial pressure of relatively short duration. In pentobarbital anesthetized (65 mg/Kg, i.p.) animals, the pressor phase was generally followed by a more prolonged depressor phase. These effects on arterial pressure were generally accompanied by a significant tachypnea and at larger doses (2.5 and 5 mg/Kg, i.v.), bradycardia. Procaine (0.31 and 1.25 mg/Kg, i.v.) produced similar cardiovascular and respiratory effects (depressor phase, tachypnea) in pentobarbital anesthetized animals. In conscious-restrained animals, both cocaine and procaine (1.25 mg/kg, i.v.) produced pressor responses. The subsequent depressor response was, however, absent in both cases. The cardiovascular effects of cocaine (0.25-1 mg/Kg, i.v.) in urethane anesthetized (1.25 g/Kg, i.p.) animals were essentially similar to those observed in conscious animals. Procaine (1mg/Kg) did not produce any significant cardiovascular effects in urethane anesthetized animals, but did elicit tachypnea. Reserpine pretreatment (10 mg/Kg, i.p.) did not significantly attenuate the pressor response in urethane anesthetized animals. Phentolamine pretreatment (3 mg/Kg, i.v.) did significantly antagonize the pressor effect in urethane anesthetized animals. These results suggest that: the depressor phase is likely due to a interaction between local anesthetic activity (cocaine and procaine) and barbiturate anesthesia, the cardiovascular effects of cocaine in conscious animals are more similar to those observed in urethane anesthetized rats than in pentobarbital anesthetized rats and the pressor effect in urethane anesthetized rats is apparently due to a reserpine resistant catecholaminergic mechanism.     

Influence of different anaesthetics on pro-inflammatory cytokine expression in rat spleen

We examined the effect of five anaesthetic drugs commonly used in laboratory animal research (tribromoethanol, ketamine/xylazine, chloral hydrate, pentobarbital, and urethane) on the expression of four pro-inflammatory cytokines. The anaesthetic agents were applied at dosages normally used for deep surgical anaesthesia. Semiquantitative image analysis of interleukin (IL)-1beta, IL-2, IL-6, and tumour necrosis factor alpha (TNFalpha) mRNA expression in the spleen of male Wistar rats 4 h after application of the anaesthetic drugs showed that these had moderate immunomodulatory effects. Ketamine/xylazine, chloral hydrate, and pentobarbital enhanced the basal expression of IL-1beta and IL-6 mRNA in rat spleen, while urethane reduced splenic IL-1beta mRNA expression. Tribromoethanol, ketamine/xylazine, and urethane reduced the basal TNFalpha mRNA levels, whereas TNFalpha mRNA expression was unaffected by chloral hydrate and by pentobarbital. The data demonstrate that these anaesthetics have slight, but significant, effects on the basal immune status of rats.     

Surface pH responses of muscles of different fiber-type composition to catecholamines

Catecholamines were infused intravenously for 45 min into pentobarbital sodium-anesthetized rabbits. Physiologically low-dose epinephrine (0.125 microgram . min-1 . kg-1) decreased medial gastrocnemius (MG) surface pH (SpH) 0.16 +/- 0.03 (SD) (P less than 0.001) to a low of 7.25 +/- 0.11 and soleus (S) SpH 0.09 +/- 0.04 (P less than 0.01) to a low of 7.33 +/- 0.08 without changing blood pressure significantly. Surface temperature measurements suggested a statistically insignificant small increase in local blood flow in both muscles. With 1.25 microgram . min-1 . kg-1 epinephrine, MG SpH decreased 0.22 +/- 0.05 (P less than 0.001) to a low of 7.17 +/- 0.06 and S SpH decreased 0.10 +/- 0.05 (P less than 0.02) to a low of 7.26 +/- 0.04. The MG SpH decrease exceeded the S SpH decrease in each experiment for both epinephrine infusion levels, and the incremental difference was significantly greater (P less than 0.02) with the higher dose, demonstrating a dose-response effect more pronounced for glycolytic compared with oxidative fibers. Norepinephrine infusions of 1.25 and 2.5 micrograms . min-1 . kg-1 did not change SpH of either muscle significantly, despite increases in blood pressure of 10 +/- 3 (P less than 0.002) and 19 +/- 10 mmHg (P less than 0.02), respectively.     

Alteration in the D-amino acid content of the rat pineal gland under anesthesia

Summary In a previous report (Hamase, K. et al., Biochim Biophys Acta 1134: 214–222 (1997)), we showed that the rat pineal gland contains D-leucine (D-Leu) as well as D-aspartic acid (D-Asp). In this communication we report alterations in the content of these D-amino acids during anesthesia. The D-Asp content was significantly increased from 2.8 to 5.0, 4.8 and 5.8 nmol/pineal gland by administration of ether, urethane and pentobarbital, respectively. In contrast, the D-Leu content was decreased by administration of urethane or pentobarbital. The D-Leu content decreased from 4.2 to 2.2 pmol/pineal gland 4 hours after administration of urethane, although the content remained unchanged until 1.5 hours after administration. The content of the L-enantiomers of these amino acids were not affected by anesthesia. The urethane-induced decrease in D-leucine content was almost completely suppressed by a-agonist, (-)-isoproterenol, whereas the agonist itself had no effect.     

Low-frequency respiratory mechanical impedance in the rat

A modified forced oscillatory technique was used to determine the respiratory mechanical impedances in anesthetized, paralyzed rats between 0.25 and 10 Hz. From the total respiratory (Zrs) and pulmonary impedance (ZL), measured with pseudorandom oscillations applied at the airway opening before and after thoracotomy, respectively, the chest wall impedance (ZW) was calculated as ZW = Zrs - ZL. The pulmonary (RL) and chest wall resistances were both markedly frequency dependent: between 0.25 and 2 Hz they contributed equally to the total resistance falling from 81.4 +/- 18.3 (SD) at 0.25 Hz to 27.1 +/- 1.7 kPa.l-1 X s at 2 Hz. The pulmonary compliance (CL) decreased mildly, from 2.78 +/- 0.44 at 0.25 Hz to 2.36 +/- 0.39 ml/kPa at 2 Hz, and then increased at higher frequencies, whereas the chest wall compliance declined monotonously from 4.19 +/- 0.88 at 0.25 Hz to 1.93 +/- 0.14 ml/kPa at 10 Hz. Although the frequency dependence of ZW can be interpreted on the basis of parallel inhomogeneities alone, the sharp fall in RL together with the relatively constant CL suggests that at low frequencies significant losses are imposed by the non-Newtonian resistive properties of the lung tissue.     

Diazepam and pentobarbital dependence in the rat

Diazepam (100–133 mg/kg/day), administered chronically through a gastric fistula, and pentobarbital (ca 692 mg/kg/day), administered chronically in food, were studied for their dependence producing properties in Sprague-Dawley female rats. The diazepam abstinence syndrome was apparent 10 to 20 hours after withdrawal, persisted for over 60 hours and consisted of poker tail, explosive awakenings, digging in sawdust, jerks, tremors, wet dog shakes, hostility, decreased food and water consumption and weight loss. The pentobarbital abstinence syndrome came on rapidly peaking within 10 hours and was largely over by 16 hours. The pentobarbital abstinence syndrome differed from diazepam's by the presence of grand mal, clonic and atypical convulsions. Diazepam completely and in a dose related way suppressed the diazepam abstinence syndrome. Similarly pentobarbital suppressed the pentobarbital abstinence syndrome. The signs which could be suppressed in a dose related manner were different for the diazepam and pentobarbital abstinence syndromes. Diazepam only partially suppressed the pentobarbital abstinence syndrome and pentobarbital only partially suppressed the diazepam abstinence syndrome. These data indicate that diazepam and pentobarbital produce different types of dependencies in the rat and are not equivalent in suppressing signs of abstinence.     

Anesthetic dependence of the inhibitory effect of neurotensin on pentagastrin-stimulated acid secretion in rats. A possible role for somatostatin.

The existence of possible local mediators of the inhibitory effect of neurotensin on gastric acid secretion has not been determined. We perfused rats intragastrically with warmed saline and stimulated acid secretion with intravenous pentagastrin, 32 micrograms/kg/hr, and found that anesthesia with pentobarbital resulted in marked inhibition of acid secretion by intravenous neurotensin; however, anesthesia with urethane prevented this inhibitory effect of neurotensin from occurring. In addition, we found a significant increase in somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion in pentobarbital-anesthetized rats. Neither neurotensin nor pentagastrin infusion modified gastric luminal somatostatin-like immunoreactivity after either pentobarbital or urethane, and rats anesthetized with urethane did not show an increase of somatostatin-like immunoreactivity in portal venous blood during neurotensin infusion. These results suggested that somatostatin-like immunoreactivity, released into the portal circulation, was necessary for exogenous neurotensin to inhibit pentagastrin-stimulated gastric acid secretion under these conditions in anesthetized rats.     

Comparative stability of physiological parameters during sustained anesthesia in rats

Rats were anesthetized with pentobarbital, pentobarbital and atropine, inactin [5-ethyl-5-(1'-methyl-propyl)-2-thiobarbiturate], ether and inactin, or urethane. Cardiovascular and arterial acid-base parameters were monitored over a 3-hour period of anesthesia. Heart rate, arterial pressures, and pH progressively decreased with duration of pentobarbital anesthesia. Changes observed in rats anesthetized with the thiobarbiturate, inactin, were similar although generally less severe. Most subjects treated with the barbiturates were markedly hypercapnic. Urethane anesthesia was characterized by a higher and more stable heart rate and greater pulse pressure. Arterial carbon dioxide and bicarbonate levels in the urethane group were substantially lower at all sampling times than the values obtained in the barbiturate groups.     

Effect of systemic hypoxia and reoxygenation on electrical stability of the rat myocardium: chronophysiological study

The aim of the study was to determine the dependence of changes in the electrical stability of the heart on the light-dark cycle (LD cycle) in disorders of pulmonary ventilation. The ventricular arrhythmia threshold (VAT) was measured in female Wistar rats (adaptation to the light regime 12:12 h, ketamine/xylazine anesthesia 100 mg/15 mg/kg, i.m., open chest experiments). The conditions of the normal artificial ventilation and reoxygenation were V(T) = 1 ml/100 g, respiratory rate 40 breaths/min, hypoventilation V(T) = 0.5 ml/100 g, respiratory rate 20 breaths/min. The animals (n=11 light group; n=19 dark group) were subjected to 20 min hypoventilation followed by 20 min reoxygenation. The control prehypoventilatory VAT differences were not found between the light (1.90+/-0.84 mA) and dark (1.88+/-0.87 mA) part of the day. Artificial hypoventilation changed the VAT values in light and dark part of the day differently. While during the light period, the average VAT values in most animals (90.9 %) were significantly decreased (1.29+/-0.59 vs. 1.90+/-0.84 mA control, p<0.05), during the dark part these values showed either significant increase (63.2 %) (2.23+/-0.77 vs. 1.48+/-0.39 mA, p<0.005) or a slight non-significant decrease (36.8 %) (2.18+/-0.89 vs. 2.54+/-0.99 mA). Reoxygenation returned the VAT values to the level before hypoventilation by an increase of the VAT (81.8 %) in the light part of day and by decrease of the VAT (68.4 %) in the dark part of the day. It is concluded that 1) in hypoventilation/reoxygenation model, the significant higher average VAT values are in the dark part of the day vs. the light one, 2) rat hearts are more resistant to systemic hypoxia and reoxygenation in the dark part of day, and 3) proarrhythmogenic effect of the systemic hypoxia is only seen in the light part of the day.     

内皮素对麻醉大鼠动脉压力感受器反射的调制作用

在27只隔离灌流颈动脉窦区的麻醉大鼠,观察了内皮素（ET-1）对动脉压力感受器反射的调制作用。结果如下：（1）在颈动脉窦区灌流1nmol／L的ET-1时,压力感受器机能曲线向左下方移位,曲线的最大斜率（PS）由0.40±0.02增至0.51±0.02kPa／kPa（P＜0.01）,压力感受器反射性血压下降幅度（RD）由5.66±0.23增至6.76±0.22kPa（P＜0.01）。由此提示,这一剂量的FT-1对压力感受器反射有易化作用。（2）用10nmol／L的ET-1灌流时,压力感受器机能曲线则向右上方移位,PS降至0.28±0.01kPa／kPa（P＜0.01）,RD降至4．16±0.19kPa（P＜0.01）;100nmol／L的ET-1可使压力感受器机能曲线向右上方移位更为明显,PS降至0.19±0.03kPa（P＜0.001）,RD进一步降至3.33±0.38kPa（P＜0.001）。这些结果表明,上述两种剂量的ET-1对压力感受器反射有抑制作用。（3）ETA受体选择性阻断剂BQ123（0.15μmol／L）可以阻断ET-1（10nmol／L）对压力感受器反射的抑制效应。（4）预先灌流KATP通道阻断剂格列苯脲（10μmol／L）,也可阻断ET-1的效应。综上所述,ET-1对压力感受器反射有双重效应,低剂量时有易化作用,而较高剂量时则有抑制作用,后一作用由ET-1型受体介导并有KATP通道的参与。     

Carotid body excision significantly changes ventilatory control in awake rats

We determined the effects of carotid body excision (CBX) on eupneic ventilation and the ventilatory responses to acute hypoxia, hyperoxia, and chronic hypoxia in unanesthetized rats. Arterial PCO2 (PaCO2) and calculated minute alveolar ventilation to minute metabolic CO2 production (VA/VCO2) ratio were used to determine the ventilatory responses. The effects of CBX and sham operation were compared with intact controls (PaCO2 = 40.0 +/- 0.1 Torr, mean +/- 95% confidence limits, and VA/VCO2 = 21.6 +/- 0.1). CBX rats showed 1) chronic hypoventilation with respiratory acidosis, which was maintained for at least 75 days after surgery (PaCO2 = 48.4 +/- 1.1 Torr and VA/VCO2 = 17.9 +/- 0.4), 2) hyperventilation in response to acute hyperoxia vs. hypoventilation in intact rats, 3) an attenuated increase in VA/VCO2 in acute hypoxemia (arterial PO2 approximately equal to 49 Torr), which was 31% of the 8.7 +/- 0.3 increase in VA/VCO2 observed in control rats, 4) no ventilatory acclimatization between 1 and 24 h hypoxia, whereas intact rats had a further 7.5 +/- 1.5 increase in VA/VCO2, 5) a decreased PaCO2 upon acute restoration of normoxia after 24 h hypoxia in contrast to an increased PaCO2 in controls. We conclude that in rats carotid body chemoreceptors are essential to maintain normal eupneic ventilation and to the process of ventilatory acclimatization to chronic hypoxia.