Levels In Control Rats Research Articles

Chronic lability of the arterial blood pressure produced by electrolytic lesions of the nucleus tractus solitarii in the rat.

The purpose of this study was to assess the chronic effects of lesions of the nucleus tractus solitarii on the cardiovascular activity of rats. Arterial pressure and heart rate were recorded in conscious, unrestrained rats 7-216 days following placement of electrolytic lesions in the nucleus tractus solitarii. To assess the impact of environmental stimuli on the mean level and lability of the mean arterial pressure, cardiovascular activity was recorded under conditions of controlled and uncontrolled environmental stimulation. Nucleus tractus solitarii lesions abolished the reflex bradycardia to a phenylephrine-induced elevation in arterial pressure. A marked increase in the lability of the mean arterial pressure was produced with nucleus tractus solitarii lesions. The standard deviation of the mean arterial pressure, an index of lability, was 380% greater in rats with lesions than in control rats. The average mean arterial pressure, heart rate and heart rate variability were not significantly different between the lesion and control groups, regardless of the environmental conditions under which the measurements were made. Nucleus tractus solitarii lesions also greatly exaggerated the arterial pressure response to naturally occurring behaviors, such as eating and drinking. Vagal and beta-adrenergic blockade with methyl atropine and propranolol did not alter the average level or lability of the mean arterial pressure, although heart rate responses were similar in both groups. alpha-Receptor blockade with prazosin significantly lowered the mean arterial pressure in both lesion and control rats, but the decrease in mean arterial pressure was significantly greater in rats with nucleus tractus solitarii lesions (42 +/- 6 mm Hg, 38.5%) than in control rats (27 +/- 4 mm Hg, 23.2%). Prazosin also reduced the lability of the mean arterial pressure to control levels in rats with lesions. Thus, the chronic effects of nucleus tractus solitarii lesions in rats are to abolish the cardiomotor component of the baroreflexes and to produce extreme lability of the arterial pressure without altering the average level of the mean arterial pressure. Exaggerated blood pressure responses are seen in association with various behaviors. These effects are mediated primarily by changes in sympathetic discharge to the vasculature and are independent of the ambient level of environmental stimuli.

Urinary metallothionein and tissue metal levels of rats injected with cadium, mercury, lead, copper or zinc

Since Cd exposure results in a dose dependent increase in metallothionein level i urine, the present investigation was conducted to examine whether exposure to other divalent cations would also cause an elevation in urinary metallothionein. Female Sprague-Dawley rats were injected subcutaneously with either saline 5 μmol/kg/day of CdCl 2, HgCl 2, Pb(C 2H 3O 2) 2, CuSO 4 or ZnCl 2 for 5 days. Significant increase in hepatic Cu levels in rats treated with not only Cu, but also Zn, Cd or Hd, and in hepatic Zn levels in rats treated with Zn or Cd were noted. Similarly, renal Cu and Zn levels were elevated significantly in all groups except the Pb-injected group. These increases in tissue metal levels were presumably due to induction of metallothionein. The urinary metallothionein level in control rats on day 0, determined by radioimmunoassay, was 0.85 ± 0.17 mg/g creatinine. There was no significant change in urinary metallothionein level in rats given up to 5 injections of saline of Pb. Hg-injected rats showed 25-fold increase in urinary metallothionein after 5 injections, whereas C-injected rats had 9-fold increase. There were also 2- and 3-fold increases of urinary metallothionein by cu and Zn treatments for 5 days, respectively. Thus, urinary metallothionein levels were elevated in response to Cd, Hg, Cu, and Zn but not Pb; Hg had most profound effect at equimolar doses.

The acute effect of oestrogens on testosterone production appears not to be mediated by testicular oestrogen receptors

Scatchard binding analysis was performed to measure the cytoplasmic oestrogen receptor in the testis of rats. After treatment of rats with the antioestrogen tamoxifen no oestrogen receptor binding was found in testicular low speed supernatant between 12 and 96 h after treatment. Such tamoxifen-treated rats were used to study the acute effect of oestrogens on testosterone secretion, both in vivo and in vitro. Injection of oestradiol benzoate (50 μg, 24 h prior to experiment) resulted in a significant depression of basal and LH-stimulated plasma testosterone levels in control rats and this effect was unchanged in tamoxifen-pretreated rats. In vitro, oestradiol-17β also inhibited the LH-induced rise in testosterone secretion by isolated testicular interstitial cells. This inhibition was not affected if the rats had been pretreated with tamoxifen. These results indicate that the inhibitory effects of exogenous oestrogens on testicular testosterone production are probably not mediated by the oestrogen receptor.

Stress-induced testicular hyposensitivity to gonadotropin in rats. Role of the pituitary gland.

The time course of stress-induced testicular hyposensitivity to gonadotropins was studied in hypophysectomized or naloxone-treated rats exposed to various periods of immobilization. Blood was collected from a chronically indwelling intra-atrial catheter every hour for luteinizing hormone (LH) and testosterone (T) measurement. Eight hours of immobilization completely suppressed T secretion without significant effect on LH. Human chorionic gonadotropin (hCG, 5 IU/rat, i.m.) induced a marked increase in plasma T levels in normal control groups 3 h post-injection while in immobilized rats the response was completely abolished, even after only 30 min of stress. In hypophysectomized rats, as expected, plasma T levels were undetectable, but, contrary to results obtained in normal animals, hCG induced a similar increase of plasma T levels both in control and stressed rats. Immobilization stress failed to inhibit plasma T values in hypophysectomized rats pretreated for 4 days with human menopausal gonadotropin (hMG) + hCG, while it did so in similarly treated normal animals. Naloxone induced a rise of plasma LH and T levels in control rats, but did not antagonize the stress-induced fall of plasma T concentration. In all groups, steroid testicular content mimicked variations of plasma T values. In particular, in stressed animals the lack of accumulation of testicular 17-hydroxyprogesterone probably reflected a normal activity of 17-20 lyase. These results indicate that stress induces very rapidly a state of Leydig cell hyposensitivity to gonadotropins and a blockade of T biosynthesis. The causal relationship between the two effects is presently not clear but these events seem to be due to stress-induced release of an inhibitory factor of pituitary origin other that endorphin.

Systemic and regional hemodynamic effects of endogenous vasopressin stimulation in rats.

We investigated the systemic and regional hemodynamic alterations induced in normotensive anephric rats by stimulation of endogenous vasopressin with an acute sodium and fluid load and following vasopressin inhibition with a specific antagonist of its vasoconstricting action. Blood pressure and total peripheral resistance were significantly higher and cardiac output was lower in rats with stimulated vasopressin, and all were reversed to near control levels in rats receiving the vasopressin inhibitor. Regional blood flows were diminished in most organs and local vascular resistance was elevated compared with control animals, but the magnitude of change varied widely. In fact, heart blood flow did not decrease significantly and brain blood flow actually increased indicating small or no change in vascular resistance of these organs. Moreover, fractional distribution of the diminished cardiac output to these organs was significantly higher, so that blood flow to vital organs was maintained at the expense of blood flow to other tissues. In rats that received the vasopressin antagonist after the saline infusion, regional blood flows were similar to those of control animals. Blood pressures at the base line and after hypertonic NaCl infusion correlated closely with the corresponding plasma levels of control and stimulated vasopressin.

Negative feedback of secretion of follicle-stimulating hormone by the pituitary gland of developing male rats.

Rabbit antiserum to human seminal plasma inhibin (hSPI) was administered subcutaneously to developing male rats of 5, 10, 14, 17 and 24 days of age and the size of the endogenous FSH rise in serum was measured. The FSH levels were threefold higher on day 9 and 1.5-fold higher on days 14 and 18 when compared with levels in control rats treated with normal rabbit serum. Furthermore, the in-vitro binding capacity of pituitary plasma membrane to 125I-labelled hSPI declined with increase in age of the rats. Thus, the results of the present study suggest that the sensitivity of the testicular inhibin-FSH feedback relationship is related to age-dependent changes in pituitary binding of inhibin.

Administration of antisomatostatin serum to rats reverses the inhibition of pulsatile growth hormone secretion produced by injection of metergoline but not yohimbine.

We attempted to determine whether release of endogenous somatostatin (SS) in rats might mediate the apparent inhibition of growth hormone (GH) secretion produced by metergoline of yohimbine injection. Plasma GH levels in adult male rats bearing chronic right-atrial cannulae were measured at 15-min intervals during a 4-hour period around the onset of the daily dark period. Plasma GH levels in control rats (vehicle-injected) rose rapidly from low levels (< 10 ng/ml) just before darkness to very high levels (> 300 ng/ml) around the onset of the dark period, then declined to low values within 2 h. Injection of the serotonin receptor antagonist metergoline (5 mg/kg) or the adrenergic blocker yohimbine (10 mg/kg) 2.25 h before darkness significantly suppressed the subsequent rise in plasma GH levels. The effect of metergoline, but not yohimbine, on plasma GH was markedly reversed when animals were injected intravenously with anti-SS serum (0.5 ml) 1 h after drug administration. These data suggest that circulating SS may mediate the GH inhibition produced by injection of a serotonin receptor blocker; however, other factors are apparently involved in the suppression of GH secretion by yohimbine.

Influence of diet palatability on maintenance feeding behavior in rats with dorsolateral tegmental damage

Lesions in the dorsolateral tegmentum that depleted hypothalamic norepinephrine induced (a) substantial hyperphagia and weight gains in rats maintained on either high-fat or wet-mash diets, (b) moderate overeating and body weight gains in rats maintained successively on 0.4, 0.3, 0.2, and 0.1% quinine high-fat diets, and (c) body weight maintenance at same-diet control levels in rats maintained successively on 0.2, 0.4, and 0.6% quinine wet-mash diets. Similarities and differences of the present findings with reference to previous observations obtained from rats with ventromedial hypothalamic lesions are discussed.

Effects of noradrenaline and nicotinic acid on plasma free fatty acids and oxygen consumption in cold-adapted rats.

A 3-h noradrenaline (NA) infusion (1.5 microgram kg-1 min-1) produced a sustained enhanced oxygen consumption (O2 cons.) in cold-adapted rats. Plasma free fatty acid (FFA) levels were elevated by NA in control and in cold-adapted rats, but to lesser extent in cold-adapted rats; the increase was maintained at a plateau in both groups during the entire period of NA infusion. A 1-h nicotinic acid (Nic A) infusion (1.5 mg kg-1 min-1) added to the NA infusion inhibited the calorigenic response to NA in cold-adapted rats and reduced the elevated plasma FFA concentration in control and in cold-adapted rats to values below basal levels. However, when the Nic A infusion was stopped, the O2 cons. was increased again in cold-adapted rats by the uninterrupted NA infusion, without the simultaneous increase of the plasma FFA concentration; the plasma FFA concentration was maintained in cold-adapted rats below basal values and merely brought back to basal levels in control rats. From these results, it is suggested that plasma FFA are not an essential substrate to the calorigenic response to NA observed in cold-adapted rats, as 85% of the response can occur when the plasma FFA concentration is very low.

Alterations in the Processing of Rat-Liver Ribosomal RNA Caused by Cycloheximide Inhibition of Protein Synthesis

Cycloheximide given in vivo at low doses (2--5 mg/kg body weight) causes within 30 min a complete inhibition of protein synthesis in rat liver. The labelling of nuclear proteint is also strongly inhibited. Under these conditions, the amount of nucleolar 45-S pre-rRNA and its [14C]-orotate labelling remain unaffected for at least 4 h. These results show that initially the rates of synthesis and processing of 45-S pre-rRNA are not appreciably altered. On the other hand, drastic alterations in the 45-S pre-rRNA processing pathways occur at the early stages of cycloheximide action. Formation of 18-S rRNA is abolished and that of 28S rRNA is reduced to about half the level in control rats. This dichotomy in the production of the two ribosomal particles may be correlated with a block in the formation of 41-S and 21-S pre-rRNA. Generation of 36-S and 32-S pre-rRNA is still taking place, but the rate of their processing to nucleolar 28-S rRNA is decreased, thus causing the accumulation of these two pre-rRNA species. In parallel, processing of 45-S pre-rRNA to an aberrant 39-S rRNA species is markedly enhanced. The results obtained show that the channelling of nucleolar pre-rRNA along alternative processing pathways is under stringent control by the continuous supply of critical protein(s).

Reduction of blood and liver cholesterol in the rat by straight and branched chain alkyl amines.

AbstractThe activities of a branched chain and several straight chain amines (C12 to C18 chain length), and the azasteroid 25‐aza‐5α‐cholestane were compared with those of 20,25‐diazacholesterol dihydrochloride, which is a potent hypocholesterolemic agent in the rat. These amines and azasteroids inhibit the Δ24‐sterol reductase system in the tobacco hornworm,Manduca sexta (L.), and also block the conversion of C28 and C29 plant sterols to cholesterol, with a resulting accumulation of desmosterol. The effects of these compounds in the rat were determined on body weight gain, cholesterol, desmosterol, and lipid composition of blood, feces, liver, and epididymal fat pad weight. The two azasteroids and the branched chain amine, N,N‐dimethyl‐3, 7,11‐trimethyldodecanamine, had the greatest effect, reducing total plasma lipids and plasma sterols to approximately 40–50% of the levels in control rats and produced a concomitant increase in plasma and liver desmosterol. The branched chain dodecanamine caused a reduction in both feed consumption and body weight gain. The branched and straight chain dodecanamines also severely reduced epididymal fat pad weight. Our results demonstrate that the simple azasteroid, 25‐aza‐5α‐cholestane, is a more potent inhibitor of cholesterol biosynthesis than the diazasterol and that the Δ24‐sterol reductase system in a mammal can be inhibited by simple, nonsteroidal, acyclic amines.

Inhibition of chemical carcinogenesis: Increased activity of soluble RNA polymerase in the liver of rats protected against 3′MeDAB hepatocarcinogenesis by dietary chloramphenicol

Soluble RNA polymerases (nucleotidyl transferases, EC 2.7.7.6) were isolated from liver nuclei of rats that had been pair-fed diets containing the hepatocarcinogen 3′methyl- 4-dimethylaminoazobenzene ( 3′MeDAB, 0·06%) either alone or in combination with chloramphenicol (CAP, 2%), an inhibitor of azo dye carcinogenesis. DEAE Sephadex A- 25 chromatography of crude nuclear extracts (fraction IV protein) revealed 2 major peaks of enzyme activity which were equated with RNA polymerases I and II on the basis of order of elution and sensitivity to α-amanitin. The specific activities of both enzymes, in particular RNA polymerase I, were significantly increased after 4 days on diets containing CAP or both 3′MeDAB and CAP. Rats protected from 3′MeDAB carcinogenesis by CAP showed the greatest increase, which exceeded that in the group fed dye alone by 292% for polymerase I and 116% for polymerase II. Increases in both RNA polymerase activities were probably not a consequence of altered affinity for the substrate UTP. RNA polymerase activity was not altered by feeding the 3′MeDAB diet for 4 days, but after 10 days there was a 340% increase in the specific activity of enzyme I and a 14% increase in the specific activity of enzyme II relative to levels in control rats. The total nuclear protein content was significantly increased in rats fed 3′MeDAB or both 3′MeDAB and CAP for 4 days. Crude polymerase extracts contained 4–6% of the total nuclear protein and 83–87% of the RNA polymerase activity present in isolated nuclei. There was a significant increase in the amount of nuclear sap protein extracted after feeding 3′MeDAB for 4 days. Differences in nuclear RNA synthesis between experimental groups were insensitive to presacrifice starvation and altered feeding and lighting schedules; neither were they due to differential losses of RNA polymerases during the nuclear isolation procedure or to preferential extraction of these enzymes from isolated nuclei in the various groups. We conclude that the differences in liver nuclear RNA synthesis between 3′MeDAB-fed rats and rats protected against 3′MeDAB-induced hepatocarcinogenesis by concurrent CAP administration are at least partly due to differences in the activity and/or amount of soluble RNA polymerases.

Sequential Quantitation of Circulating Immune Complexes in Syngeneic and Allogeneic Rats Bearing Moloney Sarcomas

A Raji cell radioimmunoassay was employed to quantitate serially circulating immune complexes (CIC) in the sera of syngeneic BN rats and allogeneic Lewis rats bearing BN Moloney sarcomas. In syngeneic BN hosts the levels of CIC attained and the time-course of detection were related to the tumor dose, tumor mass, and regressive or progressive course of the tumor. In general, syngeneic rats that received larger tumor doses developed larger tumors and greater maximum levels of CIC. However, the amount of CIC was not always directly proportional to the tumor size, although this was nearly the case with regressor BN and Lewis rats. In rats with regressing tumors, CIC decreased to insignificant levels as the tumors disappeared. Progressor BN rats that received 20 and 10 X 10(6) tumor cells had higher and more sustained levels of CIC, but, shortly before the hosts died, despite an increase of tumor size, there was a decline of CIC. Progressor BN rats that received an initial inoculum of 0.5 X 10(6) tumor cells that grew to 44 mm maximum mean diameter had levels of CIC which were only slightly above levels of control rats. All allogeneic Lewis hosts rejected BN Moloney sarcomas, but had transient low levels of CIC coincident with tumor growth. Lewis rats had lower levels of CIC than BN rats bearing comparable masses of sarcoma.

Influence of spironolactone pretreatment on pharmacokinetics and metabolism of digitoxin in rats.

The influence of pretreatment with spironolactone (84 mg/kg at 3 days, twice per day) on the tritium levels in plasma, urine and feces of female SD-rats (n=9) was investigated at various time periods after oral administration of 25mug/kg -3H-digitoxin. In plasma, the concentrations of total radioactivity are reduced in pretreated animals to about 20% of tritium levels in control rats, while the half-life of radioactivity in both groups is almost identical, 2.9 days in pretreated rats and 2.8 days in controls. The lower plasma levels of tritium in pretreated rats coincide with a six-fold decrease in the urinary -3H-elimination and a corresponding increase in the fecal excretion. This is due to a higher biliary clearance of tritiated products in the early phase of elimination. The separation of the excretion products by TLC shows that spironolactone pretreatment enhances the splitting of the glycosidic bonds of digitoxin. The amount of digitoxigenin-bis-digitoxoside and of digitoxigenin-mono-digitoxoside excreted in urine and feces within 96 hrs is four and ten times greater than that recovered in control animals, respectively. The formation of the hydroxylation products digoxin and digoxigenin-bis-digitoxoside is decreased from 50% of the total excreted radioactivity in control to 15% in pretreated rats. The conjugation reactions with glucuronic and sulfuric acid are increased after pretreatment with spironolactone. Thus, the effect of spironolactone on digitoxin kinetics is apparently related to an enhancement of the hepatic excretory mechanism as well as to an enhanced metabolism.

Intestinal absorption of amino acids in rats infected with Nematospiroides dubius

1. In rats infected with Nematospiroides dubius small intestinal methionine transport was significantly reduced from uninfected controls within 1 day of infection, reaching a minimum 4–13 days after infection, after which time recovery of normal absorptive function gradually occurred. 2. Proline and ornithine transport was significantly reduced from control levels in rats infected for 7 days 3. Addition of glucose to the serosal fluid failed to influence the rate of methionine transport in controls or in rats infected for 7 days.

Hypophyseal-adrenocortical role in urinary excretion of epinephrine and norepinephrine in hypophysectomized and adrenalectomized rats.

Experiments were designed to study the 24 hr urinary excretion of epinephrine and norepinephrine in hypophysectomized and adrenalectomized rats. One month after hypophysectomy there was a marked decline in urinary excretion of epinephrine. Norepinephrine excretion was greatly increased 15 days after hypophysectomy and one month after adrenalectomy. The hypophysectomized rats were also administered with 4 IU of ACTH daily for 23 days. After the 3rd injection of ACTH, epinephrine urinary excretion demonstrated a gradual increase. After the 14th injection, urinary epinephrine was not different statistically from control rats. ACTH treatment augmented urinary norepinephrine after the first injection but subsequent changes were insignificant. The volume of urine excreted declined markedly 1 month after hypophysectomy but this decline was not correlated with catecholamine excretion. ACTH administration also modified urinary volume in hypophysectomized rats to the level of control rats. The results suggest that ...

Pituitary secretion of prolactin, luteinizing hormone and follicle-stimulating hormone in adult female rats treated neonatally with oestrogen.

SUMMARY The serum and pituitary levels of prolactin, luteinizing hormone (LH) and follicle-stimulating hormone (FSH) were determined by radioimmunoassay in adult female rats treated neonatally with oestrogen and were compared with levels in normal cyclic rats at 90, 150 and/or 180 days of age. The serum level of prolactin was significantly higher and its pituitary content and concentration were lower in oestrogenized rats than in control rats at early prooestrus and on the 2nd day of dioestrus. The level of LH in the serum of oestrogenized rats was similar to the level in control rats at pro-oestrus and was higher than that of the controls at dioestrus. Pituitary levels of LH were lower in oestrogenized rats than in control rats at both pro-oestrus and dioestrus. The serum and pituitary levels of FSH in the oestrogenized rats were intermediate between the values found at dioestrus and at pro-oestrus in the controls. The results demonstrate that the pituitary of the neonatally oestrogenized female rat constantly secretes considerable amounts of these hormones.

Circulation to the brain of the rat during acute and prolonged respiratory changes in the acid-base balance

The fraction of the cardiac output distributed to the brain was studied with a particle distribution method at different acutely induced arterialPCO2 levels in control rats and in rats kept during 24 h before the experiment in an atmosphere containing either 10% CO2 in air (prolonged hypercapnia) or 10% O2 in N2 (hypoxic hyperventilation producing prolonged hypocapnia). The curve relating the fraction of the cardiac output distributed to the brain and thePa CO2 is shifted upwards and to the left after prolonged hypocapnia, and downwards and to the right after prolonged hypercapnia. A similar shift is observed when orthosympathetic vasoconstrictor activity is eliminated in the three groups of rats by alpha-adrenergic receptor blockade. The changes in the fraction of the cardiac output perfusing the brain are essentially due to modifications in the cerebral blood flow, since the cardiac output was not significantly influenced by the alterations in thePa CO2. The results are discussed in relation to the changes occurring in the CO2/HCO3− dissociation curve in blood and brain during prolonged respiratory changes in the acid-base balance.

Myocardial and splenic levels of catecholamines in burn shock.

SummaryThe norepinephrine and epinephrine content of ventricular cardiac muscle and spleen were analyzed in 2 groups of anesthetized white rats. One group served as controls, while the other group was subjected to burn shock induced by immersing the lower 1/2 of the body for 90 sec in water heated to 90°C. Myocardial norepinephrine and epinephrine levels of control rats averaged 0.74 ± 0.15 and 0.07 ± 0.06 μg/gm, respectively. In burn shock, norepinephrine decreased markedly to 0.26 ± 0.20 μg/gm (p <.003), while epinephrine rose to 0.24 ± 0.07 μg/gm (p<.003). On the other hand, splenic norepinephrine rose from 0.55 ± 0.15 to 1.02 ± 0.25 μg/gm (p<.05), while epinephrine content declined from 0.36 ± 0.12 to 0.09 ± 0.06 μg/gm (p<.003) in burn shock. Excessive sympathetic nervous system stimulation, or the formation of toxic substances may be involved in reducing norepinephrine stores of the myocardium in burn shock. Unlike the depletion of splenic norepinephrine in hemorrhagic shock, the norepinephrine conte...