First Group Of Rats Research Articles

Involvement of bombesin in spermine-induced corticosterone secretion and intestinal maturation in suckling rats.

In this study we investigated whether brain-gut peptides are implicated in the activation of the hypophysial-adrenal axis (HAA) in suckling rats treated orally with spermine. The first group of rats received i.p. injections of bombesin, vasoactive intestinal polypeptide (VIP), somatostatin or neurotensin, starting on day 11 of life, and killed on day 14. The small intestine was removed and analysed for its content of proteins, DNA, polyamines and for its specific activity (SA) of disaccharidases. The second group of rats received one of the hormones cited above and was killed 45 min after the treatment for determination of corticosterone plasma concentration. Rats of the third group were adrenalectomised then treated with bombesin as the first group. The fourth group of rats was orally treated with spermine and sacrificed 2, 3, 4, 6 and 8 h thereafter for analysis of plasma and intestinal concentrations of bombesin. The i.p. injection of bombesin increased the sucrase and maltase SA in the whole small intestine, while it decreased the lactase SA in the distal part. Intestinal weight and length, contents of DNA, protein, spermidine and spermine, and corticosterone plasma levels were enhanced by bombesin treatment. Somatostatin, neurotensin and VIP were ineffective on all the parameters studied. Adrenalectomy, in bombesin-treated rats, decreased the sucrase and maltase SA in the whole intestine, and decreased the lactase SA in the proximal intestine. It has no effect on intestinal weight and length, and protein content. Oral administration of spermine had no effect on plasma concentration of bombesin, whereas it decreased the content of this peptide in the whole small intestine. It is possible that bombesin may control intestinal development in suckling rats and be a link between the ingestion of spermine and the liberation of corticosterone by the adrenal glands.

BENEFICIAL EFFECTS OF PENTOXIFYLLINE ON CYCLOSPORINE‐ INDUCED NEPHROTOXICITY

1. Hypertension and renal failure are the two most common and severe complications due to cyclosporine A (CsA) therapy after transplantation. To determine whether an in vivo treatment with pentoxifylline (PTX) can prevent the toxic effects of CsA, three groups of rats were studied. 2. The first group of rats (n = 11) received daily injections of CsA (15 mg/kg, i.m.) and PTX (45 mg/kg, i.p., b.i.d.), the second group of rats (n = 11) was treated with CsA only and the third group of rats (n = 11) served as the control group (vehicle treatment). 3. Whole blood CsA levels were similar in CsA + PTX and CsA alone groups. Although CsA treatment significantly increased mean arterial blood pressure (110.00 +/- 2.48 mmHg; P < 0.01), there was no significant increase in the PTX co-treated group (104.09 +/- 2.96 mmHg) compared with initial values. In both the CsA alone and CsA + PTX groups the heart rate (365.45 +/- 6.65 and 357.27 +/- 7.23 b.p.m., respectively; P < 0.05) were found to be significantly higher than initial values. Serum creatinine levels increased significantly in the CsA alone group (1.40 +/- 0.11 mg/dL; P < 0.01) compared with control values (0.81 +/- 0.04 mg/dL). This increase was prevented by co-treatment with PTX (serum creatinine 1.11 +/- 0.01 mg/dL; P < 0.05). Total [99mTc]-DTPA percentage renal uptake, as an index of glomerular filtration rate (GFR), was markedly and significantly lower in the CsA alone group (10.01 +/- 0.79%; P < 0.01) than in the control group (18.19 +/- 1.32%). Pentoxifylline co-treatment attenuated this decrease compared with GFR in the CsA alone group (13.00 +/- 0.75%; P < 0.01). 4. These results suggest that the co-administration of PTX with CsA may prevent the dose-limiting toxic effects of CsA therapy.

Cyclin and cyclin-dependent kinase expression in the remnant glomerulus.

Recent studies suggest that subtotal renal ablation is associated with an early phase of mesangial cell proliferation. Because the mechanism(s) responsible for this response have not been elucidated, the study presented here sought to determine if changes in expression of positive cell cycle regulators, including pRb, cyclin E, and cdk2, occurred in the glomerulus during the early period of compensatory renal hypertrophy that follows 5/6 renal ablation. A first group of rats underwent sham operation and served as the control group. A second group of rats underwent 5/6 renal ablation. Ninety-six hours after subtotal ablation, protein was extracted from sieved glomeruli for Western blot analysis of proliferating cell nuclear antigen (PCNA) and retinoblastoma protein expression (pRb). RNA was extracted from sieved glomeruli for Northern blot analysis of cyclin E and cdk2 mRNA levels, and renal cortical tissue was subjected to immunohistochemical analysis of PCNA. On average, one PCNA-positive nucleus was present every 22 glomerular profiles in normal rats. The number of PCNA-positive nuclei increased fivefold in glomeruli, 96 h after renal ablation (P < 0.05). pRb was present only in the unphosphorylated state in normal glomeruli, but the increase in PCNA was accompanied by the appearance of phosphorylated pRb in remnant glomeruli. mRNA levels for cyclin E increased twofold in remnant glomeruli, whereas mRNA levels for cdk2 were unchanged. It was concluded that renal ablation leads to cell cycle progression in the glomerulus and an increase in the G1 cyclin, cyclin E, is associated with the appearance of phosphorylated retinoblastoma protein.

Ro 15-4513 selectively attenuates ethanol, but not sucrose, reinforced responding in a concurrent access procedure; comparison to other drugs.

The experiments described in this report used a concurrent access procedure to study ethanol reinforcement. Rats were trained to lever press for a 10% sucrose solution and a 10% ethanol/10% sucrose mixture, and both reinforcers were available on variable-interval 5-s schedules. In baseline and vehicle injection sessions, the animals distributed their responding between both solutions. When injected with the partial inverse benzodiazepine agonist Ro 15-4513 (3, 9, and 18 mg/kg), responding for the ethanol solution decreased while responding for sucrose remained intact. Ethanol injections (0.5 and 1.0 g/kg) engendered a similar profile. Chlordiazepoxide led to an increase in ethanol mix responding at 2 mg/kg and a decrease in ethanol mix responding at higher doses; no dose affected sucrose responding. Morphine (0.5-16 mg/kg) decreased responding for both the ethanol mix and sucrose solutions, more or less simultaneously. Naloxone (0.125-20 mg/kg) selectively reduced ethanol mix responding at low doses, and decreased responding for both reinforcers at high doses. In another group of animals, isocaloric alternatives were concurrently available: 10% ethanol/0.25% saccharin versus 14% sucrose. Injections of Ro 15-4513 and chloridiazepoxide produced similar results as in the first group of rats: an increase in ethanol mix responding with low dose chlordizepoxide, and a decrease in ethanol mix responding with Ro 15-4513. However, naloxone injections did not selectively affect responding for either of the reinforcers when they were isocaloric. These results are discussed in terms of ethanol's neuropharmacological actions.

Neural regulation of the enhanced uptake of glucose in skeletal muscle after endotoxin.

Previous studies have demonstrated that in vivo injection of lipopolysaccharide (LPS) acutely stimulates glucose uptake (GU) in skeletal muscle. The purpose of the present study was to determine whether this enhanced GU is neurally mediated. In the first group of rats, a unilateral sciatic nerve transection was performed 3 h before injection of LPS, and in vivo GU was assessed using 2-[14C]deoxy-D-glucose 40 min after LPS injection. At this time, LPS-treated rats were hyperglycemic (12 mM), and insulin levels were not different from control rats. In the innervated leg, LPS increased GU 43-228%, depending on the muscle type. In contrast, LPS failed to increase GU in muscles from the denervated limb. In other experiments, somatostatin was infused to produce an insulinopenic condition before the injection of LPS. Despite insulinopenia, muscle GU was still increased by LPS. In control rats, in which the euglycemic hyperinsulinemic clamp technique was used, acute muscle denervation was shown to impair insulin-mediated GU in the presence of pharmacological, but not physiological, insulin levels. Non-insulin-mediated GU (NIMGU) was assessed in rats that were insulinopenic and hyperglycemic. In innervated muscle, NIMGU was increased 56-126 and 118-145% when the plasma glucose was elevated to 9 and 12 mM, respectively. In contrast, hyperglycemia-induced increases in NIMGU were attenuated in denervated muscle. These data demonstrate that 1) the early LPS-induced stimulation of muscle GU is mediated via a non-insulin-mediated pathway and 2) the LPS-induced increase in NIMGU in muscle is neurally mediated.

984-28 Vitamin E does not Improve Regenerated Endothelium Dysfunction Following Balloon-induced Vascular Injury

Fibromuscular intimal injury is frequent after coronary angioplasty. Peroxidation of circulating and membrane lipids have been implicated in intimal hyperplasia and endothelial dysfunction following arterial trauma. The aim of this study was to evaluate the effects of the natural membrane antioxidant vitamin E on the regenerated endothelium dysfunction. A first group of rats (n = 10) was pretreated with vitamin E (VE) 100 IU/kg/day for a week before undergoing aortic (thoracic) endothelial denudation with a Fogarty catheter. Rats were then fed with the same VE supplemented diet for a period of 2 months. A second group (n = 10) was similarly denuded and fed with soya oil (SO), VE vehicle, for the same period. A third group (n = 10) was denuded (DN) without any treatment and a fourth group was used as control (CL) without denudation. Endothelial-dependent and independent relaxation were assessed in organ chambers with acetylcholine (ACH 10 -9 –10 -4 mol/L) and sodium nitroprusside (SNP 10 -9 –10 -4 mol/L) respectively. Endothelial regeneratin was evaluated with Evan's blue staining. Vascular relaxation to SNP was not affected either by the regeneration process or the VE supplementation. However, endothelial-dependent relaxation to ACH was significantly impeded in the regenerated endothelium compared to control(p &lt; 0.01) and was not influenced by the VE or the SO (p = NS) [ED 50 (–logM); CL:6.8 ± 0.1, DN:6.3 ± 0.1, VE:6.0 ± 0.2,SO: 6.1 ± 0.1, ANOVA]. Morphometric studies with Evan's blue staining showed over 95% regeneration of the endothelial surface of the denuded aortas. Our present results suggest that in spite of a complete anatomical regeneration. endothelial cells do not resume predenudation function. Endothelial-independent relaxation was preserved in all groups indicating that smooth muscle function was not altered by the regenerating process. The presence of dietary supplement of VE (up to 20-fold the dietary requirement) did not improve the endothelial dysfunction in the endothelium-regenerated rat aorta model.

Evaluation of an allogeneic cultured dermal substitute composed of fibroblasts within a spongy collagen matrix as a wound dressing.

The purpose of this study was to examine whether epithelialisation is promoted when an allogeneic cultured dermal substitute is used as a biological wound dressing. The dermal substitute was prepared by plating fibroblasts on to a spongy collagen matrix, and then culturing them for 7 to 10 days. A new animal wound model was designed to measure re-epithelialisation quantitatively. A full thickness skin defect was made on the dorsum of each of 33 rats; the skin was excised, leaving a layer of pannicular carnosus with an island of intact skin in the central portion of the skin defect. In the first group of rats (n = 13), a piece of cultured dermal substitute was applied to the wound, and a medicated covering material was placed over it. Re-epithelialisation from the island of intact skin was monitored over a period of 7 days. In the second group of rats (n = 10), the wound was covered with an acellular collagen matrix in conjunction with the medicated covering material, and in the third group of rats (n = 10), the wound was covered with the medicated covering material alone. Both the macroscopic and histological findings indicated that the epithelial migration of the first group of rats was far more rapid than that in the other two groups. It comes to the conclusion that the application of this new fibroblastic cultured dermal substitute provided a good environment for the promotion of wound healing.

Phosphaturic effect of parathyroid hormone in the spontaneously hypertensive rat

The Okamoto spontaneously hypertensive rat (SHR) has been reported to have altered phosphate metabolism. Hypophosphaturia in the presence of increased serum parathyroid hormone (PTH) levels has been reported in the SHR. Therefore it has been postulated that the SHR may be hyporesponsive to the phosphaturic effect of endogenous PTH. In addition, the SHR exhibits enhanced renal sympathetic nerve activity. Recent studies demonstrated that stimulation of the renal adrenoreceptors decreases the phosphaturic response to PTH infusion. Thus a hyporesponsiveness to PTH in the SHR may be due in part to higher renal sympathetic tone. The present study determined the phosphaturic effect of a pharmacological dose of PTH (33 U/kg bolus and 1 U.kg-1.min-1 infusion) in the thyroparathyroidectomized SHR compared with its normotensive control, the Wistar Kyoto (WKY) rat. Three groups of clearance experiments were performed on male 10- to 14-wk-old SHR and WKY rats. In the first group of rats, the fractional excretion of phosphate (FEPi) in response to PTH infusion was 35.4 +/- 4.2% in the SHR (n = 6) and 26.2 +/- 3.0% in the WKY rat (n = 6), NS. In the second group, all animals underwent acute unilateral renal denervation (DNX). The FEPi in response to PTH was 35.3 +/- 1.5% in the innervated (INN) kidney of the SHR (n = 10) compared with 27.9 +/- 2.5% in the INN kidney of the WKY rat (n = 11), and 39.1 +/- 1.9% in the DNX kidney of the SHR compared with 30.5 +/- 2.0% in the DNX kidney of the WKY rat.(ABSTRACT TRUNCATED AT 250 WORDS)

Immediate-early genes in spontaneous wakefulness and sleep: expression of c-fos and NGFI-A mRNA and protein.

We have recently shown that the expression of two immediate-early genes, c-fos and NGFI-A, is strongly affected by sleep deprivation, In this work, we investigated c-fos and NGFI-A expression after periods of spontaneous wakefulness or sleep. We used in situ hybridization and immunocytochemistry to detect the corresponding mRNA and protein levels, respectively. A first group of rats (S-L) was sacrificed during the light hours at the end of a long period of sleep. A second group (W-L) was sacrificed under similar conditions, except that during the last half hour the animals had been spontaneously awake. A third group (W-D) was sacrificed during the dark hours after a long period of continuous wakefulness. We found that c-fos and NGFI-A expression in several brain areas was increased in W-L and W-D rats with respect to S-L rats. Some of these areas, including the cerebral cortex, basal ganglia, and colliculi, may have been activated by the increased sensory and motor activity associated with waking. The activation of other areas, such as the medial preoptic area of the hypothalamus and some brainstem nuclei, may be more directly related to sleep regulation. These results indicate that many regions showing an increased expression of immediate early genes after wakefulness induced by sleep deprivation are also activated by periods of spontaneous wakefulness.

Long-term cardiovascular role of nitric oxide in conscious rats.

The goal of this study was to determine the arterial pressure and renal excretory responses to a continuous intravenous infusion of 7.4 nmol/kg per minute of the nitric oxide synthesis inhibitor NG-nitro-L-arginine methyl ester (L-NAME) in conscious rats. Studies were conducted in six groups of Sprague-Dawley rats with indwelling arterial and venous catheters over periods lasting 12 to 26 days. In the first group of rats, L-NAME infusion for 9 days caused a sustained increase in arterial pressure, and on the ninth day arterial pressure was increased 29 mm Hg. Infusion of L-NAME at the higher dose of 37 nmol/kg per minute for 9 days caused no greater increase in arterial pressure than the lower dose. Sodium and volume balances and phenylephrine pressor sensitivity were unchanged during L-NAME administration at 7.4 nmol/kg per minute; plasma renin activity increased 2.5-fold, but the vasodepressor and vasodilator responses to acetylcholine and bradykinin were unchanged. Arterial pressure remained significantly increased 7 days after L-NAME was stopped, but in another group of rats, intravenous L-arginine infusion caused arterial pressure to return to control within 1 day. This same dose of L-arginine was administered for 7 days intravenously, and neither arterial pressure nor sodium balance changed. In other groups of rats, L-arginine was administered in conjunction with L-NAME; this prevented any change in arterial pressure, whereas D-arginine did not. In conclusion, the data suggest that continuous intravenous infusion of L-NAME causes sustained increases in arterial pressure in conscious rats without any sodium or water retention. The hypertension is accompanied by increases in plasma renin activity and can be prevented with intravenous L-arginine administration.

Influence of Calcium on Vascular Reactivity in Pregnant Rats

Objective: The fundamental aim of the study was to test whether calcium has some influence on vascular reactivity (VR) during pregnancy.Methods: In three groups of pregnant Wistar rats, VR was studied in isolated organs (aorta), using noradrenaline as a pressor agent. The first group of rats was placed on a normal diet; the second, on a low-calcium diet; and the third, on a high-calcium diet. The concentration of noradrenaline required to produce a determined contractile response in the vessel was measured (effective concentration = EC50) with VR being deduced from that: the stronger the EC, the weaker the VR and vice versa.Results: In rats on a low-calcium diet the EC50 was significantly higher than in those on a normal diet and a high-calcium diet.Conclusions: In rats on a low-calcium diet VR increased significantly from the second week of gestation, compared to rats on normal or high-calcium diet.

Linear-quadratic model underestimates sparing effect of small doses per fraction in rat spinal cord

The application of the linear-quadratic (LQ) model to describe iso-effective fractionation schedules for dose fraction sizes less than 2 Gy has been controversial. This paper describes experiments in which the effect of daily fractionated irradiation given with a wide range of fraction sizes was assessed in rat cervical spinal cord. The first group of rats were given doses in 1, 2, 4, 8 and 40 daily fractions. The second group of animals received three initial “top-up” doses of 9 Gy given once daily, representing three-quarters of tolerance, followed by doses in 1, 2, 10, 20, 30 and 40 daily fractions. The fractionated portion of the irradiation schedule therefore constituted only the final quarter of the tolerance dose. The endpoint of the experiments was paralysis of the forelimbs secondary to white matter necrosis. Direct analysis of data from experiments with full course fractionation up to 40 daily fractions (25.0–1.98 Gy per fraction) indicated consistency with the LQ model yielding an α/β value of 2.41 Gy. Analysis of data from experiments in which the three “top-up” doses were followed by up to 10 fractions (10.0–1.64 Gy per fraction) gave an α/β value of 3.41 Gy. However, data from “top-up” experiments with 20, 30 and 40 fraction (1.60–0.55 Gy per fraction) were inconsistent with the LQ model and gave a very small α/β value of 0.48 Gy. It is concluded that the LQ model based on data from large doses per fraction underestimates the sparing effect of small doses per fraction provided sufficient time is allowed between each fraction for repair of sublethal damage.

The effect of epidermal growth factor on liver lipid peroxidation and glutathione levels in lobectomized rats.

Epidermal growth factor (EGF) is a growth-promoting polypeptide which is found in highest levels in male mice in the submaxillary gland. It may also be a key factor in regeneration of the liver. We performed experiments with 18 male Wistar rats, divided into three groups. Hepatic left lobectomy (%30) was performed on the first group of rats. This group received an intraperitoneal injection of EGF for 7 days. The second group was the control group into which normal saline was injected for 7 days. The third group was sham-operated. On days 5 and 7 tomographic studies of liver were performed. On day 7 EGF levels, lipid peroxidation, and glutathione in liver were measured in all of the rats. While serum EGF levels did not show any significant change, the levels of lipid peroxide were decreased and glutathione was increased. Tomographic measurements indicated that administration of EGF increased the amount of regeneration.

Aluminium Hydroxide Uptake in the Stomach and in the Intestine of the Rat: A Histochemical Study

Using the histochemical stains aluminon, solochrome azurine and solochrome cyanine, intracellular binding of aluminium was examined in the mucosa of the stomach, duodenum, jejunum and ileum of adult rats. A first group of rats (n = 42) was sacrificed 1, 3, 6, 12, 24, 48 and 96 h after a single (300 mg x kg-1) oral administration of aluminium hydroxide. A second group of animals (n = 30) received daily the same dose of Al(OH)3 and was euthanatized after 3, 4, 5, 6 and 7 days of treatment. Aluminium deposits occurred only in the antral glands of the stomach and in rats treated for at least 3 days. The reactive deposits are located in the cytoplasm of the upper glandular cells and in the lumen of the antral glands. These results suggest that aluminium is absorbed through the antral mucosa and may be re-excreted through the glandular mucus flow into the digestive lumen where it will be absorbed again. We hypothesize that the metal could act as a delayed-effect drug.

Effect of fluid and salt supplements in preventing the development of “osteopenia” in hypokinetic rats

It has been suggested that a daily intake of fluid and salt supplements may be used to prevent bone demineralization in human subjects after prolonged exposure to hypokinesia (diminished muscular activity). Thus, the objective of this investigation was to evaluate the effect of fluid and salt supplementation in the prevention of development of osteoporosis in 64 Wistar rats with an initial body weight of 339–345 g, after exposure to 90 days of hypokinesia. They divided into 4 equal groups: the first group of rats placed under ordinary vivarium conditions and served as vivarium control; the second group were also placed under ordinary vivarium conditions but received daily fluid and salt supplements; the third group were subjected to pure hypokinesia, i.e. without the use of any preventive measures; and the fourth group were submitted to hypokinesia and received daily fluid and salt supplements. For the simulation of the hypokinetic effect the experimental group of rats were kept in small, individual, wooden cages. Through the experimental period the second and fourth group of rats received 8 ml/100 g body wt water and 5 ml 100 g body wt NaCl daily. By the end of the experimental period the animals were decapitated and the spongy matter of tibia and vertebrae of the rats were examined for changes referable to osteoporosis. It was found that the daily intake of fluid and salt supplements caused an increase in the volume density of primary spongiosa of bones. It was concluded that a daily intake of fluid and salt supplements may be used to prevent the development of osteoporosis in rats subjected to prolonged motor activity restriction.

Atrial natriuretic factor gene expression in rat ventricle during experimental hypertension

Activation of atrial natriuretic factor (ANF) gene expression has been reported in the rat ventricle in several models of hemodynamic overload, including hypertension. However, nothing is known about the potential trigger(s) and the time course of this activation during the development of hypertension. We measured aortic blood pressure, left ventricular hypertrophy (LVH), and left ventricular ANF mRNA concentration (LV ANF mRNA) in a first group of rats (study A) killed at 5 and 18 h and 2, 4, 6, 9, 15, and 30 days after suprarenal coarctation of the abdominal aorta. Coarctation induced a progressive rise in aortic blood pressure and left ventricular mass. We observed a biphasic accumulation of ANF mRNA in the left ventricle with a peak at day 4 averaging 20 times the control value long before stable hypertension and hypertrophy were achieved, followed by a decrease until day 9. This decrease was followed by a new rise, which stabilized around 10 times the control value seen during stable hypertension and hypertrophy. In a second group of rats killed at days 4 and 30 (study B), we determined, in addition to the previous parameters, left ventricular end-diastolic pressure (LVEDP), plasma renin (PRC), and plasma ANF concentrations. LVEDP and PRC were markedly increased at day 4, but at day 30, during stable hypertension and hypertrophy, these parameters returned to control values, whereas plasma ANF was increased. Using immunocytochemistry, we looked in a third group of rats (study C) for the presence of the immunoreactive peptide at days 4 and 30.(ABSTRACT TRUNCATED AT 250 WORDS)

Effect of marginal zinc deficiency on lipoprotein lipase activities in postheparin plasma, skeletal muscle and adipose tissues in the rat.

The activities of lipoprotein lipase in postheparin plasma, retroperitoneal adipose and gastrocnemius muscle tissues were determined in the rats fed 2.8 ppm of dietary zinc for eight weeks, as compared with pair-fed and ad libitum-fed rats given 30.8 ppm of zinc. The postheparin lipoprotein lipase activity, as determined by using a lipid emulsion labeled with [3H]triolein as the substrate, was significantly lower in the first group of rats, relative to that in the second and third groups. Tissue lipoprotein lipase activities were compared using the lipid emulsion and activator serum obtained from the zinc-deficient rats and the ad libitum-fed rats. The activator sera were devoid of very low density and low density lipoproteins, but enriched in high density lipoproteins. Muscle lipoprotein lipase activities were significantly lower when assayed with the activator serum from the zinc-deficient compared with the activities determined with the activator serum from the ad libitum-fed. Similarly, muscle lipoprotein lipase activities were lower in all groups when [3H]-triolein-labeled chylomicrons from the zinc-deficient were used as the substrate, compared with the activities determined using the chylomicrons from the ad libitum-fed. Lipoprotein lipase activities in the adipose tissues were not affected by the different sources of the activator sera and chylomicrons. The results strongly suggest that the decrease in postheparin lipoprotein lipase activity in zinc deficiency is not due to changes in tissue lipoprotein lipase enzyme per se, but to compositional alterations in chylomicrons and high density lipoprotein, particularly, with regard to C apolipoproteins, modulators of lipoprotein lipase activity.

Naloxone and haemorrhagic hypotension in rats. Evidence against sympathetic nervous system as the primary mediator of improved cardiovascular haemodynamics.

Release of endogenous opiate-like substances seem to occur in different forms of stress. Earlier studies have shown that the opiate antagonist, naloxone, has a positive effect on cardiac performance and blood pressure in animals with haemorrhagic shock. In the present study, we have examined the involvement of the sympathetic nervous system in this response. Two groups of anaesthetized normotensive Wistar-Kyoto rats were studied. Both groups were bled rapidly (about 5 min) down to an arterial pressure of 50 mmHg and were kept at that level for 30 min. At the end of the 30-min bleeding period, naloxone 1, 2, or 5 mg kg-1 was injected i.v. in a small volume of saline. In the first group of rats (n = 6), the aortic pressure was kept constant at 50 mmHg by further bleedings after naloxone. In the other group (n = 7), the arterial pressure was allowed to rise after naloxone. As reported earlier, haemorrhagic hypotension caused a pronounced inhibition of renal sympathetic nerve activity. Naloxone injected after 30 min of hypotension caused an immediate rise in blood pressure, followed 1-2 min later by a rise in sympathetic nerve activity (SNA). In animals in which pressure was held constant by further bleeding after naloxone, only small and insignificant changes in SNA were observed. The conclusions are the following: injection of naloxone increases blood pressure in rats exposed to severe haemorrhage (Faden & Holiday 1979). The rise in aortic pressure is followed 1-2 min later by a rise in SNA.(ABSTRACT TRUNCATED AT 250 WORDS)

On the recovery of the electroretinogram of rats after removal of intravitreal lead particles.

Lead particles (1.4 mm2) were implanted into the vitreous body of rats (16 animals) for 10 days and the recovery rate of the ERG was measured over an observation time of 190 days. After extraction of the lead particles the a- and b-wave amplitudes show a recovery from about 60% to 87% in comparison to those of the intact fellow eyes between the 60th and 90th day of observation. In earlier experiments the mechanical damage was measured using glass splinters. The differences between these values and the above mentioned recovery rate after lead extraction correspond to the irreversible component of the metal intoxication. In another group of rats (16 animals) the lead particle was not removed before the end of the observation time of 190 days. Subtracting these ERG values from those of the first group of rats after lead extraction one gets small differences which correspond to the reversible component of the metal intoxication. The irreversible lead intoxication is much less than that of intravitreal iron particles as we found under the same conditions. The lead particles we used, are larger than those we have to handle in clinical cases taking the relation of surface area size of the particle to the total bulbus weight. The ophthalmoscopical findings are described.

Decreased serum triiodothyronine in starving rats is due primarily to diminished thyroidal secretion of thyroxine.

Although thyroxine (T4) 5'-deiodinase activity is diminished in liver homogenates of starved rats, no information is available regarding the effect of starvation on net T4 to triiodothyronine (T3) conversion in the intact rat. It appeared important to clarify this relationship since rat liver homogenates are widely used as a model for the study of the factors responsible for reduced circulating T3 in chronically ill and calorically deprived patients. In contrast to the expected selective decrease in circulating T3 levels in calorically restricted humans due to diminished T4 to T3 conversion, 5 d of starvation of two groups of male Sprague-Dawley rats resulted, paradoxically, in a greater decrease in serum T4 than in serum T3 levels. Kinetic studies show that starvation is associated with no change in the metabolic clearance rate (MCR) of T3, a 20% increase in the MCR of T4, a 67% reduction in turnover rate of T4, but only a 58% reduction in the turnover rate of T3. Moreover, in the first group of rats studied, direct chromatographic analysis of the isotopic composition of total body homogenates after the injection of 125I-T4 showed that 21.8% of T4 is converted to T3 in control rats and 28.8% in starved rats, suggesting that virtually all extrathyroidal T3 in starved and control rats is derived from the peripheral conversion of T4, and that there is little or no direct thyroidal secretion of T3. Our findings strongly point to a reduced thyroidal secretion of T4 as the primary cause of the observed reduction in circulating T3. Since the mechanisms leading to reduced levels of plasma T3 differ in humans and rats, it may be important to reexamine the use of liver homogenate preparations as models for study of the pathogenesis of the "low T3 syndrome" in humans.