The tubulo-glomerular feedback mechanism — a determinant for the autoregulation of the glomerular filtration rate in superficial and juxtamedullary nephrons

Summary The intrinsic myogenic hypothesis and the tubuloglomerular feedback mechanism (TGF) give the presently most cherished explanation to the autoregulation of renal blood flow and glomerular filtration rate. A series of experiments was performed on young, normohydrated rats in order to evaluate the importance of TGF as an autoregulatory factor of the single nephron glomerular filtration rate (SNGFR) in superficial and juxtamedullary nephron populations. Micropuncture techniques were applied to tubular structures of the renal surface and on the papilla for the measurement of hydrostatic pressures and SNGFR. The SNGFR was also measured with a modified Hanssen technique. A TV-technique was used to record the urine free flow rate in the loop of Henle.The net driving forces for glomerular filtration at the afferent end of the glomerular capillaries were estimated to be 19 and 47 mm Hg for superficial and juxtamedullary nephrons respectively, when the urine flow at the macula densa was zero. The SNGFR of the two nephron populations amounted to 29.6 and 84.1 nl·min^–1·g^–1 K.W., as measured with the micropuncture technique. With a modified Hanssen technique the corresponding values were 25.8 and 27.7 nl·min^–1. g^–1 K.W. (kidney weight).The SNGFR was found to be well autoregulated when the urine flow at the macula densa was intact, but not when the urine flow was interrupted.The flow rate in the loop of Henle was in free flow conditions 7.3 nl·min^–1·g^–1 K.W. which shall be compared with 19.2 nl·min^–1·g^–1 K.W. when the urine flow to the macula densa was zero.We conclude that SNGFR is mainly autoregulated by the TGF-mechanism in young, normohydrated rats at lower arterial pressures. In normal conditions TGF is highly activated for juxtamedullary nephrons, but not for the superficial ones. The high urine flow rate in the loop of Henle at reduced flow rates at the macula densa may invalidate the use of loop blockade in studies of water and solute transfer across the loop walls.     

Effect of exercise training on aortic collagen content in spontaneously hypertensive rats (SHR)

Summary We investigated the effects of exercise training on the amount of aortic collagen and systolic blood pressure in spontaneously hypertensive rats (SHR). Ten-week old SHR were trained either by forced treadmill running (26.8 m·min^–1 h·day^–1, five times a week, 0% incline) or by voluntary running in revolving wheels (7,800 m·day^–1 at peak) for 8 weeks. Succinate dehydrogenase (SDH) activity measured as a marker of an endurance training effect was 13% higher (P<0.01) in the soleus of forced-exercised animals than in that of sedentary ones. (6.56±0.17 mol·g^–1·min^–1; mean ± SEM), whereas SDH activity in that of voluntarily-exercised group was found to be at the same level as in sedentary animals. The systolic blood pressure after training increased by 26.4 in sedentary, 21.1 in voluntarily-exercised, and 33.9 mm Hg in forced-exercised rats, when compared with the value of each group at the beginning of the training programm. A significant difference was observed in the increment of blood pressure only between the voluntarily- and forced-exercised groups (P<0.05). The amount of aortic collagen in voluntarily-trained rats (96.5±2.0 mg·g tissue^–1, 39.8±0.7 mg·100 mg protein^–1) was significantly less than that in forced-trained rats (P<0.05). These results suggest that voluntary, mild exercise training may be more effective in the reduction of collagen accumulation in the aorta associated with the suppression of blood pressure increase than forced, vigorous exercise training in SHR.     

Limb vasodilatory capacity and venous capacitance of trained runners and untrained males

Aerobically trained athletes possess enhanced vasodilatory capacity and venous capacitance in their exercising muscles. However, whether they also possess these characteristics in their non-specific exercising muscles is undetermined. This study examined vasodilatory capacity and venous capacitance of specific (legs) and non-specific exercising muscles (arms) of ten trained runners and ten active but untrained males aged 18–35 years. Venous occlusion plethysmography determined baseline and peak blood flow after 5 min of reactive hyperaemia. Forearm and leg venous capacitance were determined as the difference between baseline and 2 min of venous occlusion at 50 mmHg. During reactive hyperaemia, trained runners had higher leg (48.4±5.3 ml·100 ml tissue^–1·min^–1) and arm (40.8±2.1 ml·100 ml tissue^–1·min^–1) vasodilatory capacity compared to the untrained (leg: 37.3±2.5 ml·100 ml tissue^–1·min^–1; arm: 34.2±2.2 ml·100 ml tissue^–1·min^–1; P<0.05), and higher calf vascular conductance (0.51±0.06 ml·100 ml tissue^–1·min^–1·mmHg^–1 versus 0.35±0.03 ml·100 ml tissue^–1·min^–1·mmHg^–1; P<0.05). The trained also had higher venous capacitance in both arms (3.5±0.2 ml 100·ml^–1) and legs (4.8±0.1 ml·100 ml^–1) compared to the untrained (3.0±0.2 ml 100·ml^–1; 4.2±0.2 ml·100 ml^–1; P<0.05). These findings show that vasculature adaptations to running occur in both specific and non-specific exercising muscles.     

The cause of a depressed glomerular filtration rate after an ischaemic insult: whole kidney and superficial nephron study in the dog

Twenty-four hours after 90 min clamping of the left renal artery in dogs, the glomerular filtration rate (GFR) was decreased in the whole kidney (0.34 ml.min^–1g KW^–1 [KW=Kidney weight] vs 0.64 in contralateral unclamped kidney) just as in the single nephron (SNGFR, 19.7 vs 51.8 nl.min^–1). Renal blood flow (RBF) did not change; single nephron glomerular blood flow (SNGBF) was decreased by 9% only. After injection of Lissamine green into the renal artery, brief diffuse tinting of the whole kidney surface was observed. Thereafter, patchy coloration — corresponding to passage of the dye through patent tubuli — took place in approximately one-quarter to one-third of the kidney surface. Micropuncture measurements were carried out in these areas.The values of hydraulic pressure in peritubular capillaries and proximal convolutions were not different from those found in controls; directly measured glomerular capillary pressure was decreased (48.7 vs 59.5 mmHg). The ultrafiltration coefficient(K _f) was significantly depressed (2.7 vs 3.8 mmHg.nl^–1.min). Total kidney and arteriolar resistances remained unchanged but afferent resistance (R _A) was elevated (11%) and efferent resistance (R _E) was lowered (23%) compared with those of controls. Ninetyseven percent of proximally microinjected ³H-inulin was recovered from the control kidney but only 85 % from the kidney rendered ischaemic. In conclusion, the typical findings at 24 h after 90 min ischaemia are low GFR and SNGFR with normal RBF and almost normal superficial SNGBF values. This phenomenon is mainly due to a decrease in K _f and a decrease in R _E with a simultaneous increase in R _A; back-leak through damaged tubuli seems to play only a minor role.     

Micropuncture studies on the filtration rate of single superficial and juxtamedullary glomeruli in the rat kidney

Summary Single nephron filtration rates of superficial and juxtamedullary nephrons were determined in high and low sodium rats. Single nephron GFR was calculated from TF/P inulin and tubular flow rate in superficial nephrons and single juxtamedullary GFR from corresponding data in long loops of Henle. In low sodium rats superficial nephron GFR was 23.5±6.4 (SD)×10^–6 ml/min×g KW, juxtamedullary nephron GFR was 58.2±13.6 and total kidney GFR (C _In) was 0.94±0.16 ml/min×g KW. Using these single nephron values, total kidney GFR and a total number of 30,000 glomeruli per kidney, the number of superficial and juxtamedullary glomeruli was calculated to be 23,267 and 6,733, respectively. During high sodium diet superficial nephron GFR increased to 38.1±11.3 and single juxtamedullary GFR decreased to 16.5±6.6, total kidney GFR increasing to 1.01±0.24. Calculation again revealed the same distribution of the two nephron types. End-proximal TF/P inulin in superficial nephrons was 2.36±0.36 in low sodium and 2.31±0.28 in high sodium rats. Loops of Henle TF/P inulin and intratubular flow rate were inversely related: the highest TF/P inulin values and lowest intratubular flow rates were found in the descending limb. These data quantify the distribution of superficial and juxtamedullary nephrons on a functional basis and suggest a mechanism by which the kidney adjusts sodium excretion by altering the contribution of each nephron type to total kidney GFR.Supported by the Deutsche Forschungsgemeinschaft and the U.S. Department of the Army, through its European Research Office.     

Pathways of phosphate transport in chick jejunum

The effect of vitamin D₃ on intestinal phosphate (P_i) absorption was studied in everted sacs prepared from jejunum of either vitamin D-deficient (–D) or vitamin D-replete (+D) chicks. Vitamin D₃ stimulates the maximal velocity (V _max) of a mucosal active P_i transport mechanism from 125 to 314 nmol·min^–1·g^–1 tissue.K _m of this process remains virtually unchanged (–D: 0.15 mmol·l^–1; + D: 0.18 mmol·l^–1).Active P_i entry into the epithelium depends on extracellular Na⁺. Reduction of buffer Na⁺ reducesV _max in the + D group to 182 nmol·min^–1·g^–1 tissue but has no significant effect in the –D animals (V _max=105 nmol·min^–1·g^–1 tissue). In this group, the predominant effect of Na⁺ substitution is a shift ofK _m to 1.13 mmol·l^–1, whileK _m in the +D group is changed only to 0.53 mmol·l^–1.Transeptithelial P_i transport in the + D group involves the mucosal phosphate pump and hence an intracellular pathway, proceeding at a rate of 48 nmol·min^–1·g^–1 tissue. This is in contrast to –D P_i transfer (8 nmol·l^–1·g^–1 tissue) which is by a diffusional, Na⁺-insensitive, and presumably paracellular pathway.Transepithelial calcium transport (–D: 3.3 nmol·min^–1·g^–1; + D: 7.6 nmol·min^–1·g^–1 tissue) does not require the presence of extracellular Na⁺ and apparently involves pathways different from those of the P_i absorptive system.Presented in part at the Annual Meeting of the Austrian Biochemical Society, Salzburg, September 1978     

Effect of dehydration and rapid rehydration on renal function and on plasma renin and aldosterone levels in the black Bedouin goat

Bedouin goats in the extreme deserts of the Middle East are regularly subjected to severe dehydration and possess a capacity to rapidly rehydrate by drinking large volumes of water. Urine flow, glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) in the fully hydrated animals amounted to 0.74±0.4 ml · min^–1, 76±29 ml · min^–1 and 344±146 ml · min^–1 respectively. In goats that were dehydrated to a loss of about 30% of their initial body weight, urine flow dropped to 24% of the value recorded in the hydrated animals and GFR and ERPF dropped to half their level recorded in the hydrated phase. Na and K⁺ excretion decreased in the water depleted goats and further decrease was recorded following drinking. Following drinking the urine flow, GFR and ERPF of the recently rehydrated goats dropped to below the rates recorded in the dehydrated animals. During the 3 h of the continuous recording that followed the drinking, all three rates did not exceed the predrinking level. Plasma renin activity amounted to 0.37±0.32 ng AI·ml^–1·h^–1 in the hydrated animals. In dehydrated ones it amounted to 4.8±2.8 ng AI·ml^–1·h^–1 and a further increase was recorded following drinking. Aldosterone in the hydrated goats was 5.5±4.3 ng% and increased to 13.9±2.3 ng% in the dehydrated animal and amounted to 20.1±5.5 ng% 2 h following drinking. It is concluded that the kidney in the Bedouin goat plays a major role in conserving both water and solutes, not only when deprived of water but also following its rapid rehydration.     

Valine oxidation in the rat medullary thick ascending limb

In the kidney, a branched-chain amino acid transferase (BCAAT) activity has been localized mainly in the medullary thick ascending limb (MTAL) of the rat nephron. BCAAT is the first enzyme involved in the metabolic pathway of the three branched-chain amino acids (BCAA): leucine, isoleucine and valine. The present work has been designed to study valine catabolism. Valine and leucine oxidation in MTAL were compared by measuring the rate of ¹⁴CO₂ produced when these substrates were incubated as sole substrates at a final concentration of 1 mM. Since glucose is also metabolized in MTAL, valine and leucine oxidation were quantified also in the presence of glucose (1 mM). The results show that: (1) valine oxidation was greater than that of leucine (63.0±4.7 vs 39.7±5.2 pmol · h^–1 · (g^–1 protein, respectively; P<0.001). As previously shown, leucine oxidation was found to be increased in the presence of glucose whereas glucose oxidation decreased. In contrast, the presence of glucose strongly diminished valine oxidation (19.2±1.9 vs 63.1±4.7 pmol · h^–1 · (g^–1 protein; P<0.001) whereas glucose oxidation was increased in the presence of valine (268.2±14.9 vs 229.6±16.2 pmol · h^–1 · g^–1 protein; P<0.05). We conclude that in rat MTAL, under near physiological conditions (in the presence of glucose, as in vivo), leucine is a preferential respiratory fuel as compared to valine. However, valine supports energetic salt transport and facilitates glucose oxidation.     

Measurement of hepatic blood flow in the rat using fractional clearance of indocyanine green and colloidal radiogold

Two new methods are described to measure hepatic blood flow in the anaesthetized rat. These methods are based on the fractional clearance and extraction of indocyanine green, which is removed by hepatocytes, and of colloidal radiogold, which is removed by Kupffer cells. Hepatic blood flow was found to be 2.11±0.35 ml·min^–1·g liver^–1 (mean ±SD) and 2.01±0.31 ml·min^–1·g liver^–1, respectively, with these two substances (P>0.80).     

Proximal tubular transport and urinary excretion of sodium after renal denervation in sodium depleted rats

The effect of unilateral renal denervation on renal handling of water, sodium and potassium was studied with clearance and micropuncture techniques in sodium depleted anaesthetized rats in the nondiuretic state. In clearance experiments renal denervation resulted in a +140 and +320% increase in urine flow and potassium excretion, but sodium excretion of innervated (I) and denervated (D) kidneys was similar (I: 12.0±2.0, D: 14.0±3.6 nM·min^–1·g^–1; NS). However, upon the loop diuretic furosemide (1 mg·kg^–1), a marked denervation natriuresis was observed (I: 2.8±0.9, D: 5.9±1.0 M·min^–1;P<0.05) and denervation diuresis and kaliuresis persisted, too (+95 and +60%, respectively). Micropuncture results revealed that fractional reabsorption of filtrate to late proximal puncture site was depressed by renal denervation from 62 to 49% while no change in time control rats was seen (64±2 vs. 64±1%; NS). In micropuncture experiments besides augmented urine flow (+82%) from D kidneys also a small denervation natriuresis was present (I: 21.6±6.4, D: 29.2±7.0 nM·min^–1;P<0.05). It is concluded that the lack or marked attenuation of denervation natriuresis in sodium depleted rats were the result of an almost complete compensatory distal reabsorption of the excess sodium (but not of water and potassium) leaving the proximal tubule after denervation. The distal adaptive response can be overcome by furosemide.     

Effects of parathyroid hormone and N6,O2′-dibutyryl cyclic AMP on Ca2+ transport across the rabbit distal nephron segments perfused in vitro

Effects on Ca²⁺ transport of parathyroid hormone (PTH) and N⁶,O²-dibutyryl adenosine 3,5-cyclic monophosphate (DB-cAMP) were examined in the rabbit distal nephron segments including the cortical thick ascending limb of Henle's loop (CAL), the connecting tubule (CNT) and the cortical collecting tubule (CCT) by the in vitro perfusion technique. When PTH (10^–8 mol·l^–1) was added to the bath, efflux of Ca²⁺ (pmol·mm^–1·min^–1) was increased from 6.29±1.46 to 7.96±1.66 (P<0.02) in the CAL, and from 8.55±1.30 to 13.73±1.24 (P<0.001) in the CNT, respectively, without changes in influx of Ca²⁺. The effect of PTH on Ca²⁺ transport in the CAL, however, was abolished when phosphate concentration in the medium was reduced from 3.0 to 1.0 mmol·l^–1. When DB-cAMP (10^–3 mol·l^–1) was added to the bath, efflux of Ca²⁺ was also increased from 7.01±0.83 to 9.40±0.82, (P<0.05) in the CAL, and from 13.11±0.89 to 19.74±0.52 (P<0.005) in the CNT, respectively. By contrast, neither PTH nor DB-cAMP affected efflux of Ca²⁺ in the CCT. PTH did not affect the transepithelial voltage either in the CAL or in the CNT. But in the CNT, DB-cAMP decreased the voltage from –14.1 to –9.4 mV. The response of adenylate cyclase activity to PTH in the collagenase treated isolated nephron segments was also examined. Significant increases in adenylase cyclase activity were observed in the CAL as well as in the CNT with 10^–6 mol·l^–1 PTH. These data indicate that PTH stimulates Ca²⁺ transport across the CNT probably via activation of the adenylate cyclase-cyclic AMP system. The hormone may also stimulate Ca²⁺ transport across the CAL in a special condition where plasma phosphate concentration is elevated.     

Effects of exercise training on plasma catecholamines and blood pressure in labile hypertensive subjects

Summary Plasma catecholamine concentrations (norepinephrine, NE; epinephrine, E) were measured along with heart rate (HR) and blood pressure (BP) at rest in supine (20 min) and standing (10 min) positions and in response to cycle ergometer exercise (5 min; 60% estimated maximal aerobic power) in 12 hypertensive patients before and after 20 weeks of aerobic training on cycle ergometer (six males, one female) or by jogging (five males). In a control group of labile hypertensive patients (five males, two females), estimated maximal aerobic power as well as HR and BP at rest in the supine and standing positions and in response to exercise were not modified from the first to the second evaluation (43±4 vs 43±5 ml·kg^–1·min^–1). In comparison estimated maximal aerobic power significantly increased in both training groups (cycle: 38±4 to 43±4; jogging: 38±3 to 46±4 ml·kg^–1·min^–1). However HR and BP were not modified following training, except for small reductions in systolic (18.9 to 18 kPa: 142 to 135 mmHg) and diastolic pressures (13.3 to 12 kPa: 100 to 90 mmHg) (p<0.05) at standing rest in the cycle group. Changes in plasma E and NE concentrations at rest and in response to exercise were small and not consistent: plasma NE was lower at standing rest following cycle training, (559±95 vs 462±108 pg·ml^–1) but a similar reduction was observed in the control group (428±45 vs 321±28 pg·ml^–1); plasma E was lower at rest following cycle training (29±7 vs 12±8 pg·ml^–1), but was higher in response to exercise (137±24 vs 419±113 pg·ml^–1). These results are in accordance with previous reports which do not clearly demonstrate that physical training in hypertensive patients lowers BP and the activity or reactivity of the sympathetic system.     

Effects of glucagon on Na+, Cl−, K+, Mg2+ and Ca2+ transports in cortical and medullary thick ascending limbs of mouse kidney

The effects of glucagon on transepithelial Na⁺, Cl^–, K⁺, Ca²⁺ and Mg²⁺ net fluxes were investigated in isolated perfused cortical (cTAL) and medullary (mTAL) thick ascending limbs of Henle's loop of the mouse nephron. Transepithelial ion net fluxes (J _Na ⁺,J _Cl ^–,J _K ⁺,J _Ca ²⁺,J _Mg ²⁺) were determined by electron probe analysis of the collected tubular fluid. Simultaneously the transepithelial voltage (PD_te) and the transepithelial resistance (R _te) were recorded. In cTAL-segments (n=8), glucagon (1.2×10^–8 mol · l^–1) stimulated significantly the reabsorption of Na⁺, Cl^–, Ca²⁺ and Mg²⁺J _Na ⁺ increased from 204±20 to 228±23 pmol · min^–1 · mm^–1,J _Cl ^– from 203±18 to 234±21 pmol · min^–1 · mm^–1,J _Ca ²⁺ from 0.52±0.13 to 1.34±0.30 pmol · min^–1 · mm^–1 andJ _Mg ²⁺ from 0.51±0.08 to 0.84±0.08 pmol · min^–1 · mm^–1.J _K+ remained unchanged: 3.2±1.3 versus 4.0±1.9 pmol · min^–1 · mm^–1. Neither PD_te (16.3±1.5 versus 15.9±1.4 mV) norR _te (22.5±3.0 versus 20.3±2.6 cm²) were changed significantly by glucagon. However, in the post-experimental periods a significant decrease in PD_te and increase inR _te were noted. In mTAL-segments (n=9), Mg²⁺ and Ca²⁺ transports were close to zero and glucagon elicited no significant effect. The reabsorptions of Na⁺ and Cl^–, however, were strongly stimulated:J _Na ⁺ increased from 153±17 to 226±30 pmol · min^–1 · mm^–1 andJ _Cl ^– from 151±23 to 243±30 pmol · min^–1 · mm^–1. The rise in NaCl transport was accompanied by an increase in PD_te from 10.3±1.1 to 12.3±1.2 mV and a decrease inR _te from 19.1±2.7 to 17.8±2.0 cm². No net K⁺ movement was detectable either in the absence or in the presence of glucagon. A micropuncture study carried out in hormone-deprived rats indicated that glucagon stimulates Na⁺, Cl^–, K⁺, Mg²⁺ and Ca²⁺ reabsorptions in the loop of Henle. In conclusion our data demonstrate that glucagon stimulates NaCl reabsorption in the mTAL segment and to a lesser extent in the cTAL segment whereas it stimulates Ca²⁺ and Mg²⁺ reabsorptions only in the cortical part of the thick ascending limb of the mouse nephron. These data are in good agreement with, and extend, those obtained in vivo on the rat with the hormone-deprived model.This study was supported by the Commission des Communautés Européennes, Grant no. ST 23, 00951F (CD) and by Wissenschaftsausschuß der Nato über den DAAD     

Leg muscle blood flow during reactive hyperemia

Summary In normal man at rest transition from the supine to the upright body position is accompanied by autoregulation of the blood flow to tissues in the dependent extremities.In 11 young healthy males the influence of postural changes and external pressure changes on the blood flow in the anterior tibial muscle during reactive hyperemia was studied. The muscle blood flow was evaluated by means of the Xenon-133 wash-out technique. Transmural pressure changes in the resistance vessels were estimated by measuring the systolic blood pressure at ankle level, using the strain-gauge plethysmograph technique. The mean leg muscle blood flow increased from 48 ml·100 g^–1·min^–1 in a body position with the legs elevated 65 cm above heart level, to 101 ml·100 g^–1·min^–1 in the supine position, and to 151 ml·100 g^–1·min^–1 in a sitting position with dependent legs 70 cm below heart level. The muscle blood flows increased from 92 ml·100 g^–1·min^–1 at ambient pressure to 139 ml·100 g^–1·min^–1 at a subatmospheric pressure of –50 mm Hg. The differences were highly significant (P<0.001). Systemic blood pressure measured at heart level did not change during postural changes and external pressure changes. The post-ischemic muscle blood flow was found to increase with the increasing vascular transmural pressure.It is concluded that during reactive hyperemia the normal compensatory vaso-reactions can be inactivated, so that the vessels react passively to changes in transmural pressure.     

Heterogeniety in regulation of glomerular function

The aim was to study differences in filtration driving forces and glomerular filtration rates between superficial and deep nephrons when urine flow rate was altered at the macula densa region. In young rats stop-flow pressures and single nephron glomerular filtration rates (SNGFR) were measured in the superficial proximal tubules and in the loops of Henle in the papilla. SNGFR was also measured with a modified Hanssen technique. The stop-flow pressures of superficial nephrons amounted to 30.9±0.8 mmHg (mean ± SE) and those of juxtamedullary nephrons to 52.2±1.6 mmHg. In the stop-flow condition the net driving filtration forces were calculated to be about 19 mmHg and 50 mmHg for the superficial and deep glomeruli, respectively. In free flow conditions both net driving forces were calculated to be 19 mmHg. The micropuncture technique gave a SNGFR value for superficial nephrons of 29.6±2.9 and for deep nephrons of 84.1±8.5 nl±min^-1 g^-1 kidney weight (KW). With a modified Hanssen technique the corresponding values were 25.8±3.3 and 27.7±2.9 nl. min^-1.g^-1KW. The tubuloglomerular feedback mechanism is considered to have a powerful regulatory influence on the glomerular filtration rate of deep nephrons.     

Respiratory and cardiac responses to exercise — simulating peripheral perfusion in endurance trained and untrained rats

Summary Ventilatory and circulatory drives elicited by exercise-simulating perfusion of the circulatory isolated hindleg were examined in 10 trained (TR) and untrained (UTR) rats. TR were submitted to endurance training on a motordriven treadmill (30·min^–1 at a grade of 10%, 5 days a week for 30 min). Exercise was simulated by perfusion with modified tyrode solutions:I.) hypoxic, enriched with lactic acid (15 mmol·l^–1), II.) normoxic, enriched with lactic acid. III.) hypoxic without lactic acid. Perfusion was performed in anaesthetized animals through cannulae in the femoral artery and vein; the hindled was connected to the rest of the body only by nerve and bone. 10 min of control perfusion (normoxic tyrode solution) was followed by a 20 min test period and another 10 min control perfusion. Apart from heart rate (HR), respiratory rate (RR) and several outflow parameters were measured ([K⁺], [Na⁺], [lactate], pH, PO₂, PCO₂). During control periods HR was slightly higher in UTR than in TR (375.5±3.9 (SE) vs. 364.1±5.5 beats/min^–1,p<0.6 n.s.), and RR in UTR was significantly higher than those in TR (61.5±0.4 bpm vs. 55.5±3.9 breaths·min^–1,p<0.001). During the test periods both HR and RR in UTR increased significantly while in TR they did not (e.g. in series I mean HR and RR in UTR increased by 8.9±1.2 beats·min^–1 and 1.4±0.1 breaths·min^–1 respectively, whereas in TR the changes were-2.9±1.5 beats·min^–1 and -0.8±0.2 breaths·min^–1. A significant difference between UTR and TR can only partly be due to diminished venous [H⁺] caused by better H⁺ buffering in TR. Particularly in the tests with lactic acid, lactate was far above threshold level. It can be concluded that the metabolic stimulus and the afferent branch of the cardiorespiratory reflex have been attenuated by endurance training.Dedicated to J. Stegemann on the occasion of his 60^th anniversary     

Finger and forearm vasodilatatory changes after local cold acclimation

Summary To determine the vascular changes induced by local cold acclimation, post-ischaemia and exercise vasodilatation were studied in the finger and the forearm of five subjects cold-acclimated locally and five non-acclimated subjects. Peak blood flow was measured by venous occlusion plethysmography after 5 min of arterial occlusion (PBF_isc), after 5 min of sustained handgrip at 10% maximal voluntary contraction (PBF_exe), and after 5 min of both treatments simultaneously (PBF_isc+exe). Each test was performed at room temperature (25° C, SE 1 C) (non-cooled condition) and after 5 min of 5'C cold water immersion (cooled condition). After the cold acclimation period, the decrease in skin temperature was more limited in the cold-acclimated compared to the non-acclimated (P<0.01). The PBF_isc was significantly reduced in the cooled condition only in the cold-acclimated subjects (finger: 8.4 ml · 100 ml^–1 · min^–1, SE 1.1,P<0.01; forearm: 5.8 ml · 100 ml^–1 · min^–1, SE 1.5,P<0.01) compared to the non-cooled condition. Forearm PBF_exe was significantly decreased in the cooled condition only in the cold-acclimated subjects (non-cooled: 7.4 ml · 100 ml^–1 · min^–1, SE 1.2; cooled: 3.9 ml · 100 ml^–1 ·min^–1, SE 2.6,P<0.05) indicating that muscle blood flow was also reduced. The application of PBF_isc+exe elicited an increase in peak blood flow only in the forearm of the non-acclimated subjects (non-cooled: 10.4 ml· 100 ml^–1 · min^–1, SE 2.0; cooled: 14.3 ml · 100 ml^–1 · min^–1, SE 2.6,P<0.05) and conversely only in the finger of the cold-acclimated (non-cooled finger: 25.7 ml · 100 ml^–1 · min^–1, SE 4.4; cooled finger: 19.2 ml · 100 ml^–1 · min^–1, SE 3.3,P<0.01). Therefore, subjects cold-acclimated locally showed decreased vasodilatatory responses only when exposed to cold.     

The influence of long-term infusion of the calcium antagonist diltiazem on postischemic acute renal failure in conscious dogs

Summary The influence of long-term infusion of the calcium-entry blocker diltiazem on postischemic acute renal failure was investigated in conscious dogs monitored by implanted instruments. In 18 uninephrectomized beagle dogs on a salt-rich diet, an electromagnetic flow probe and an inflatable plastic cuff were placed around the renal artery. Acute renal failure was induced by inflating the cuff for 180 min in the conscious animal. Group A (n=5, control) received an intraaortic injection of 0.9% NaCl (5 ml/day) from the 3rd day before until the 7th day after ischemia and group B (n=6, posttreatment) an intra-aortic injection of diltizem (5 µg·min^–1·kg^–1) beginning at the end of ischemia until the 7th day. Group C (n=7, pre- and posttreatment) received diltiazem from the 3rd day before until the 7th day after ischemia. In group A, renal blood flow dropped from 149±16 (preischemic) to 129±29 ml·min^–1 on the 1st day after ischemia. In contrast, renal blood flow increased on the 1st postischemic day in both treatment groups by 29±15% (group B,P 0.05) and 14±13% (group C). In the following days, there was no significant difference in renal blood flow between groups A, B and C. In group B, the reduction of the glomerular filtration rate was similar to that in the control group. In group C, the glomerular filtration rate was significantly less reduced than in group A (34±1.8 preischemically to 17±5.4 on day 1,P 0.05 and 20±4.1 ml·min^–1 on day 7,P 0.05). Plasma renin activity increased in both diltiazem groups, more pronounced so in group B (from 3.7±1.0 on day 1 to 16.2±7.9 ng ATI·ml^–1·h^–1 on day 7,P 0.05). In contrast to groups A and B, the increase in fractional sodium excretion was less pronounced in group C. Likewise, the decrease in free water-reabsorption was less marked than in groups A or B. It was apparent that diltiazem, when administered pre- and post-ischemically, preserved glomerular filtration rate and renal blood flow. When diltizem was given solely postischemically there was an improvement in renal blood flow, but no significant influence on glomerular filtration rate. We therefore conclude that mainly tubular factors, in addition to the attenuation of postischemic vasoconstriction, are involved in the protective effect of diltiazem on postischemic acute renal failure in conscious dogs.Abbreviations ARF acute renal failure - C_osmol clearance of osmolarity - E_Na urinary excretion rate of sodium - FE_Na fractional excretion rate of sodium - GFR glomerular filtration rate - HR heart rate - NE norepinephrine - PAM mean arterial blood pressure - PRA plasma renin activity - RBF renal blood flow - RVR renal vascular resistance - T_H2_O free water reabsorption - V_U urine volume     

Arterial diameter during central volume depletion in humans

The luminal diameter of the radial artery was followed by high frequency ultrasound during 50° head-up tilt-induced central volume depletion in ten healthy subjects of whom six were tilted twice and pretreated with the serotonin receptor antagonist methysergide or placebo following a double-blind randomized design. Eight subjects without active treatment experienced presyncopal symptoms after 16–45 (mean 32 min). Central volume depletion was indicated by an increase in mean thoracic electrical impedance [from 31.5 (SEM 1.6) to 33.4 (SEM 1.7) P < 0.05]. Cardiac output decreased [from 4.1 (SEM 0.3) to 2.2 (SEM 0.3) l · min^–1] and heart rate [HR, from 64 (SEM 3) to 100 (SEM 7) beats · min^–1], mean arterial pressure {MAP, from 77 (SEM 4) to 89 (SEM 2) mmHg [10.3 (SEM 0.53 to 11.9 (SEM 0.27) kPa]} and total peripheral resistance {TPR, from 19 (SEM 2) to 34 (SEM 4) mmHg · min · l^–] [2.5 (SEM 0.27) to 4.5 (SEM 0.53) kPa · min^–1]} increased; but with the appearance of presyncopal symptoms, HR, MAP and TPR were reduced to 65 (SEM 8) beats · min^–1, 46 (SEM 4) mmHg [6.1(SEM 0.53) kPa] and 18 (SEM 3) mmHg · min · l^–1 [2.4 (SEM 0.4) kPa · min^–1 · l^–], respectively (P < 0.05). Vascular resistance was reflected in the arterial diameter which decreased from 2.42 (SEM 0.17) to 2.27 (SEM 0.14) mm during head-up tilt and increased to 2.71 (SEM 0.14) mm with the appearance of presyncopal symptoms (P < 0.05). Methysergide reduced the resting radial (15 ± 2%) and temporal artery diameters (10 ± 3%) (P < 0.05); however, it affected neither tilt-tolerance nor the central cardiovascular response to tilt. The results suggested a serotonergic influence on arterial tone at rest, and demonstrated that vessels as large as the radial artery participated in vascular control during central volume depletion independent of such a serotonergic influence.     

Effects of pre-exercise carbohydrate feedings on muscle glycogen use during exercise in well-trained runners

Summary The purpose of this study was to examine the effects of pre-exercise glucose and fructose feedings on muscle glycogen utilization during exercise in six well-trained runners ( =68.2±3.4 ml·kg^–1·min^–1). On three separate occasions, the runners performed a 30 min treadmill run at 70% . Thirty minutes prior to exercise each runner ingested 75 g of glucose (trial G), 75 g of fructose (trial F) or 150 ml of a sweetened placebo (trial C). During exercise, no differences were observed between any of the trials for oxygen uptake, heart rate or perceived exertion. Serum glucose levels were elevated as a result of the glucose feeding (P<0.05) reaching peak levels at 30 min post-feeding (7.90±0.24 mmol·l^–1). With the onset of exercise, glucose levels dropped to a low of 5.89±0.85 mmol·l^–1 at 15 min of exercise in trial G. Serum glucose levels in trials F and C averaged 6.21±0.31 mmol·l^–1 and 5.95±0.23 mmol·l^–1 respectively, and were not significantly different (P<0.05). There were also no differences in serum glucose levels between any of the trials at 15 and 30 min of exercise. Muscle glycogen utilization in the first 15 min of exercise was similar in trial C (18.8±8.3 mmol·kg^–1), trial F (16.3±3.8 mmol·kg^–1) and trial G (17.0±1.8 mmol·kg^–1), and total glycogen use was also similar in trial C (25.6±7.9 mmol·kg^–1), trial F (35.4±5.7 mmol·kg^–1) and trial G (24.6±3.2 mmol·kg^–1). In contrast to previous research, these results suggest that pre-exercise feedings of fructose or glucose do not affect the rate of muscle glycogen utilization during 30 min of treadmill running in trained runners.