Effect of renal denervation on phosphate excretion in endotoxemic rats

Our previous studies showed that endotoxin (Et) administration causes hypophosphaturia in the presence of PTH. In this study, we tested the hypothesis that enhanced renal nerve activity during endotoxemia is responsible for hypophosphaturia. Two weeks after bilateral renal denervation, phosphate excretion was examined in endotoxemic Wistar rats (300 g body weight). Renal clearance studies were performed before and after 4 mg/kg body weight Escherichia coli Et administration. Et administration resulted in a marked fall in glomerular filtration rates of innervated rats (n=12, from 2.09 +/- 0.11 ml/min to 0.89 +/- 0.15 ml/min, P<0.005) compared to saline-treated innervated rats (n=7, from 1.98 +/- 0.19 ml/min to 1.76 +/- 0.16 ml/min). The glomerular filtration rate of renal denervated rats was the same for saline-treated rats (n=9, from 2.67 +/- 0.92 ml/min to 1.69 +/- 0.12 ml/min) and Et-treated rats (n=10, from 2.37 +/- 0.19 ml/min to 1.52 +/- 0.07 ml/min). Fractional phosphate excretion was significantly reduced after Et challenge in innervated rats (from 24.0 +/- 3.3% to 11.8 +/- 2.2%, P<0.0001) compared to saline injection in innervated rats (from 26.9 +/- 3.9% to 33.0 +/- 1.6%). Although renal denervation improved the hypophosphaturia in comparison to the innervated rats, fractional phosphate excretion was still lower in Et-treated rats (from 28.8 +/- 5.0% to 18.0 +/- 4.7%, P<0.005) than in saline-treated rats (from 30.2 +/- 6.1% to 38.7 +/- 4.2%). In conclusion, our data did not support the hypothesis that renal nerves have an important role in reducing renal phosphate excretion during acute endotoxemia.     

Intermediate filament cytoskeletal proteins associated with bovine lens native membrane fractions

1. Arginine can be produced in the kidney from citrulline. An important source of circulating citrulline is the intestinal breakdown of glutamine. Consequently, partial enterectomy leads to decreased plasma citrulline levels. The aim of the present study was to investigate the effect of diminished arterial citrulline levels on renal arginine production and total-body free arginine pools.2. Renal amino acid metabolism was studied 24 h after 75% small bowel resection in rats fasted overnight (16 h) (n=12; total fast 40 h). Sham-operated (n=9) and non-operated 16-h and 40-h fasted controls were studied in parallel (n=8/n=7). During anaesthesia, L-(2, 3-3H)-arginine and para-aminohippuric acid were infused until steady state. Subsequently, arterial and renal venous blood samples were taken. Concentrations of para-aminohippurate and amino acids and specific activity of arginine and citrulline were measured to calculate renal plasma flow, net renal uptake or release, and unidirectional influx or efflux of arginine and citrulline, as well as whole-body arginine turnover.3. Arterial citrulline was decreased in enterectomized rats compared with sham-operated rats (23+/-3 versus 44+/-6 microM). Net renal citrulline uptake and arginine release were almost stoichiometric (-36+/-7 and 38+/-6 nmol.min-1. 100 g-1 body weight respectively in sham-operated rats) and were both diminished by 50% in enterectomized versus sham-operated rats. In all groups, net renal arginine production accounted for less than 10% of whole-body rate of arginine appearance (488 nmol.min-1.100 g-1 body weight in the sham group). Despite decreased net renal citrulline consumption and renal arginine production in enterectomized rats, whole-body rate of arginine appearance and arterial arginine did not change significantly.4. In conclusion, net renal arginine production is reduced 24 h after 75% enterectomy in fasted rats. However, this does not have important effects on whole-body arginine production.     

Neural factors contributing to renin release during reduction in renal perfusion pressure and blood flow in cats

1. The participation of neural mechanisms in mediating the renin release induced by reduction of renal perfusion pressure was explored in anaesthetized cats by comparing renin release from the two kidneys, one acutely denervated and the other intact. 2. Suprarenal aortic stenosis of 10 min duration reduced renal perfusion pressure to 50 mmHg and halved blood flow to both kidneys, but cause a greater release of renin from the innervated kidney than from the contralateral denervated one (increments of 72 +/- 17 and 29 +/-20 pmol/min respectively). 3. A study of the time-course of the response during aortic stenosis of 30 min duration showed early release of renin from the innervated kidney at a time (5 min) when little release occurred from the denervated one. In later samplings (15 and 30 min) the response of the innervated kidney levelled out at somewhat lower values, and that of the denervated organ progressively increased, but remained smaller than on the side with intact nerves. 4. There was no parallelism between renin release and renal vasomotor changes induced by aortic stenosis, as vasomotor changes were equal in the two kidneys and remained constant from beginning to end of stenosis. It is concluded that a significant part of the renin release induced by aortic stenosis is dependent on neural mechanisms: the neural differs from the non-neural component in being of more rapid onset and probably of shorter duration.     

Respiratory and cardiovascular interactions in ducks: the effect of lung denervation on the initation of and recovery from some cardiovascular responses to submergence

Lung denervation in ducks, by sectioning all vagal branches to one lung following mid-cervical vagotomy on the other side, resulted in immediate bradycardia and fall in breathing frequency. Some 3-5 weeks after lung denervation breathing frequency was within the normal range but the lung inflation reflex, present in unilaterally vagotomized sham-operated ducks, was abolished. During 2 min dives there were no significant differences between sham-operated and denervated ducks in heart rate, arterial blood pressure, blood gas tensions and pH(a). However, during recovery from diving heart rate increased more slowly in denervates and breathing rate was significantly below that attained by shams, although tidal volume rose to a maximum increase of 139% to a maximum of 225% of the pre-dive value in denervates in contrast to a maximum increase of 139% of pre-dive in sham-operated ducks. Both sham-operated and denervated ducks exhibited a significant fall in diastolic blood pressure 60 sec after emergence...     

Molecular cloning and characterization of CDEP, a novel human protein containing the ezrin-like domain of the band 4.1 superfamily and the Dbl homology domain of Rho guanine nucleotide exchange factors

BACKGROUND/AIMS: Liver cirrhosis and portal hypertension are associated with hyperdynamic circulation. Portacaval shunts are widely used to prevent recurrent hemorrhage, but the hemodynamic effects caused by these procedures have not been well characterized in cirrhosis. We therefore compared the hemodynamic effects of both end-to-side and side-to-side portacaval shunts in normal and cirrhotic rats. METHODS: Sprague-Dawley rats were divided into six groups according to the operations they underwent. End-to-side or side-to-side portacaval shunts were performed in both rats with cirrhosis induced by bile duct ligation and sham-operated rats. Systemic and regional blood flows were measured by the radioactive microsphere method. RESULTS: Portal pressures in the shunted rats decreased significantly. Cardiac index in cirrhotic rats (557 +/- 27 ml.min-1.kg-1) was significantly higher than controls (455 +/- 21 ml.min-1.kg-1), but the two types of shunts did not further increase cardiac index in either the cirrhotic or the sham-operated rats. After shunting, hepatic arterial flows approximately doubled. Portal tributary blood flows in the end-to-side shunted sham (108 +/- 13 ml.min-1.kg-1) and cirrhotic (139 +/- 19 ml.min-1.kg-1 groups were significantly higher than their respective controls (62 +/- 8 and 76 +/- 5 ml.min-1.kg-1). Portosystemic shunting indices were > 99% in both the end-to-side and side-to-side shunted groups in cirrhotic and sham-operated rats. CONCLUSIONS: The hyperdynamic circulation in cirrhotic rats was not augmented by portacaval shunting operations (either end-to-side or side-to-side), despite essentially total portosystemic blood diversion. Compensatory increase in the hepatic arterial blood flow to the liver remained intact even in cirrhotic rats. A selective redistribution of cardiac output to the mesenteric vascular bed was observed after the shunting procedure. However, there were no significant differences in hemodynamics between the end-to-side and side-to-side shunted groups.     

The effect of the hepatic nerves on the disposition of a mixed meal by conscious dogs

We examined the disposition of a mixed meal by nine conscious dogs fasted for 24 hours with surgical hepatic denervation. The results were compared with those from identical studies carried out previously in 13 hepatic-innervated dogs. Net gut release of glucose and gluconeogenic precursors (assessed with the arteriovenous difference technique), the resulting blood glucose and plasma insulin concentrations, and the hepatic glucose load were remarkably similar in the two groups. Net hepatic glucose uptake was 4.8 +/- 3.6 g in hepatic-denervated and 7.7 +/- 3.3 g in hepatic-innervated dogs. Cumulative net hepatic lactate release in hepatic-denervated dogs was 4.3 +/- 1.4 g of glucose equivalents, half the value for hepatic-innervated dogs. Net hepatic carbon intake was similar in the two groups. Hepatic lipogenesis, oxidation, and net glycogen synthesis were qualitatively similar between groups. In conclusion, the disposition of a mixed meal by hepatic-innervated and hepatic-denervated dogs was very similar. Subtle alterations in net hepatic balance of substrates (tendencies toward decreases in net hepatic glucose uptake and lactate release) made net carbon retention in denervated livers virtually identical with that in innervated livers. When other compensatory mechanisms are intact, hepatic denervation does not significantly alter hepatic disposition of a mixed meal.     

The utility of K-correction to adjust for a defensive response set on the MMPI

We studied whether denervation affects the expression of tau, in particular phosphorylated tau, and how it is degraded in rat soleus muscles. Immunoblot analysis showed a high molecular weight, approximately 110 kDa (big tau), in normal muscle. Tau levels increased significantly in denervated muscles treated with chloroquine (a lysosomotrophic agent) and in untreated ones, as compared to levels of similarly treated contralateral, innervated muscles. Most of the tau in the innervated and denervated muscles was phosphorylated. Immunohistochemically, tau and beta-tubulin colocated in the sarcoplasm of innervated, saline-treated (intact) muscle, but the staining intensities were very weak. Both proteins, however, were expressed extensively in these areas in the denervated muscles from saline-treated rats. In the denervated muscle of chloroquine-treated rats there were numerous autophagic vacuoles in the sarcoplasm, and phosphorylated-tau accumulation was marked within these vacuoles, indicative that tau first was taken into autophagic, vacuoles by nonselective autophagy then degraded via the lysosomal as well as the nonlysosomal calpain system. Our findings suggest that phosphorylated big tau accumulates with beta-tubulin in denervated muscular atrophy, possibly in order to maintain or preserve the integrity of the muscle fiber during progressive atrophy or regeneration.     

The role of acetylcholine receptors and acetylcholinesterase activity in the development of denervation supersensitivity

Strips of muscle from innervated and denervated rat hemidiaphragm were tested for sensitivity to acetylcholine and to carbachol. For both agonists, denervation (6-8 days) produced notable supersensitivity. However, the increase in sensitivity to acetylcholine (ca. 600-fold) was much greater than that to carbachol (ca. 51-fold). Denervation also produced an increase in [3H]alpha-bungarotoxin binding (ca. 20-fold), presumably indicative of an increase in the number of acetylcholine receptors. In addition to causing increases in tissue sensitivity and receptor number, denervation caused a marked loss of acetylcholinesterase activity (ca. 70%) and a modest loss of butyrylcholinesterase activity (ca. 20%). When innervated muscle was pretreated with eserine (5 X 10(-5) M), there was a loss of acetylcholinesterase activity (ca. 86%) and butyrylcholinesterase activity (ca. 36%). Simultaneously, there was an increase in tissue sensitivity to acetylcholine (ca. 26-fold). When denervated muscle was pretreated with eserine, there was no loss of enzyme activity beyond that caused by denervation. Furthermore, eserine pretreatment did not increase denervated muscle sensitivity to acetylcholine. The data suggest that both an increase in acetylcholine receptors and a decrease in acetylcholinesterase activity contribute to the phenomenon of denervation supersensitivity.     

Interactions between nitric oxide and renal nerves on pressure-diuresis and natriuresis

The present study examined the effect of renal denervation on the impairment of the pressure-diuresis response produced by nitric oxide synthesis blockade. The experiments were performed in Inactin-anesthetized Munich-Wistar rats. The animals with innervated kidneys had lower baseline values of renal blood flow, GFR, sodium excretion (UNaV), and urine flow (V) than rats with denervated kidneys. Also, renal denervation shifted pressure-diuresis and natriuresis toward lower pressures. A low dose of N(omega)-nitro-L-arginine methyl esther (NAME, 3.7 nmol/kg per min) reduced UNaV and the fractional excretion of sodium (FENa) and blunted pressure-natriuresis only in rats with innervated kidneys, whereas it had no effects in rats with denervated kidneys. A medium dose of NAME (37 nmol/kg per min) lowered FENa only in rats with innervated kidneys. The administration of NAME (37 nmol/kg per min) blunted pressure-diuresis and natriuresis in kidneys with or without the renal nerves, but the effect was more pronounced in rats with innervated kidneys. A high dose of NAME (3.7 micromol + 185 nmol/kg per min) increased UNaV and FENa only in rats with innervated kidneys, whereas it reduced GFR, V, UnaV, and FENa in rats with denervated kidneys. However, pressure-natriuresis and diuresis were blunted by this high dose of NAME independently of the presence or absence of renal nerves. These results demonstrate that renal nerves potentiate the renal effects of low doses of NAME on renal function and pressure-diuresis and natriuresis. However, high doses of NAME abolish pressure-diuresis independently of renal nerves, and the natriuretic effect of NAME in innervated kidneys may be attributed to reflex inhibition of sympathetic tone due to the rise in arterial pressure.     

Influence of the renal sympathetic nerves on renal renin and angiotensinogen gene expression in spontaneously hypertensive rats during development

OBJECTIVE: To investigate the influence of renal sympathetic denervation on renin and angiotensinogen gene expression in the kidney during growth and the development of hypertension in spontaneously hypertensive rats (SHR). Comparative studies were undertaken in age-matched normotensive Wistar rats. DESIGN: Four-week-old SHR and Wistar rats were subjected to either denervation of the left kidney or sham operation. At age 5, 7 or 9 weeks the rats were lightly anaesthetized, carotid blood pressure was measured, a blood sample was taken and both kidneys were removed. METHOD: Plasma renin activity was measured by radioimmunoassay, and renal renin and angiotensinogen messenger RNA (mRNA) levels were measured by Northern blot hybridization followed by densitometric analysis. RESULTS: In 5- and 7-week-old SHR the renin mRNA level in the left kidney was significantly suppressed compared with that in the sham-operated right kidney and with the level in 9-week-old SHR. The renal renin mRNA level in sham-operated SHR decreased significantly with increasing age, whereas in the Wistar rats the renal renin mRNA level did not change at any age and was not affected by renal denervation. The renal angiotensinogen mRNA level gradually increased with age in both rat strains and was not affected by denervation, but much higher levels were attained in the Wistar rats than in the SHR. CONCLUSION: Renal angiotensinogen gene expression was depressed in the SHR, with little evidence of neural regulation at any age in the SHR or the Wistar rats. However, in the SHR the renal sympathetic nerves elevated renal renin gene expression in the prehypertensive stage, but their influence decreased as hypertension developed.     

Alterations in contractility and intracellular Ca2+ transients in isolated bundles of skeletal muscle fibers from rats with chronic heart failure

To determine if chronic heart failure (CHF) leads to functional or structural alterations of skeletal muscle, we compared intracellular Ca2+ signaling, contractility, and the rate of fatigue development, together with electron microscopy (EM), in skeletal muscle preparations from rats with myocardial infarction-induced CHF versus sham-operated control rats. Bundles of 100 to 200 cells were dissected from the extensor digitorum longus (EDL) muscle of control (n = 13) and CHF (n = 19) rats and were either loaded with aequorin or fixed for EM. Muscles from CHF rats exhibited depressed tension development compared with control muscles during twitches (1.4 +/- 0.2 versus 2.8 +/- 0.7 g/mm2, P < .05) and maximal tetani (5.3 +/- 1.4 versus 10.7 +/- 2.4 g/mm2, P < .05). Depressed tension in CHF was accompanied by reduced quantitative [Ca2+]i release during twitches (0.7 +/- 0.1 versus 0.4 +/- 0.1 microM, P < .05) and during maximal tetani (1.8 +/- 0.3 versus 0.9 +/- 0.2 microM, P < .05). Skeletal muscle from CHF rats also demonstrated prolonged intracellular Ca2+ transients during twitches and tetani and accelerated fatigue development. EM revealed a lack of cellular atrophy in the CHF rats. In conclusion, EDL skeletal muscle from rats with CHF had intrinsic abnormalities in excitation-contraction coupling unrelated to cellular atrophy. These findings indicate that CHF is a condition accompanied by EDL skeletal muscle dysfunction.     

Cholecystokinin elicits the complete behavioral sequence of satiety in rats.

Observed and scored the behavior of intact rats and rats with chronic gastric fistulas during a 60-min test period when they were offered liquid diet after 17 hr of food deprivation. The same 5 adult male Sprague-Dawley rats were employed in 2 experiments. Intact Ss and Ss with closed fistulas displayed a specific behavioral sequence at the end of each meal: They stopped eating, engaged in grooming and exploration for a short time, and then rested or slept. Thus, a fixed behavioral sequence characterized satiety in Ss. Although the behavioral sequence of satiety was fixed, the cessation of feeding was not a sufficient condition for the appearance of the rest of the sequence: Quinine adulteration of the liquid diet stopped sham feeding but did not elicit the complete sequence. Intraperitoneal injection of the intestinal hormone cholecystokinin during sham feeding, however, elicited the complete sequence of satiety. The observation that cholecystokinin not only stopped feeding but elicited the complete sequence of satiety supports the hypothesis that endogenous cholecystokinin is a satiety signal for the rat. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Decreased [3H]ouabain binding sites in skeletal muscle of rats with chronic heart failure

Abnormalities intrinsic to skeletal muscle are thought to contribute to decrements in exercise capacity found in individuals with chronic heart failure (CHF). Na+-K+-adenosinetriphosphatase (the Na+ pump) is essential for maintaining muscle excitability and contractility. Therefore, we investigated the possibility that the number and affinity of Na+ pumps in locomotor muscles of rats with CHF are decreased. Myocardial infarction (MI) was induced in 8 rats, and a sham operation was performed in 12 rats. The degree of CHF was assessed approximately 180 days after surgery. Soleus and plantaris muscles were harvested, and Na+ pumps were quantified by using a [3H]ouabain binding assay. At the time of muscle harvest, MI and sham-operated rats were similar in age (458 +/- 54 vs. 447 +/- 34 days old, respectively). Compared with their sham-operated counterparts, MI rats had a significant amount of heart failure, right ventricular-to-body weight ratio was greater (48%), and the presence of pulmonary congestion was suggested by an elevated lung-to-body weight ratio (29%). Left ventricular end-diastolic pressure was significantly increased in the MI rats (11 +/- 1 mmHg) compared with the sham-operated controls (1 +/- 1 mmHg). In addition, mean arterial blood pressure was lower in the MI rats compared with their control counterparts. [3H]ouabain binding sites were reduced 18% in soleus muscle (136 +/- 12 vs. 175 +/- 13 pmol/g wet wt, MI vs. sham, respectively) and 22% in plantaris muscle (119 +/- 12 vs. 147 +/- 8 pmol/g wet wt, MI vs. sham, respectively). The affinity of these [3H]ouabain binding sites was similar for the two groups. The relationship between the reduction in Na+ pump number and the reduced exercise capacity in individuals with CHF remains to be determined.     

Induction of macrophage migration inhibitory factor messenger ribonucleic acid in rat forebrain by reperfusion

To evaluate the impact of uremia and associated caloric restriction on physiologically pulsatile growth hormone (GH) release, we used deconvolution analysis of spontaneous plasma GH profiles in 5/6-nephrectomized male rats (NX, N = 9). Three different normal renal function sham-operated groups were used: rats fed a normal diet ad libitum (SAL, N = 9); NX pair-fed rats (SPF, N = 6); NX rats pair-fed for protein ingestion but calorically supplemented up to the energy intake of SAL (SPF+, N = 8). Severe renal failure was confirmed by much higher (P < 0.001) BUN in NX than sham groups. NX rats were growth retarded as shown by reduced (P < 0.01) weight and length gains as compared with sham animals. Deconvolution analysis (mean +/- SEM) of plasma samples obtained every 10 minutes over 6 hours, and 14 to 16 days after second stage nephrectomy showed that NX rats had a longer GH t(1/2) (17.0 +/- 1.8 vs. 11.6 +/- 0.8 min), less GH mass secreted per burst (48 +/- 15 vs. 95 +/- 16 ng/ml/pulse), lower secretory pulse amplitude (1.9 +/- 0.5 vs. 5.8 +/- 0.9 ng/ml/min), and a reduced total GH secretion (240 +/- 69 vs. 400 +/- 56 ng/ml/6 hr) than SAL rats. Corresponding data were not significantly different between NX and SPF, or between SAL and SPF+ groups. In summary, stunted rats with chronic renal failure exhibit a prolonged GH t(1/2) and suppression of GH secretory pattern burst mass. Control data from rats with normal renal function suggest that the amplitude-specific depression of GH secretion may be attributed, at least in part, to chronic renal failure-associated calorie deficiency.     

Assessment of cerebral blood flow and CO2 reactivity after controlled cortical impact by perfusion magnetic resonance imaging using arterial spin-labeling in rats

We measured CBF and CO2 reactivity after traumatic brain injury (TBI) produced by controlled cortical impact (CCI) using magnetic resonance imaging (MRI) and spin-labeled carotid artery water protons as an endogenous tracer. Fourteen Sprague-Dawley rats divided into TBI (CCI; 4.02 +/- 0.14 m/s velocity; 2.5 mm deformation), sham, and control groups were studied 24 hours after TBI or surgery. Perfusion maps were generated during normocarbia (Paco2 30 to 40 mm Hg) and hypocarbia (PaCO2 15 to 25 mm Hg). During normocarbia, CBF was reduced within a cortical region of interest (ROI, injured versus contralateral) after TBI (200 +/- 82 versus 296 +/- 65 mL.100 g-1.min-1, P < 0.05). Within a contusion-enriched ROI, CBF was reduced after TBI (142 +/- 73 versus 280 +/- 64 mL.100 g-1.min-1, P < 0.05). Cerebral blood flow in the sham group was modestly reduced (212 +/- 112 versus 262 +/- 118 mL.100 g-1.min-1, P < 0.05). Also, TBI widened the distribution of CBF in injured and contralateral cortex. Hypocarbia reduced cortical CBF in control (48%), sham (45%), and TBI rats (48%) versus normocarbia, P < 0.05. In the contusion-enriched ROI, only controls showed a significant reduction in CBF, suggesting blunted CO2 reactivity in the sham and TBI group. CO2 reactivity was reduced in the sham (13%) and TBI (30%) groups within the cortical ROI (versus contralateral cortex). These values were increased twofold within the contusion-enriched ROI but were not statistically significant. After TBI, hypocarbia narrowed the CBF distribution in the injured cortex. We conclude that perfusion MRI using arterial spin-labeling is feasible for the serial, noninvasive measurement of CBF and CO2 reactivity in rats.     

Increase in dopamine release from the nucleus accumbens in response to feeding: a model to study interactions between drugs and naturally activated dopaminergic neurons in the rat brain

The aim of the present study was to investigate the interactions between the in vivo release of dopamine and certain drugs, during conditions of increased dopaminergic activity. Dopaminergic neurons in the nucleus accumbens were activated by feeding hungry rats. 48-96 h after implantation of a microdialysis probe 30 min food ingestion by hungry rats induced an immediate eating response that was accompanied with a reproducible and long-lasting increase in extracellular dopamine and 3,4-dihydroxyphenylacetic acid (DOPAC). The effect of various drugs (infused into the nucleus accumbens via the microdialysis probe), on the extracellular levels of dopamine and DOPAC were recorded, and the effect of eating was determined. Infusion of 5 mumol/l nomifensine and 3.4 mmol/l calcium increased dopamine release respectively 5.4 and 2-fold but did not modify the eating related increase in dopamine and DOPAC release. Infusion (1 mumol/l) as well as intraperitoneal administration (20 mg/kg) of sulpiride induced an increase in basal dopamine release to 220 and 195% of controls, respectively. Both routes of sulpiride pretreatment enhanced the eating related increase in extracellular dopamine and DOPAC. The results of the sulpiride experiments indicate that a behaviorally induced stimulation of dopamine release is modified by autoinhibition.     

Muscarinic receptor subtype involvement in brain cholinergic stimulation by intracerebroventricular neostigmine in sinoaortic denervated rats

1. The present studies evaluated the participation of central muscarinic receptors in the cardiovascular effects of centrally injected neostigmine, a quaternary anticholinesterase, in conscious, sham-operated rats and in sinoaortic denervated animals. 2. The dose-dependent pressor effect of neostigmine (0.1 to 1 microg i.c.v.) was greater in sinoaortic denervated rats than in sham-operated animals, but only a dose-dependent bradycardic effect was seen in sham-operated rats. 3. Doses of 3.3 nmol (i.c.v.) of both the M1 muscarinic antagonist, pirenzepine, and the M3 muscarinic antagonist, 4-DAMP, prevented the pressor response to 1 microg of neostigmine in sham-operated rats and in sinoaortic denervated animals; however, the M2 muscarinic antagonist, AF-DX116, partially blocked this response in sham-operated rats while failing to do so in sinoaortic denervated rats. In sham rats, doses of 3.3 nmol (i.c.v.) of both pirenzepine and 4-DAMP prevented the bradycardic response to 1 microg (i.c.v.) of neostigmine, whereas AF-DX116 induced a partial blockade. 4. 4-DAMP, at the dose of 0.3 nmol (i.c.v.), but not pirenzepine at the same dose, prevented the pressor effect of neostigmine (0.1 to 1 microg i.c.v.) in both groups of rats. Both muscarinic antagonists at this dose prevented the bradycardia elicited by the anticholinesterase (0.1 to 1 microg i.c.v.), but 4-DAMP showed a greater antagonistic action on this cardiac effect than pirenzepine. In sham-operated rats, i.c.v. injection of 0.3 nmol of AF-DX116 failed to modify the cardiovascular responses to 0.3 microg of neostigmine. 5. Results suggest mainly an involvement of brain M3-subtype muscarinic receptors in the cardiovascular effect of intracerebroventricular administration of anticholinesterase neostigmine in both groups of rats.     

Bacteraemia during the aplastic phase after allogeneic bone marrow transplantation is associated with early death from invasive fungal infection

OBJECTIVE: The main objective of this study was to evaluate the effect of switching from parenteral to enteral feeding on liver blood flow and propofol steady-state blood concentrations in patients in the intensive care unit (ICU). DESIGN AND PATIENTS: Steady-state blood concentrations of propofol were measured in eight ICU patients before (on days D -3, D -2, and D -1) and after (on days D + 1, D + 2, and D + 3) switching from parenteral to enteral feeding (on day DO). All patients received a continuous intravenous infusion of propofol (4.5 mg x kg(-1) x h(-1)) from several days before the start of the study, continuing throughout the experimental period. Hepatic blood flow was estimated by measuring steady-state D-sorbitol hepatic clearance. RESULTS: Hepatic blood flow was high and was not affected by switching from parenteral to enteral feeding: 33 +/- 8 ml x min(-1) x kg(-1) (mean +/- SD) and 33 +/- 10 ml min(-1) x kg(-1) on D -3 and D -1, respectively, as compared to 37 +/- 11 ml x min(-1) kg(-1) and 34 +/- 8 ml x min(-1) x kg(-1) on days D + 1 and D + 3, respectively. Systemic clearance of propofol was much higher than liver blood flow with average values on the six observation days ranging from 74.0 to 81.2 ml x min(-1) x kg(-1) and was not affected by switching from parenteral to enteral feeding. CONCLUSIONS: Liver blood flow and systemic clearance of propofol were not affected by switching from parenteral to enteral feeding in the eight ICU patients studied. Extrahepatic clearance accounted for at least two thirds of the overall systemic clearance of propofol.     

Epithelial removal with the excimer laser (laser-scrape) in photorefractive keratectomy retreatment

1. A study was made relating the involvement of alpha-adrenoceptors in the cardiovascular responses to intracerebroventricular (i.c.v.) injection of B-HT 920, a clonidine-type drug, in conscious sham-operated and sinoaortic-denervated rats. 2. Wistar rats were used, 7 days after the sham operation or sinoaortic denervation. For i.c.v. injection of drugs, a guide cannula had been previously implanted in the left lateral ventricle. 3. In sham-operated rats, cardiovascular responses to B-HT 920 (10-60 microg) were increased blood pressure and bradycardia; but, in sinoaortic-denervated rats, after the pressor response, a decrease in blood pressure also was seen. The responses to this agent were greater in sinoaortic-denervated rats than in sham-operated animals. Treatment with the alpha2-adrenoceptor antagonist yohimbine (30 microg), the imidazoline receptor antagonist idazoxan (15 microg) and the alpha1A-adrenoceptor antagonist 5-methylurapidil (15 microg) blocked the responses to B-HT 920 (30 microg). The alpha1-adrenoceptor antagonist prazosin (15 microg) and the alpha1B-adrenoceptor antagonist chloroethylclonidine (100 microg) did not modify the responses to agonist. 4. Sinoaortic denervation enhances the cardiovascular responses to B-HT 920. Moreover, the effects of i.c.v. administration of B-HT 920 could be mediated by several types of brain receptors: imidazoline receptors and alpha1A- and alpha2-adrenoceptors.     

Upregulation of atrial natriuretic peptide gene expression in remnant kidney of rats with reduced renal mass

Atrial natriuretic peptide (ANP) is synthesized in the kidney but its physiologic significance there is unclear. To determine whether renal expression of the ANP gene is regulated, renal ANP mRNA expression was assessed in remnant kidneys after 5/6 nephrectomy in Munich-Wistar rats. In normal sodium intake groups, ANP mRNA expression in the remnant kidney was significantly increased by 5.0 +/- 0.8-fold (n = 7, mean +/- SEM) at 4 d when compared with sham-operated controls (n = 6, all sham-operated groups) (*P < 0.001 by Scheffe's test) and by 28.3 +/- 5.1-fold at 14 d. This latter response was markedly diminished to 7.6 +/- 2.1-fold (n = 7, versus sham) in rats maintained on a low sodium diet. At 4 d, on the other hand, no significant downregulation was observed with dietary sodium restriction. Because natriuretic peptides have previously been shown by us to play a major role in the adaptive responses of remnant nephrons to renal mass ablation, these data suggest that ANP of renal origin may contribute to the overall mechanism for enhancing sodium excretion in the face of declining nephron number.