Effect of ventilation on sodium excretion in the anesthetized dog with unilateral renal denervation

We studied if the effect of mechanical ventilation induced to keep arterial blood gas values within normal physiological limits has any influence on renal sodium excretion in anesthetized dogs (n = 17) subjected to acute unilateral renal denervation. Compared to the control and the postcontrol periods, ventilation elevated arterial pO2 from 86 +/- 5 to 96 +/- 5 mmHg and blood pH from 7.37 +/- 0.02 to 7.41 +/- 0.01 while arterial pCO2 was decreased from 38 +/- 2 to 33 +/- 1 mmHg (p less than 0.05 in all cases). Compared to the innervated kidney urine flow, urinary sodium and potassium excretion from the denervated kidney were markedly elevated both during spontaneous respiration and during mechanical ventilation but GFR and cPAH were similar on the two sides. Ventilation decreased sodium excretion by the denervated kidney from 314 +/- 26 to 252 +/- 31 mumols/min/100 g k. w. (p less than 0.05). No other excretory changes were noted either in the innervated or in the denervated kidneys. Difference in sodium excretion between innervated and denervated kidneys was decreased from 209 +/- 19 to 126 +/- 20 mumole/min/100 g k. w. (p less than 0.001), due to the ventilation induced diminution of sodium excretion from the denervated kidney. It is concluded that mechanical ventilation of anesthetized dogs modifies sodium excretion, and this phenomenon can be demonstrated only in the denervated kidney.     

Supersensitivity to norepinephrine in chronically denervated kidneys: evidence for a postsynaptic effect

Denervation supersensitivity in chronically denervated kidneys increases renal responsiveness to increased plasma levels of norepinephrine. To determine whether this effect is caused by presynaptic (i.e., loss of uptake) or postsynaptic changes, we studied the effect of continuous infusion of norepinephrine (330 ng/min, i.v.) and methoxamine (4 micrograms/min, i.v.), an alpha 1-adrenergic agonist that is not taken up by nerve terminals, on renal function of innervated and denervated kidneys. Ganglionic blockade was used to eliminate reflex adjustments in the innervated kidney and mean arterial pressure was maintained at preganglionic blockade levels by an infusion of arginine vasopressin. With renal perfusion pressure controlled there was a significantly greater decrease in renal blood flow (-67 +/- 9 vs. -33 +/- 8%), glomerular filtration rate (-60 +/- 9 vs. -7 +/- 20%), urine flow (-61 +/- 7 vs. -24 +/- 11%), sodium excretion (-51 +/- 15 vs. -32 +/- 21%), and fractional excretion of sodium (-50 +/- 9 vs. -25 +/- 15%) from the denervated kidneys compared with the innervated kidneys during the infusion of norepinephrine. During the infusion of methoxamine there was a significantly greater decrease from the denervated compared with the innervated kidneys in renal blood flow (-54 +/- 10 vs. -30 +/- 14%), glomerular filtration rate (-51 +/- 11 vs. -19 +/- 17%), urine flow (-55 +/- 10 vs. -39 +/- 10%), sodium excretion (-70 +/- 9 vs. -59 +/- 11%), and fractional excretion of sodium (-53 +/- 10 vs. -41 +/- 10%).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effects of arachidonate on permeability and resistance distribution in canine lungs

In this study, 14 canine lung lobes were isolated and perfused with autologous blood at constant pressure (CP) or constant flow (CF). Pulmonary capillary pressure (Pc) was measured via venous occlusion or simultaneous arterial and venous occlusions. Arterial and venous pressures and blood flow were measured concurrently so that total pulmonary vascular resistance (RT) as well as pre- (Ra) and post- (Rv) capillary resistances could be calculated. In both CP and CF perfused lobes, 5-min arachidonic acid (AA) infusions (0.085 +/- 0.005 to 2.80 +/- 0.16 mg X min-1 X 100 g lung-1) increased RT, Rv, and Pc (P less than 0.05 at the highest dose), while Ra was not significantly altered and Ra/Rv fell (P less than 0.05 at the highest AA dose). In five CP-perfused lobes, the effect of AA infusion on the pulmonary capillary filtration coefficient (Kf,C) was also determined. Neither low-dose AA (0.167 +/- 0.033 mg X min-1 X 100 g-1) nor high-dose AA (1.35 +/- 0.39 mg X min-1 X 100 g-1) altered Kf,C from control values (0.19 +/- 0.02 ml X min-1 X cmH2O-1 X 100 g-1). The hemodynamic response to AA was attenuated by prior administration of indomethacin (n = 2). We conclude that AA infusion in blood-perfused canine lung lobes increased RT and Pc by increasing Rv and that microvascular permeability is unaltered by AA infusion.     

Lack of effect on human lipoprotein-triacylglycerol on the function of perfused rat kidney

We determined whether addition of human lipoprotein-TG to the perfusate for the isolated rat kidney would increase net Na+ reabsorption or maintain renal tissue K+ content. Rat kidneys (n = 6) were perfused for 75 min with a perfusate containing 6 g% of substrate-free albumin in Krebs-Ringer bicarbonate and a mixture of human chylomicrons and very low density lipoproteins (human lipoprotein-triacylglycerol (HL-TG]. Control kidneys (n = 6) were perfused in the substrate-limited state, i.e., without any exogenous substrates added to the perfusate. Means (n = 6) for function of control kidneys were GFR = 808 +/- 50 microliter g-1 X min-1; %T-Na+ = 63.3 +/- 1.3%. A significant loss of tissue K+ occurred: tissue K+ remaining after 75 min of perfusion = 79.1 +/- 1.9%. Although kidney tissue contains lipoprotein lipase, HL-TG (n = 6) did not increase %Na+ reabsorption (64.3 +/- 2.6%) or maintain tissue K+ content (80.6 +/- 2.0%). Therefore, the TG might have been hydrolyzed and taken up for biosynthesis, the rat kidney lipoprotein lipase might have been inactive, or the rat kidney might not use lipoprotein-TG for biosynthesis or oxidation.     

Levels of Catechols in Epileptogenic and Nonepileptogenic Regions of the Human Brain

Recent reports about tyrosine hydroxylase and alpha 1-adrenoceptors in epileptic foci have suggested increased regional catecholaminergic activity, which may serve a compensatory, inhibitory role. We measured levels of catechols, including the precursor 3,4-dihydroxyphenylalanine (DOPA) and the catecholamines dopamine (DA) and norepinephrine (NE), in surgically removed foci identified by electrocorticography and in nonepileptogenic sites from 23 patients with intractable temporal lobe epilepsy. The following values (mean +/- 1 SD) were obtained: DOPA = 142 +/- 60 ng/g of protein in the focus vs. 115 +/- 39 ng/g in the nonfocus (p less than 0.01); DA = 168 +/- 85 vs. 106 +/- 54 ng/g (p less than 0.001); and NE = 267 +/- 117 vs. 181 +/- 80 ng/g (p less than 0.001). The results are consistent with increased catecholaminergic activity in epileptic foci.     

脑室内注射高张盐水抑制近曲小管对水和钠的重吸收

实验在麻醉大鼠上进行。用锂清除率为指标观察脑室内注射高张盐水对近曲小管重吸收水和钠的影响。在切断单侧肾神经的动物中,脑室内注射高张盐水后的锂清除率与肾小球滤过率比值在去神经侧肾脏从0.37±0.04增加至0.51±0.05(P<0.01);神经完好侧肾脏则从0.26±0.03增加至0.31±0.04(P<0.05);双侧肾脏的肾小球滤过率、尿量、尿钠和尿钾量均增加,且去肾神经肾脏的增加幅度高于肾神经完好肾脏。在肾小管微穿刺实验中,脑室内注射高张盐水后,近曲小管末段小管液流量从24.42±1.84nl/min增加至31.86±3.09nl/min(P<0.01),小管液的渗透压无显著变化。以上实验结果表明,脑室内注射高张盐水引起的利尿、尿钠增多反应与肾小球滤过率增加和近曲小管对水、钠重吸收减少有关,体液因素在该反应中可能起主要作用。     

Albumin attenuation of oleic acid edema in dog lung depleted of blood components

Circulating fatty acids are normally transported principally bound to serum albumin. We examined whether administering oleic acid (OA) in a concentrated albumin solution would attenuate its edemogenic potential in the isolated dog lung lobe perfused with a solution nearly depleted of blood cellular and protein components. The isolated ventilated lower left lobe (LLL) was perfused (7.3 +/- 0.6 ml X min-1 X g LLL-1) with a balanced salt solution containing 6% dextran and approximately 10% serum (vol/vol). Hourly weight gain, net LLL weight gain, and wet-to-dry weight ratio (W/D) were used as indices of extravascular lung fluid changes. Group I lobes (n = 5) were given saline, whereas both group II (n = 5) and III (n = 5) lobes were administered 1 microliter OA/kg body wt. The OA was incubated with 5 ml of albumin solution containing approximately 640 mg of bovine fatty acid-free albumin before infusion into group III lobes. Group I gained weight at rate of 10.8 +/- 0.5 g X h-1 X 100 g LLL-1 after saline, whereas group II exhibited a greater (P less than 0.005) rate of weight gain of 42 +/- 13 after OA. Group III weight gain of 8.4 +/- 0.5 g X h-1 X 100 g LLL-1 was not different (P greater than 0.05) from group I but was lower (P less than 0.005) than group II.(ABSTRACT TRUNCATED AT 250 WORDS)     

Mitochondrial and extramitochondrial Ca2+ pools in the perfused rat liver. Mitochondria are not the origin of calcium mobilized by vasopressin

A nondisruptive technique developed by Bellomo et al. (Bellomo, G., Jewell, S. A., Thor, H., and Orrenius, S. (1982) Proc. Natl. Acad. Sci. U.S.A. 79, 6842-6846) has been used to examine the distribution of calcium ions between mitochondrial and extramitochondrial compartments in the perfused rat liver. The amount of calcium released by the uncoupler 2,4-dinitrophenol from the mitochondrial compartment was 19 +/- 2 nmol X g-1, wet weight, which is equivalent to a total calcium concentration of 3.5 X 10(-4) M in the mitochondria and is by several orders of magnitude smaller than the concentration thought to be present in these organelles. The amount of calcium released from the liver in the presence of the divalent cation ionophore A 23187 was 96 +/- 7 nmol X g-1, wet weight, which is of the same order of magnitude as the amount released by the calcium-dependent hormone vasopressin (97 +/- 11 nmol X g-1, wet weight). Experiments with different sequential combinations of hormone with uncoupler or ionophore reveal that in the perfused liver, in contrast to isolated hepatocytes or isolated mitochondria, the amount of calcium attributable to the mitochondria is too small to account for the calcium released during hormonal stimulation. Consequently extramitochondrial calcium stores are the main source of cellular calcium mobilized under this condition. In addition these findings imply that in the liver several mitochondrial enzymes, e.g. alpha-oxoglutarate dehydrogenase, can be effectively regulated by calcium and that the role of mitochondria in buffering the cytosolic free calcium in vivo has to be reconsidered.     

Renal metabolism and urinary excretion of platelet-activating factor in the rat

The origin of platelet-activating factor (PAF) in the urine remains ill defined. The present study documents that [3H]PAF (3.5 mu Ci) injected into the renal artery of isolated control rat kidney preparations perfused at constant pressure with a cell-free medium containing 1% bovine serum albumin (BSA) was excreted in negligible amounts (0.034%) in the urine, whereas 6% was retained by the kidney. When kidneys were perfused with a BSA-free medium, 0.029 and 71% of the total radioactivity added to the perfusate was recovered in the urine and in the renal tissue, respectively. [3H]PAF urine excretion in proteinuric kidneys from adriamycin-treated rats was still negligible (0.015%). Analysis of the renal tissue-retained radioactivity in control and proteinuric kidneys perfused with 1% BSA indicated metabolism into long chain acyl-sn-glycero-3-phosphorylcholine species, lyso-PAF, glycerols, and intact PAF. Thin layer chromatography analysis of [3H]glycerol fraction in these renal extracts showed two major components comigrating with 1-O-alkylglycerol and 1-O-alkyl-2-fatty acylglycerol. Isolated proximal tubules, but not glomeruli from nephrotic rats exposed to increasing concentrations of BSA (0-4%), had a higher PAF uptake than control tubules for BSA concentrations ranging from 0 to 0.1%. Our findings in the isolated perfused kidneys indicate that, in normal conditions, circulating PAF is excreted in the urine in negligible amounts and that the altered glomerular permeability to proteins does not affect this excretion rate. Moreover, analysis of renal tissue radioactivity documented that the renal metabolism of PAF is comparable in control and nephrotic kidneys.     

Microvascular albumin permeability in isolated perfused lung: effects of EDTA

We examined the effects of decreases in perfusate concentrations of calcium and magnesium on the pulmonary vascular permeability in the isolated perfused rabbit lung. The albumin permeability-surface area product (PS) and the albumin reflection coefficient (sigma) were determined in the same lung using 125I- and 131I-labeled albumin tracers. Decreases in vascular Ca2+ and Mg2+ concentrations were induced by adding ethylenediaminetetraacetic acid (EDTA) to the perfusate. Decreases in the concentration of these cations resulted in an increase in the PS from a control value of 1.18 +/- 0.13 X 10(-3) to 7.69 +/- 0.75 X 10(-3) cm3 X min-1 X g wet lung wt-1 and a decrease in the sigma from 0.96 +/- 0.01 to 0.74 +/- 0.02. The decrease in sigma suggests an increase in the calculated equivalent pore radius from 44 to 63 A. The results indicate that Ca2+ and Mg2+ play a role in the maintenance of normal pulmonary vascular permeability to proteins.     

Endogenous triacylglycerol utilization by rat skeletal muscle during tetanic stimulation

An isolated perfused rat hindquarter preparation was used to examine the utilization of endogenous triacylglycerol (TG) during 20 min of electrical stimulation. The sciatic nerve was stimulated with maximal tetanic trains at 0.5 Hz. The isometric tension generated by the gastrocnemius-plantaris-soleus muscle group was recorded, and muscle samples were taken pre- and poststimulation. Twenty minutes of stimulation significantly reduced endogenous TG from 6.78 +/- 0.84 to 4.64 +/- 0.64 mumol X g dry wt-1 (32%) in the red gastrocnemius muscle and from 7.70 +/- 0.61 to 6.66 +/- 0.80 mumol X g dry wt-1 (13.5%) in the plantaris muscle. Although TG content decreased by 16% in the soleus (28.2 +/- 5.0 to 23.8 +/- 4.4 mumol X g-1), the change was not significant. Stimulation had no effect on white gastrocnemius TG concentration (6.84 +/- 1.22 to 6.25 +/- 1.41 mumol X g-1). Thus oxidation of TG occurred primarily in muscles with a large proportion of fast-twitch oxidative-glycolytic fibers. Calculations from measurements of muscle energy stores and fuel uptake indicated that up to 62% of the aerobic energy was provided by endogenous TG. Carbohydrate oxidation contributed up to 28% and the remaining 10% may be accounted for by the oxidation of exogenous free fatty acids originating in the perfusate or from hindquarter adipose tissue. The magnitude of the fall in TG concentration in a given muscle was inversely related to the fall in glycogen concentration.     

Permeability characteristics of isolated perfused rat lungs

We examined the factors that influence the permeability characteristics of isolated perfused rat lungs and compared the ex vivo permeability-surface area product (PS) with that obtained in vivo. In lungs perfused for 20 min with homologous blood or a physiological salt solution (PSS) containing 4 g/100 ml albumin, mean PS values, obtained by the single-sample method of Kern et al. [Am. J. Physiol. 245 (Heart Circ. Physiol. 14): H229-H236, 1983], were 9.9 +/- 0.6 (SE) and 6.8 +/- 0.3 cm3.min-1.g wet lung-1.10(-2), respectively. These values were similar to lung PS obtained in intact rats (7.7 +/- 0.4 cm3.min-1.g wet lung-1.10(-2). In perfused lungs, PS values were influenced by the perfusate albumin concentration, the length of perfusion time, and the degree of vascular recruitment. Twenty minutes after lung isolation, PS was 126% higher in lungs perfused with albumin-free PSS containing Ficoll than in lungs perfused with albumin-PSS. Moreover, PS in Ficoll-PSS-perfused lungs increased even higher after 2 h of perfusion, and this time-dependent increase in PS was attenuated by addition of 0.1 g/100 ml albumin to the perfusate. Two hours of ex vivo ventilation with hypoxic (0 or 3% 0(2)) or hyperoxic (95% 0(2)) gas mixture did not affect PS values in perfused lungs. However, PS was elevated in lungs perfused ex vivo with protamine, which causes endothelial cell injury, or in lungs from rats exposed in vivo to human recombinant tumor necrosis factor.(ABSTRACT TRUNCATED AT 250 WORDS)     

Cerebral blood flow in intoxicated newborn piglets

Ethanol exposure in the neonatal period causes impaired brain growth and altered adult behaviour in rats. One possible mechanism may be altered cerebral perfusion caused by ethanol intoxication. We assessed the effects of ethanol on cerebral blood flow and its autoregulation in 2-day-old piglets. Piglets received ethanol (1.4 g/kg) or an equivalent volume of dextrose 5% in water over 30 min. One hour later, cerebral blood flow was measured using the microsphere technique at resting, elevated, and decreased mean arterial blood pressure. Ethanol-treated piglets had total cerebral blood flows of 88 +/- 14, 82 +/- 10, and 82 +/- 12 mL X 100 g-1 X min-1 (mean +/- SE) at mean arterial blood pressures of 12.4 +/- 1.1, 15.7 +/- 1.5, and 8.2 +/- 0.9 kPa. Corresponding values in control piglets were 82 +/- 14, 78 +/- 4, and 82 +/- 7 mL X 100 g-1 X min-1 at mean arterial blood pressures of 10.5 +/- 1.5, 14.0 +/- 1.2, and 7.7 +/- 1.1 kPa. At resting arterial blood pressures, regional blood flows to basal ganglia, cortex, brainstem, and cerebellum in ethanol-treated piglets were 123 +/- 21, 90 +/- 16, 94 +/- 17, and 77 +/- 12 mL X 100 g-1 X min-1, respectively. Corresponding regional blood flows for the control piglets were 118 +/- 16, 85 +/- 15, 76 +/- 16, and 76 +/- 16 mL X 100 g-1 X min-1. Blood flow to basal ganglia was greater than to other brain regions in both ethanol-treated and control piglets (P less than 0.01).(ABSTRACT TRUNCATED AT 250 WORDS)     

Effect of increased Hb-O2 affinity on VO2max at constant O2 delivery in dog muscle in situ

We investigated the effect of increasing hemoglobin- (Hb) O2 affinity on muscle maximal O2 uptake (VO2max) while muscle blood flow, [Hb], HbO2 saturation, and thus O2 delivery (muscle blood flow X arterial O2 content) to the working muscle were kept unchanged from control. VO2max was measured in isolated in situ canine gastrocnemius working maximally (isometric tetanic contractions). The muscles were pump perfused, in alternating order, with either normal blood [O2 half-saturation pressure of hemoglobin (P50) = 32.1 +/- 0.5 (SE) Torr] or blood from dogs that had been fed sodium cyanate (150 mg.kg-1.day-1) for 3-4 wk (P50 = 23.2 +/- 0.9). In both conditions (n = 8) arterial PO2 was set at approximately 200 Torr to fully saturate arterial blood, which thereby produced the same arterial O2 contents, and muscle blood flow was set at 106 ml.100 g-1.min-1, so that O2 delivery in both conditions was the same. VO2max was 11.8 +/- 1.0 ml.min-1.100 g-1 when perfused with the normal blood (control) and was reduced by 17% to 9.8 +/- 0.7 ml.min-1.100 g-1 when perfused with the low-P50 blood (P less than 0.01). Mean muscle effluent venous PO2 was also significantly less (26 +/- 3 vs. 30 +/- 2 Torr; P less than 0.01) in the low-P50 condition, as was an estimate of the capillary driving pressure for O2 diffusion, the mean capillary PO2 (45 +/- 3 vs. 51 +/- 2 Torr). However, the estimated muscle O2 diffusing capacity was not different between conditions.(ABSTRACT TRUNCATED AT 250 WORDS)     

Dependence of the parameters of microcirculation and lymph flow in the liver on the value of venous pressure

In experiments on cats the perfusion (at a constant flow and controlled venous outflow) of haemodynamic isolated liver was carried out. It was shown that at the levels of venous pressure in the liver 0, 2, and 4 mm Hg, the lymph flow (22.8 +/- 3.5, 41.8 +/- 5.7 and 57.6 +/- 8.6 mkl.min-1.100 g-1, respectively) was depended on the value of hydrostatic pressures in the sinusoids (1.4 +/- 0.1, 3.3 +/- 0.1, and 5.4 +/- 0.1 mm Hg, respectively) and did not depend on the value of sinusoidal filtration coefficient (0.421 +/- 0.029, 0.473 +/- 0.036, and 0.474 +/- 0.034 ml.min-1.mm Hg-1.100 g-1, respectively).     

The membrane attack complex in complement-mediated glomerular epithelial cell injury: formation and stability of C5b-9 and C5b-7 in rat membranous nephropathy

Using a model of rat membranous nephropathy (MN), we examined the relationship between the development of glomerular epithelial cell injury and the formation and stability of the membrane attack complex (MAC) of complement. Isolated rat kidneys were perfused with buffered bovine albumin (BSA) or various plasmas (complement source). Kidneys containing nephritogenic amounts of complement-fixing sheep antibody to glomerular epithelial antigens (aFx1A) perfused with BSA (n = 5), and normal kidneys perfused with normal human plasma in BSA (50% v/v, n = 6) excreted 0.30 +/- 0.02 mg protein/min/g during 90 min perfusion (control groups). When normal plasma was added to the perfusate of aFx1A kidneys at concentrations of 12.5, 25, and 50% v/v, protein excretion rose in a time- and concentration-dependent manner. Perfusions with 25% plasma resulted in baseline proteinuria from 0 to 20 min that increased to 2.8 +/- 0.9 mg/min/g at 20 to 40 min and 8.6 +/- 2.1 at 40 to 60 min (n = 4, p less than 0.01 vs control groups). Removal of plasma at 20 min did not prevent this rise in protein excretion (3.9 +/- 2.4 and 5.8 +/- 2.6 mg/min/g at 30 to 40 and 55 to 65 min respectively, p less than 0.01, n = 4). Perfusion of aFx1A kidneys with C8-deficient (C8D) human plasma (25% v/v, n = 4) or C6D rabbit serum (25% v/v, n = 2) independently produced low levels of proteinuria comparable with BSA, but in combination, the two reagents restored enhanced protein excretion (n = 2). In aFx1A kidneys containing C5b-7, addition of C8 and C9 (C6D serum) after intervals of 20, 60, or 90 min immediately reconstituted heavy proteinuria. Thus, the magnitude of MAC-induced glomerular epithelial injury in rat MN is related to the complement dose. Altered glomerular permeability is delayed with respect to the onset of complement activation. Once sufficient C5b-9 is formed, proteinuria can develop despite cessation of new MAC assembly, implying that C5b-9 persists after formation. Moreover, the C5b-7 MAC intermediate is not eliminated rapidly in this model.     

Separate effects of ischemia and reperfusion on vascular permeability in ventilated ferret lungs.

In systemic organs, ischemia-reperfusion injury is thought to occur during reperfusion, when oxygen is reintroduced to hypoxic ischemic tissue. In contrast, the ventilated lung may be more susceptible to injury during ischemia, before reperfusion, because oxygen tension will be high during ischemia and decrease with reperfusion. To evaluate this possibility, we compared the effects of hyperoxic ischemia alone and hyperoxic ischemia with normoxic reperfusion on vascular permeability in isolated ferret lungs. Permeability was estimated by measurement of filtration coefficient (Kf) and osmotic reflection coefficient for albumin (sigma alb), using methods that did not require reperfusion to make these measurements. Kf and sigma alb in control lungs (n = 5), which were ventilated with 14% O2-5% CO2 after minimal (15 +/- 1 min) ischemia, averaged 0.033 +/- 0.004 g.min-1.mmHg-1.100 g-1 and 0.69 +/- 0.07, respectively. These values did not differ from those reported in normal in vivo lungs of other species. The effects of short (54 +/- 9 min, n = 10) and long (180 min, n = 7) ischemia were evaluated in lungs ventilated with 95% O2-5% CO2. Kf and sigma alb did not change after short ischemia (Kf = 0.051 +/- 0.006 g.min-1.mmHg-1.100 g-1, sigma alb = 0.69 +/- 0.07) but increased significantly after long ischemia (Kf = 0.233 +/- 0.049 g.min-1 x mmHg-1 x 100 g-1, sigma alb = 0.36 +/- 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)     

Adenine nucleotide synthesis from inosine during normoxia and after ischaemia in the isolated perfused rat heart

[14C]inosine in a range of concentrations of 20 microM to 1 mM was administered to the isolated perfused rat heart for 30 min. The incorporation of the nucleoside into myocardial adenine nucleotides increased for extracellular concentrations of the precursor up to 50 microM, reaching a plateau at 60 nmol . g-1 X 30 min-1 with concentrations ranging between 50 and 200 microM. The supply of 500 microM and 1 mM of inosine induced a further increase in cardiac adenine nucleotide synthesis to about 200 nmol . g-1 X 30 min-1. When supplied during low flow ischaemia (0.5 mL . min-1, 30 min.), 1 mM of inosine protected the heart against ATP degradation, while 100 microM of inosine was inefficacious. In the presence of 1 mM of inosine on reperfusion the adenine nucleotide content of the heart was similar to that observed in the absence of the nucleoside. The incorporation of [14C]inosine into adenine nucleotides was, in this last condition, below the value measured before ischaemia. Inosine administration was effective in protecting the heart against ischaemic breakdown of glycogen and favoured postischaemic restoration of glycogen stores.     

Catecholamines in larvae and juveniles of the prosobranch gastropod, Crepidula fornicata

We investigated roles of catecholamines in metamorphosis of the prosobranch gastropod, Crepidula fornicata. Levels of DOPA, norepinephrine (NE) and dopamine (DA) were measured by high-pressure liquid chromatography (HPLC) in competent larvae and juvenile siblings that metamorphosed in response to the natural adult-derived cue or to elevated K+. Competent larvae contained 1.58 +/- 0.26 (S.E.M.) x 10(-2) pmol DOPA, 0.91 +/- 0.45 x 10(-2) pmol NE, and 0.290 +/- 0.087 pmol DA (mean values per microg total protein, n = 4 batches of larvae). Levels of DA per individual were not different between larvae and juvenile siblings; levels of NE were higher in juveniles. The tyrosine hydroxylase (TH) inhibitor alpha-methyl-DL-m-tyrosine (alpha-MMT) depleted DOPA and DA to approximately half of control values without affecting levels of NE. Depletion of DOPA and DA was accompanied by inhibition of metamorphosis in response to the natural cue but not to elevated K+. The dopamine-beta-hydroxylase inhibitor diethyldithiocarbamate (DDTC) induced high frequencies of metamorphosis at concentrations of 0.1-10 microM. In juveniles induced by 10 microM DDTC, levels of both NE and DA averaged approximately 80% of those in control larvae. Catecholamines may function as endogenous regulators of metamorphosis in C. fornicata.     

Renal function studies in an experimental model of papillary necrosis in the rat

Twenty four hours after i.v. injection of bromoethylamine-hydrobromide (BEA) in rats, a uniform papillary necrosis is observed. The present study investigates the renal functional and the papillary haemodynamics in response to acute volume expansion (12% of body weight) in this model. Renal function studies were performed in hydropenic and volume expanded sham- or BEA-injected rats. In hydropenic normal animals a GFR of 1.97 +/- 0.14 ml/min, an urinary osmolarity (UOsm) of 1 011 +/- 94.5 mOsm/kg and a fractional sodium excretion (FENa) of 0.18 +/- 0.026% were obtained. In contrast, BEA-treated hydropenic animals showed a lower GFR (1.16 +/- 0.14 ml/min), UOsm (469 +/- 30.31 mOsm/kg) and a higher FENa (0.37 +/- 0.06%). In volume expansion a similar UOsm and FENa were obtained in both groups. The papillary plasma flow (PPF) was measured in each of the experimental groups by the albumin accumulation technique. The mean value in hydropenic normal animals was 50.65 +/- 2.12 m 100 g-1 min-1 and increased to 66.02 +/- 2.00 ml 100 g-1 min-1 after volume expansion (P less than 0.001). In BEA rats the PPF was 58.86 +/- 2.33 ml 100 g-1 min-1 in hydropenia (P less than 0.01 vs. control animals) and remained unchanged after volume expansion. Thus, during hydropenia, BEA-induced papillary necrosis results with a salt wasting state and an urinary concentration defect. After volume expansion no disturbance in sodium excretion capacity was observed. These results are compatible with the nephron-heterogeneity concept in the regulation of sodium excretion. The histological lesions cannot be explained by a decreased renal papillary plasma flow.