bluuebunny/crossref_metadata_2025 huggingface dataset:
The filter properties of the arterial beds of organs in rats
Authors: YOUNG S. T. , WANG W. K. , CHANG L. S. , KUO T. S.
Published: December 2008

The frequency properties of arterial beds in organs were studied by temporarily ligating the renal, the gastric, the splenic or the superior mesenteric arteries of rats. Blood‐pressure waves of the tail arteries were recorded before and during the ligations, and were analysed by Fourier's transformation. Their frequency spectra have been found to change profiles following specific patterns with the ligations of different arteries. The results were significant with regard to the frequency selectivities of the organic arterial beds. Such frequency properties can be clearly explained when the circulation system is viewed as an electrical circuit network in which the organic arterial beds work as filters.
The effect of training on the recovery from immobilization‐induced bone loss in rats
Authors: TUUKKANEN J. , PENG Z. , VÄÄNÄNEN H. K.
Published: December 2008

We studied the effect of exercise on the recovery from osteoporosis induced by immobilization in growing laboratory rats. The right hind limb of male rats was immobilized by cast for 2 weeks. The rats were then divided into control and exercise groups. The controls were allowed to move freely in their cages and the exercise group was running for 1 hour every day. After 2 weeks immobilization, the ash weight of the immobilized tibia decreased to 85.2±0.6% (P < 0.001) from that of contralateral tibia. After removal of the cast, the bone mass recovered and, in 9 weeks, the decrease of ash weight was reduced to 2.9 ± 0.8% and 4.2±0.3% in the control and exercise groups, respectively. There was no statistical difference in ash weights between the running and control groups and the trabecular bone volume in the distal femur was also equal in both groups. Immobilization reduced the incorporation of [45Ca] into the tibia. After remobilization, the [45Ca]‐incorporation was found to be significantly higher in the recovering leg than in the control leg. Exercise further stimulated [45Ca]‐incorporation into the recovering tibia.
Bio‐energetic changes in human gastrocnemius muscle 1–2 days after strenuous exercise
Authors: KEMP G. J. , TAYLOR D. J. , RADDA G. K. , RAJAGOPALAN B.
Published: December 2008

[31P]magnetic resonance spectroscopy was used to study the metabolic sequelae of intense muscular activity in gastrocnemius of seven subjects 1–2 days after a 67‐mile bicycle ride. The muscle was examined at rest, during a test exercise and during recovery from test exercise. Post‐ride and pre‐ride results were compared. At rest, the ratio of phosphocreatine to ATP (PCr/ATP) was increased post‐ride; during test exercise PCr/(PCr + Pi) was lower post‐ride; and the recoveries of PCr, Pi and PCr/(PCr + Pi) after test exercise were delayed, with decreased ‘overshoot’ of PCr/(PCr + Pi) (which is due to recovery of Pi to below its resting value). Mild mitochondrial damage (perhaps due to exposure to high cytosolic [Pi] during the bicycle ride) may explain some of these results. In contrast to reports of largely eccentric exercise there was no increase in resting Pi/ATP. We have thus demonstrated perturbations of muscle bio‐energetics 1–2 days after strenuous exercise, in the absence of convincing enzymological evidence of muscle damage.
Effects of Amrinone on shortening velocity, force development and ATPase activity of demembranated preparations of rat ventricular myocardium
Authors: MÖRNER S. E. J. N. , CANEPARI M. , BOTTINELLI R. , CAPPELLI V. , REGGIANI C.
Published: December 2008

This study analyses the effects of Amrinone (bipyridine derivative with phosphodiesterase inhibitor properties) on the myofibrillar apparatus of rat myocardium.

Thin trabeculae were isolated from the right ventricle and chemically demembranated. Force development and shortening velocity were measured during maximal calcium activations (pCa = 4.45) in control conditions and in the presence of 1–3 mM Amrinone. Maximum shortening velocity was obtained both from extrapolation of the force‐velocity curve and with the slack test method. Amrinone was found to significantly reduce maximum shortening velocity and force development.

Myofibrils and myosin were prepared from rat ventricular myocardium and their ATPase activity was assessed in control conditions and in the presence of Amrinone (0.3–6 mM). Ca–Mg dependent myofibrillar ATPase activity which was determined at low ionic strength was depressed by Amrinone in a dose‐dependent way. Ca‐stimulated ATPase activity determined at high ionic strength in myofibril or myosin preparations was not affected. Furthermore, Amrinone did not influence the pCa‐ATPase activity curve of the myofibrillar preparations. A comparison between the inhibitory effects of Amrinone on myofibrils prepared from euthyroid rats and myofibrils prepared from hypothyroid rats was carried out. The ATPase activity was significantly less depressed in myofibrils prepared from hypothyroid rats than in those prepared from euthyroid rats.

These results provide the first evidence of an effect of Amrinone on ATP splitting and force generation in the myofilament system of cardiac muscle.
ESR‐measurement of production of oxygen radicals in vivo before and after renal ischaemia in the rabbit
Authors: HARALDSSON G. , NILSSON U. , BRATELL S. , PETTERSSON S. , SCHERSTÉN T. , ÅKERLUND S. , JONSSON O.
Published: December 2008

This study describes a spin trap technique to determine production of oxygen radicals in rabbit kidneys after ischaemia and reperfusion. OXANOH was infused intraarterially. When exposed to oxygen free radicals OXANOH is oxidized to the stable radical OXANO. The concentration of OXANO in samples of renal venous blood was determined by ESR. Production of oxygen radicals was calculated from the amount of OXANO in the venous blood and the blood flow which was determined by an ultrasound technique. The radical production at reperfusion after ischaemia was expressed as a per cent of the pre‐ischaemic value. A drastic increase in radical production was observed during (60 min) reperfusion after 60 min of ischaemia. Pretreatment with oxypurinol (20 mg kg‐1) before ischaemia and before recirculation almost completely abolished the rise in radical production at recirculation. Similar results were obtained when oxypurinol was given before recirculation only.
Adrenergic and non‐adrenergic cardiovascular effects of thyrotropin‐releasing hormone (TRH) in the anaesthetized rabbit
Authors: SELIGSOHN E. E.
Published: December 2008

The effects of thyrotropin‐releasing hormone (TRH) on regional blood flows were studied in urethane‐anaesthetized rabbits. Experiments were performed both with and without adrenergic antagonist pretreatment. The tracer microsphere method was used to measure blood flow. TRH (0.1 mg kg‐1) caused an increase in mean arterial blood pressure (MAP) from 9.8 ± 1 to 11.8 ± 0.8; a higher dose (1 mg kg‐1) increased the blood pressure to 15.2±1 kPa (P < 0.001). Total cerebral blood flow (CBFtot) increased to 137 ± 10% (P< 0.05) of control at the lower dose and to 214±16% (P< 0.001), at the higher dose. A reduction in blood flow at both doses of TRH in several peripheral organs indicates that the pressor effect was mainly due to an effect on the peripheral vascular resistance. In prazosin‐pretreated animals in which the MAP was normalized by ligation of the thoracic aorta, TRH elicited an increase in the CBFtotto 131 ± 12% (P< 0.05) of control. In the iris, TRH caused vasodilation in prazosin‐pretreated animals. In experiments with combined α‐ and β‐adrenergic blockade, a non‐adrenergic vasoconstricting effect of TRH was seen in some peripheral organs.

The results indicate that TRH activates the sympathetic nervous system thus causing an increased vascular resistance and MAP; these effects are mediated mainly by an α1‐adrenergic mechanism. In the spleen, the gastric mucosa and the adrenal glands, the vasoconstriction caused by TRH was partly non‐adrenergic. The vasodilation seen in the small intestine and the anterior uvea after TRH treatment and adrenoceptor blockade may be explained by effects on the parasympathetic nervous system. The vasodilating effect of TRH in the brain does not seem to involve α‐ or β‐adrenergic mechanisms.
Different ion channel mechanisms between low concentrations of capsaicin and high concentrations of capsaicin and nicotine regarding peptide release from pulmonary afferents
Authors: LOU Y.‐P. , FRANCO‐CERECEDA A. , LUNDBERG J. M.
Published: December 2008

Vagal nerve stimulation (1 Hz for 1 min), capsaicin (10‐8M and 10‐6M), resiniferatoxin (3 × 10‐10M) and nicotine (10‐4M) evoked a non‐cholinergic bronchoconstriction in the isolated perfused guinea‐pig lung preparation. Simultaneously there was an increase in the perfusate levels of calcitonin gene‐related peptide‐like immunoreactivity, suggesting release from sensory nerves. Both the bronchoconstriction and peptide release evoked by a low concentration of capsaicin (10‐8M) and that evoked by nerve stimulation were depressed by tetrodotoxin, suggesting involvement of Na+channel dependent depolarization. Since the effects of capsaicin (10‐8M) and vagal nerve stimulation were inhibited by ω‐conotoxin but not influenced by nifedipine, the Ca2+‐channel involved is probably of N‐type. Furthermore, the capsaicin analogue resiniferatoxin also evoked ω‐conotoxin sensitive peptide release and bronchoconstriction. At the higher capsaicin concentration (10‐6M), the functional response was only slightly inhibited by wconotoxin or tetrodotoxin indicating that capsaicin at this concentration evoked peptide release and functional effects through other mechanisms, probably involving Ca2+fluxes in the non‐selective cation channel associated with the proposed capsaicin receptor. The nicotine (10‐4M) evoked peptide release and bronchoconstriction were only marginally influenced by ω‐conotoxin or tetrodotoxin.

It is concluded that the ion‐channel mechanisms underlying the peptide releasing properties of antidromic nerve stimulation and low concentrations of capsaicin are similar and depend on action potential propagation, whereas capsaicin in high, toxic concentration and nicotine mainly act via receptor operated channels.
Metabolic rates of minke whales (Balaenoptera acutorostrata) in cold water
Authors: FOLKOW L. P. , BLIX A. S.
Published: December 2008

Body temperature, blubber thickness and lung capacity (Ve) were recorded in newly killed minke whales, while respiratory frequency (f) was determined in free‐swimming animals. Mean deep (thoracic) body temperature was 34.7±0.8 (SD) °C (n= 14). Weighted mean core/blubber interface temperature in animals caught in 2.5‐5.5 °C water was 28.8±1.7 °C (n= 8). The minimum average rate of sensible heat loss (HLs) was 3.81±0.53 (SD) W kgw‐0.75 (n= 8) in animals with body masses (w) in the range of 1840 to 5740 kg, HLs being inversely proportional to ω (HLS= ‐ 2.98 10‐4 w + 4.89 W kgω‐0 75 (n= 8, r‐2= 0.73, P < 0.01)). The average rate of respiratory heat loss (HLr) was 0.26±0.04 (SD) W kgw‐0.75, regardless of w, in the same 8 animals. Total rates of heat loss (HL=HLr+HLs) in 2.5‐5.5 °C water ranged between 3.40 and 4.87 W kgw‐0.75, with an average of 4.06±0.52 (SD) W kgw‐0.75 (n= 8). Estimates of oxygen consumption based on records of f and Vc and data on oxygen extraction from other cetaceans, yielded a range of metabolic rates which compared nicely with the calculated HL values.
Power spectral analysis of heart rate and blood pressure variability in anaesthetized dogs
Authors: HEDMAN A. E. , HARTIKAINEN J. E. K. , TAHVANAINEN K. U. O. , HAKUMÄKI M. O. K.
Published: December 2008

Short‐term oscillation of heart rate and blood pressure are mainly regulated by the automatic nervous system. It has been proposed that non‐neural factors, such as changes in intrathoracic pressure, can strongly modulate this rhythmicity. Our aim was to evaluate the effect of changing intrathoracic pressure and central autonomic nervous activity on heart rate and blood pressure variability. Evaluation was performed by using spectral analysis techniques with autoregressive modelling. The variability in heart rate and blood pressure remained in animals with open chest or paralysed respiratory muscles. After vagotomy, the variability in heart rate decreased, but not that of blood pressure. Total spinal anaesthesia elicited a decrease in the variability in blood pressure. The pharmacological blockade of α‐ and β‐receptors further decreased both variabilities. It was concluded that in anaesthetized dogs heart rate and blood pressure variability are mainly of central origin and non‐neural factors have only minor effect on these central rhythms. High (> 0.15 Hz), medium (0.07–0.15 Hz) and, obviously low (0.00–0.07 Hz) frequency variations in heart rate are mostly mediated vagally. In blood pressure, medium and obviously low frequency variations are modulated by sympathetic nervous system, whereas high frequency variations are secondary to the heart rate variation.
Lipid peroxidation capacities in the myocardium of endurance‐trained rats and mice in vitro
Authors: KIHLSTRÖM M. T.
Published: December 2008

The endurance‐training programme in Experiment 1 (Exp. 1) consisted of a total swimming time of 149–159 h per male Han Wistar rat and in Experiment 2 (Exp. 2) the male NMRI‐mice run on a treadmill at a speed of 25 m min‐1 1 h per day, 5 days a week for 3 weeks. One group of the rat hearts was perfused with 0.3 mm cumene hydroperoxide (CumOOH) while the others were fractioned (mitochondria, sarcolemma and sarcoplasmic reticulum) and these cell fractions and homogenates were used to determine the total concentration of peroxidative lipids and the susceptibility to lipid peroxidation. The perfusion with CumOOH caused the release of thiobarbituric acid reactive substances (TBARS) into the perfusate. The release of TBARS from the trained hearts was smaller than that of the control hearts (P < 0.01). The concentration of TBARS was also smaller in the myocardium of the right ventricle of the trained rats (P < 0.01). The concentration of reduced GSH remained at a higher level after the CumOOH perfusion suggesting a better redox state in the hearts of trained animals. The concentration of the lipids susceptible to lipid peroxidation was lower in the homogenates of the trained rat hearts (P < 0.05). However, this decrease could not be explained by any of the tissue fractions used when studied in rat hearts. In Exp. 2 the total concentration of lipids susceptible to peroxidation remained unchanged in the mice hearts. However, endurance training by running decreased (P < 0.01) the lipid peroxidation rate in mouse hearts and also decreased (P < 0.05) the sensitivity of myocardium to in vitro stimulated lipid peroxidation. The results suggest that endurance training by swimming or by running reduces the susceptibility of myocardium of rats and mice to chemically induced lipid peroxidation injuries in vitro.
Vasoconstrictor reactions in spontaneously hypertensive rats versus Wistar Kyoto can be increased or decreased depending on the conditions of perfusion
Authors: RODIONOV I. M. , TARASOVA O. S. , VAKULINA T. P. , KOSHELEV V. B. , PINELIS V. G. , MARKOV Ch. M.
Published: December 2008

The reactions of resistance vessels in SHR and WKY hindquarters were compared during saline or blood perfusion. During saline constant‐flow perfusion at all initial pressures (80–200 mmHg) sympathetic vasoconstrictor effects were greater in SHR than those in WKY. During perfusion at constant and equal pressure vasoconstrictor responses were greater in SHR vs. WKY only at high pressure ‐ 200 mmHg. On the other hand, under constant pressure conditions at lower pressures (80 and 120 mmHg) sympathetic stimulation induced weaker responses in SHR than in WKY, which at, for example, 80 mmHg was the case at every frequency of sympathetic stimulation used (2–20 Hz). Also, the responses to exogenous noradrenaline and vasopressin occurred during perfusion at low (80 mmHg) and for both equal constant‐pressure conditions lower in SHR than in WKY. Comparison of sympathetic effects in SHR and WKY during blood hindquarter perfusion revealed similar results. Also, when SHR and WKY responses were compared at their ordinary levels of constant‐pressure, sympathetic vasoconstrictor effects in SHR were lower than those in WKY.
In vivoandin vitrostudies on effects of β‐endorphin and naloxone on sex steroids in the water frog,Rana esculenta
Authors: ZERANI M. , GOBBETTI A.
Published: December 2008

The effects of β‐endorphin and its receptor antagonist, naloxone, on progesterone, androgens, and oestradiol‐17β release in male and femaleRana esculentawere studiedin vivoandin vitro. In thein vivoexperiments the frogs underwent hypophysectomy, gonadectomy or both, or were left intact; the animals were injected with β‐endorphin or naloxone and killed after 15, 30, 90 and 240 min. In thein vitroexperiments inter‐renal, testis and ovary, all with and without added pituitary, were incubated with β‐endorphin or naloxone for 10, 20, 40 and 80 min. Thein vivoandin vitrodata from males and females were in agreement. In vivo β‐endorphin increased progesterone in all experimental groups and oestradiol in intact and hypophysectomized frogs, while it decreased androgens in all experimental groups. In vitro β‐endorphin increased progesterone in inter‐renal and gonadal tissue, and oestradiol in gonads only, while it decreased androgens in inter‐renals and gonads. In vivo andin vitronaloxone induced opposite effects to β‐endorphin.

These data suggest that inRana esculenta, opioids are involved in the modulation of hypothalamo‐pituitary‐inter‐renal and gonadal axes. In particular, the data indicate a direct effect of opioids on inter‐renal and gonadal sex steroid production.
Mechanisms in man for rapid refill of the circulatory system in hypovolaemia
Authors: LÄNNE T. , LUNDVALL J.
Published: December 2008

Compensatory, net fluid transfer across the capillaries was studied in the arm of man with plethysmographic technique during experimental hypovolaemia induced by lower body negative pressure (LBNP). Thirty, 60, and 110 cmH2O LBNP evoked rapid transfer of fluid from tissue to blood at average rates of 0.053, 0.088 and 0.147 ml min‐1 100 ml‐1 soft tissue, i.e. graded responses typical for a true homeostatic regulation. Other experiments demonstrated a net fluid absorption not only from the arm but also from a wide range of skeletal muscle and skin regions in the body during experimental hypovolaemia, i.e. the more or less generalized response required if the absorption process is to contribute importantly to plasma volume regulation. In a third series of experiments it was shown that gradually applied LBNP was a much less efficient stimulus for fluid gain into the circulation than rapidly instituted LBNP, tentatively explaining the fairly slow plasma volume refill in man in previous literature after experimental, true and necessarily slow blood loss. Taken together, the findings described warrant the conclusion that the described process of fluid gain into the circulation may be a very important component in the overall homeostatic circulatory regulation in states of hypovolaemia. The data in fact suggest that the process might be capable of increasing plasma volume by as much as 600 ml within only 10 min, suggesting that such plasma volume control might be much more potent than previously believed.
Post‐prandial cardiovascular responses in man after ingestion of carbohydrate, protein or fat
Authors: WAALER B. A. , ERIKSEN M.
Published: December 2008

Changes in cardiac output and in superior mesenteric arterial flow were followed with Doppler ultrasound techniques in five young, healthy persons for 2 h after ingestion of medium‐sized (4 MJ), fluid meals containing either carbohydrate, protein, fat or water only. Measurements were carried out before meals and at regular post‐meal intervals, during which mean arterial blood pressure was also followed.

All energy‐containing meals caused marked and gradually developing post‐prandial increases in cardiac output as well as in superior mesenteric arterial flow. The maximum flow levels were reached in the course of 30–60 min and maintained until the observations ended after 2 h. The intake of water caused no such flow increases.

There were considerable interpersonal variations in the size and in the speed of development of the flow increases after the three types of energy‐containing meals. The flow‐increasing effects of the three meal types were not significantly different, even if the most marked increases (median values about 1 1 min‐1 for both cardiac output and superior mesenteric arterial flow) occurred after carbohydrate meals.

The marked effects on circulation of the three food components were also revealed in the calculated, integrated amounts of ‘extra’ cardiac output and superior mesenteric arterial flow observed in the course of the 2 h following the meal. Values of more than 100 1 for such ‘extra’ flows were seen after carbohydrate meals.

The marked ingestion‐released increase in blood flow to the splanchnic organs is apparently partly met by an increase in cardiac output, and partly by some redistribution of flow, which benefits the digestive system.
Short‐term restraint stress and s.c. saline injection alter the tissue levels of substance P and cholecystokinin in the peri‐aqueductal grey and limbic regions of rat brain
Authors: ROSÉN A. , BRODIN K. , ENEROTH P. , BRODIN E.
Published: December 2008

Rats were exposed to short‐term restraint (held by the tail for 1 min), injected s.c. with saline or subjected to the combination of these treatments. Fifteen and 30 min after these treatments the means serum corticosterone level was significantly increased by more than four times, compared to rats taken directly from their home cages, indicating a stress response. In the peri‐aqueductal grey, the level of substance P‐like immunoreactivity was increased by 45% (P < 0.01) and 65% (P < 0.01) 30 and 60 min after the combined treatment, respectively. Significant increases of the level of substance P‐like immunoreactivity in the peri‐aqueductal grey were also found after restraint only and after a s.c. saline injection. Similar, but less marked, changes in the level of cholecystokinin‐like immunoreactivity in the PAG were also seen. In the accumbens a significantly decreased level of substance P‐like immunoreactivity was encountered at 15 and 30 min after treatment, while the levels of cholecystokinin‐ and neuropeptide Y‐like immunoreactivity were not significantly changed. In other regions studied, no effects on peptide levels were seen. The changes in peptide levels had a time course similar to that of the increase in serum corticosterone. Also the successive removal of rats from a common cage was found to increase significantly the serum corticosterone and the substance P‐like immunoreactivity in the peri‐aqueductal grey in the animals that were taken late in sequence from the cage. The present results demonstrate that apparently innocuous treatment may induce rapid and marked changes of brain peptide levels, the changes being different depending on the peptide and region investigated. Further on, the effects encountered are similar in magnitude to those previoush demonstrated after various drug treatments.
Vagally mediated release of gastrin and cholecystokinin following sensory stimulation
Authors: UVNÄS‐MOBERG K. , LUNDEBERG T. , BRUZELIUS G. , ALSTER P.
Published: December 2008

The aim of the present study was to investigate whether gastrin, cholecystokinin (CCK) and somatostatin secretion can be influenced by sensory stimulation and if so, whether such effects are mediated via the vagal nerves. Male rats anaesthetized with chloral hydrate were exposed to three different stimuli, i.e. to low frequency (2 Hz) electrical stimulation of muscles via needles (electro‐acupuncture), to thermal stimulation at 40 °C or to vibration at 100 Hz. The two former stimuli activate mainly small and medium sized myelinated fibres from muscles and skin respectively, whereas vibration activates large myelinated fibres from skin, subcutaneous tissue and muscles. Experiments were also performed on animals that were vagotomized or exposed to prior treatment with atropine (0.5 mg kg‐1). Blood was collected at various time intervals and plasma levels of gastrin, CCK and somatostatin were measured with radioimmunoassay (RIA).

All three stimuli, i.e. electro‐acupuncture, vibration and thermal stimulation caused significant elevations of gastrin (103 ± 11–151 ± 16 pm, 105 ± 8–140 ± 12 pm and 105 ± 14–162 ± 4 pm) and cholecystokinin (9 ± 0.8–15 ± 2.8 pm, 8 ± 0.5–10 ± 1.5 pm and 8.0 ± 0.5–10.5 ± 1.5). Somatostatin was raised in response to electro‐acupuncture (10 ± 1–14 ± 3 pm). Vagotomy and atropinization abolished the release of gastrin and CCK in response to all three stimuli. CCK levels were significantly reduced following electro‐acupuncture in atropinized rats. In conclusion, gastrin and cholecystokinin release is stimulated by activation of sensory afferent, originating in skin, subcutaneous tissue as well as in muscle. Some of these effects are vagally mediated.
Secretin stimulates bile ductules to secrete both H+ and HCO‐3‐ions
Authors: VILLANGER O. , VEEL T. , HOLTHE M. R. , Jr E. J. CRAGOE , RÆEDER M. G.
Published: December 2008

Secretin‐dependent ductular HCO‐3 secretion into bile may involve secretion of H+ to interstitial fluid and HCO‐3 to bile by the ductular epithelium. To determine whether secretin causes bile ductules to secrete H+, we have examined the effect of secretin on the elimination of an intracellular acid load from bile ductular epithelium during pharmacological blockade of Na+‐H+ exchange and in the absence of HCO‐3. Microdissected bile ductules from pigs were suspended in HCO‐3 free HEPES buffer and loaded with acid using an NH4Cl prepulse technique. Intracellular pH was measured using dual‐wavelength excitation of BCECF fluorescence. Na+‐H+ exchange was defined as a Na+‐dependent and amiloride‐ and 5‐(N,N‐hexamethylene)‐amiloridesensitive efflux of H+‐ions following acid loading. We found that secretin stimulated ductular H+ secretion independent of Na+‐H+ exchange. Blockade of Na+‐H+ exchange by hexamethylene‐amiloride did not affect secretin‐dependent ductular HCO‐3 choleresis in vivo. We conclude that secretin stimulates bile ductules to secrete H+‐ions to interstitial fluid as well as HCO‐3 ions to bile by a mechanism independent of Na+‐H+ exchange.
Renal interstitial pressure and tubuloglomerular feedback control in rats during infusion of atrial natriuretic peptide (ANP)
Authors: MORSING P. , STENBERG A. , CASELLAS D. , MIMRAN A. , MÜLLER‐SUUR C. , THORUP C. , HOLM L. , PERSSON A. E. G.
Published: December 2008

Atrial natriuretic peptide (ANP), injected at physiological concentrations, is known to induce both natriuresis and diuresis. It has been suggested by some investigators that these changes result from an increasing glomerular filtration rate (GFR), but others have been unable to demonstrate an increased GFR. The tubuloglomerular feedback (TGF) mechanism is an important regulator of GFR, and the sensitivity of TGF is decreased during ANP administration. Furthermore, resetting of TGF is, in most instances, related to changes in renal interstitial hydrostatic and oncotic pressures. It is also known that ANP may increase capillary permeability which may change renal interstitial pressure.

The present study was performed to examine renal interstitial pressures and the TGF mechanism during ANP infusion. In accordance with previous studies, TGF sensitivity was found to be decreased. The tubular flow rate which elicited half the maximal drop in stop‐flow pressure (Psf) was increased from 18.5 to 25.7 nl min‐1. In contrast, ANP infusion resulted in a decreased interstitial hydrostatic pressure and an increased interstitial oncotic pressure. From previous experiments, such changes in interstitial pressures would be expected to increase TGF sensitivity. The changes in interstitial pressure cannot, therefore, directly explain the resetting of the feedback mechanism.

In conclusion, the present paper shows a decreased renal net interstial pressure after intravenous administration of ANP.
Brain interstitial volume fraction and tortuosity in anoxia. Evaluation of the ion‐selective micro‐electrode method
Authors: LUNDBÆK J. A. , HANSEN A. J.
Published: December 2008

The micro‐electrode method for determination of interstitial volume fraction (α) (Nicholson & Phillips 1981), was evaluated. The extracellular marker, tetramethylammonium+, is iontophoretically ejected from a micropipette and the change in concentration measured at a distance by an ion‐sensitive micro‐electrode and fitted to a diffusion equation. We used suspensions of human red blood cells as a model system and found that the values of α determined by this method and by haematocrit measurement were linearly correlated (r= 0.94) and not significantly different. The micro‐electrode method was used to characterize the interstitial space in rat brain cortex during normal conditions and during arrest of blood flow supply. Transport of solutes in interstitial space is governed by two characteristics, the interstitial volume fraction and the tortuosity factor. During control conditions, the interstitial volume fraction was 0.18±0.02 (mean±SEM), whereas it decreased to 0.07±0.01 in ischaemia. The tortuosity factor was 1.40±0.05 in controls and increased to 1.63±0.09 during ischaemia. Our measurements support the validity of the micro‐electrode method (Nicholson & Phillips 1981) and demonstrate that arrest of blood supply changes interstitial diffusional characteristics of brain cortex mainly by diminishing the size of the interstitial diffusional space.
Modulation of G proteins and second messenger responsiveness by steroid hormones in GH3rat pituitary tumour cells
Authors: PAULSSEN R. H. , PAULSSEN E. J. , GAUTVIK K. M. , GORDELADZE J. O.
Published: December 2008

We have investigated the modulation of different G proteinα‐ andβ‐subunit levels in prolactin (PRL) and growth hormone producing rat pituitary adenoma cells (GH3cells) in culture after prolonged exposure (6–48 h) to the steroid hormones 17β‐oestradiol and dexamethasone. Gi‐3α‐ and Gβ‐subunits were the only G protein subunits which increased in response to 10‐6m oestradiol (to approximately 150 and 200% of controls, respectively), while the otherα‐subunits investigated (Gsα, Gi‐2αand Goα) remained relatively unchanged. Thyroliberin (TRH)‐and guanosine 5′‐[βγ‐imido]trisphosphate (Gpp(NH)p)‐elicited adenylyl cyclase (AC) activities were reduced during 6–12 h of oestradiol treatment (by 60 and 20%, respectively), while the inhibitory effect of somatostatin (SRIF) increased by approximately 100%. Dexamethasone (10‐6m) increased levels of the stimulatory G protein Gsα(to approximately 340%) and decreased levels of Gi‐3α(to 25%). After 48 h, the AC response to TRH was reduced by approximately 70%, whereas the effect of the other modulators remained close to controls. We conclude that G protein subunits in GH3cells are subject to specific regulation by steroid hormones and that this may be important in the tuning of the responsiveness of PRL secretion to hormones in thein vivosituation.
The ionic mechanism of phenylephrine‐induced rhythmic contractions in rabbit mesenteric arteries treated with ryanodine
Authors: OMOTE M. , KAJIMOTO N. , MIZUSAWA H.
Published: December 2008

Phenylephrine induces endothelium‐independent rhythmic contractions in ryanodinetreated rabbit mesenteric arteries. To elucidate the ionic mechanism of this rhythmic behaviour, rabbit mesenteric arterial rings were suspended in an organ chamber for isometric tension studies. Yohimbine, propranolol, and atropine had no effect on these contractions, minimizing the possibility that transmitter release from nerve terminals was involved. Additionally, the oscillatory contractions were not altered by diphenhydramine, cimetidine, and indomethacin, thus ruling out the involvement of histamine and prostaglandins. This oscillatory response was completely abolished after the removal of extracellular Ca 2+, as well as after Ca 2+ channel blockade by diltiazem or nifedipine. Sparteine and quinidine, Ca 2+‐activated K+ channel antagonists, also abolished the oscillation. In contrast, tetraethylammonium and 3,4‐diaminopyridine, voltage‐dependent K+ channel antagonists, augmented the response. Glibenclamide, an antagonist of the ATP‐sensitive K+ channel, had no effect on the rhythmic contractions. These results suggest that the rhythmic contractions observed in rabbit mesenteric arteries after ryanodine treatment were caused by the movement of Ca 2+ and K+ across the plasmalemma via the voltage‐dependent Ca 2+ channel and the Ca 2+‐activated K+ channel, respectively.
Capillary diffusion capacity for Cr‐EDTA and cyanocobalamine in spontaneously beating rat hearts
Authors: WÅHLANDER H. , FRIBERG P. , HARALDSSON B.
Published: December 2008

In order to obtain a functional estimate of the diffusional capacity of the myocardial capillary bed, the permeability surface area product (PS) for Cr‐EDTA (mol. wt = 341) and cyanocobalamine (vitamin B12, mol. wt = 135) was determined in spontaneously beating Langendorff‐perfused rat hearts over a wide range of coronary flow rates (700–3000 ml min‐1100 g‐l). PS was determined by a single injection, colorimetric indicator dilution technique, allowing multiple, rapid and accurate determinations to be made in the same heart. During maximal vasodilation with nitroprusside Na PS averaged 535 ± 33 and 220 ± 22 ml min‐1100 g‐1for Cr‐EDTA and vitamin B12respectively at the highest flow (2917 ±74 ml min‐1100 g‐1). The vasculature of the heart was found to be highly hererogeneous, since PS increased with flow and there were marked variations of extraction over transit times. A functional estimate of ‘equivalent pore radius’ was obtained from the ratio PSCr.EDTA/PSB12, which was 2.61 ± 0.15 demonstratiag a marked restriction to diffusion corresponding to a pore radius of 51 (41–75) Å. This value is similar to that from skeletal muscle determined by the same method while PS‐values are 40–45 times higher in the heart (Haraldsson & Rippe 1986). Taken together with morphological estimations of capillary surface area and endothelial path depth, these data indicate a 3‐fold increase in the density of pores available for diffusion in the myocardium, compared to skeletal muscle.
Changes in myocardial capillary diffusion capacity during infusion of vasoactive drugs
Authors: WÅHLANDER H. , FRIBERG P. , HARALDSSON B.
Published: December 2008

The present study investigated how variations in coronary vascular resistance and metabolic demand affected myocardial capillary diffusion capacity. Hearts from Wistar rats were perfused with Krebs‐Henseleit‐albumin buffer in a Langendorff preparation, where heart rate (HR), contractility (dP/dtmax) and myocardial oxygen consumption (MVO2) were recorded continuously. Myocardial capillary diffusion capacity was measured as the permeability surface area product (PS) for Cr‐EDTA and vitamin B12by the single injection colorimetric indicator dilution method. After base‐line recordings without drugs, angiotensin II + arginine‐vasopressin was infused, which increased coronary vascular resistance by 90%, stimulated HR by 11%, decreased dP/dtmaxby 21% and reduced MVO2by 4%. PSCr‐EDTAand PSB12, decreased by 24 and 27%, respectively, leaving the ratio PSCr‐EDTA/PSB12unchanged indicating unaltered capillary permeability. Moreover, the reductions in MVO2and PS correlated significantly. During vasodilation: (1) nitroprusside‐NA stimulated HR by 7% and decreased dP/dtmaxby 14%; (2) adenosine reduced dP/dtmaxby 37% and decreased MVO2by 9%; and (3) isoproterenol increased HR, dP/dtmaxand MVO2by 53, 76 and 9%, respectively. However, all three vasodilators reduced PSCr‐EDTAand PSB12in parallel by 7–25% leaving PSCr‐EDTA/PSB12unchanged.

Thus, maximal estimated diffusion capacities were obtained during spontaneous coronary vascular tone, most likely reflecting maximal capillary recruitment in the Krebs‐Henseleit‐albumin perfused heart. The derecruiting effects of the vasoconstrictors were partly overridden by metabolic factors, while the reductions of PS after vasodilation more likely were due to increased heterogeneity in coronary flow.
Modification of regional myocardial performance caused by blood withdrawal and infusion in acute ischaemic canine heart
Authors: ISHIKAWA K. , SHIRATO K. , SAKUMA M. , KANAZAWA M. , MUNAKATA K. , TAKISHIMA T.
Published: December 2008

The effect of changes in preload on regional myocardial motion in acute ischaemia was examined by miniature ultrasonic gauges after left anterior descending coronary artery occlusion in eight open chest dogs with the pericardium preserved. Left ventricular end‐diastolic pressure was varied by blood withdrawal and infusion. When preload changed, isovolumetric shortening in the non‐ischaemic region was inversely related to that in the ischaemic region. When preload decreased, stroke volume decreased and was accompanied by a decrease in end‐diastolic length and ejection shortening in the non‐ischaemic region together with an increase in isovolumetric bulging in the ischaemic region. When preload increased, these variables changed in opposite directions. These results indicate that in acute ischaemia: (1) changes in isovolumetric shortening in the non‐ischaemic and ischaemic regions were related with each other when the level of volume expansion varied, and suggest that; (2) stroke volume is affected by end‐diastolic length, ejection shortening in the non‐ischaemic region and isovolumetric bulging in the ischemic region.
The effect of iron deficiency on skeletal muscle metabolism of the rat
Authors: THOMPSON C. H. , GREEN Y. S. , LEDINGHAM J. G. , RADDA G. K. , RAJAGOPALAN B.
Published: December 2008

Using 31P magnetic resonance spectroscopy we compared skeletal muscle bioenergetics in Wistar rats made chronically anaemic by being fed a diet deficient in iron for 6 weeks with chronically iron deficient animals given a normal diet as well as 5 mg iron dextran at 2 or 7 days before experimentation. Spectra of the gastrocnemius muscle were taken at rest and during stimulation of the sciatic nerve at 2 Hz for 10 min. Relative concentrations of intracellular phosphate (Pi), phosphocreatine (PCr) and ATP were determined. Iron deficiency increased PCr breakdown and production of acid in stimulated skeletal muscle. Recovery of PCr and Pi concentrations after exercise was slow. These metabolic changes are consistent with either a reduction in supply of oxygen to the muscle cell or altered oxidative phosphorylation by the mitochondria. The latter may be mediated by defective function of iron‐containing proteins crucial in oxidative phosphorylation and this is suggested both by the observation that treatment with iron, sufficient to correct the anaemia, does not completely reverse the metabolic changes and that there is a different time course for such metabolic improvements and the observed increase in haemoglobin concentration.
Non‐invasive techniques for assessing carbohydrate flux:
Authors: MURGATROYD P. R. , SONKO B. J. , WITTEKIND A. , GOLDBERG G. R. , CEESAY S. M. , PRENTICE A. M.
Published: December 2008

Glycogen forms the smallest yet most labile energy substrate store. Therefore studying carbohydrate flux may be crucial to understanding the regulation of energy balance. Indirect calorimetry has been used to measure carbohydrate oxidation overnight and during exercise in nine fasted subjects. Overnight carbohydrate oxidation (averaging 2.85 ± 0.8 g h‐1) was assumed to be derived primarily from hepatic glycogen since subjects were inactive or asleep, and since glucose oxidized after gluconeogenesis from protein is measured as protein oxidation. Lower‐limb muscle glycogen stores were depleted by repeated 30‐min periods of cycle ergometry at 45%Vo2max until exhaustion (8 ± 1 periods). The carbohydrate oxidation rate decreased as exercise progressed. Quadratic curves yielded a close fit to each individual's exercise carbohydrate depletion data (mean multiple correlation r= 0.9996) and provided excellent inter‐subject discrimination. Total (muscle plus liver) glycogen stores prior to exercise were estimated by extrapolation of the depletion curves to zero oxidation rate. This produced an estimate (174 ± 61 g) which compared well with predictions (208 ± 43 g) based on reference values for muscle mass and initial glycogen content. The results demonstrate that non‐invasive estimates of glycogen status can be obtained from accurate respiratory exchange data.
Endothelin contracts human uterine myometrium by a partly dihydropyridine‐sensitive mechanism
Authors: FRIED G. , LIU Y. A. , ANDERSSON E.
Published: December 2008

The effect of endothelin (ET), a recently discovered 21‐amino‐acid polypeptide with powerful vasoconstrictor properties, was examined on human uterine myometrial stripsin vitro. ET dose‐dependently (10‐‐11‐‐10‐‐7m) increased the contractile force (monitored as contraction amplitude) of the myometrium with significant effects at 10–8and 10‐‐7M. ET (10‐‐8m and up) also increased the basal tone of the myometrium.

The calcium channel blocking agents nifedipine (10‐‐7m) and diltiazem (10‐‐6m) both inhibited the spontaneous tonic contractions of the myometrium. When ET was given in the presence of nifedipine, the tonic contractions were further inhibited, whereas the ET‐induced increase in basal tone remained. The same result was obtained with diltiazem (10‐‐6m). The results indicate that the contractility of human myometrium may be modulated by ET, and that the effects of ET on the human myometrium are only partly mediated by dihydropyridine‐sensitive calcium channels.
5‐Hydroxytryptamine receptor characterizations of human cerebral, middle meningeal and temporal arteries: regional differences
Authors: JANSEN I. , OLESEN J. , EDVINSSON L.
Published: December 2008

We have studied the regional distribution of 5‐hydroxytryptamine (5‐HT) receptor subtypes in fresh circular segments of human cerebral, middle meningeal, and temporal arteries. Vasomotor responses induced by a series of 5‐HT agonists and antagonists with some degree of selectivity were studied by using a sensitivein vitrosystem.

Nine 5‐HT agonists were examined for contractile effects on the arteries. In cerebral and meningeal arteries 5‐carboxamidotryptamine (5‐CT) was more potent than 5‐HT. The opposite order of potency (5‐HT‐5‐CT) was found in temporal arteries. In the cerebral arteries 5‐methoxytryptamin (5‐MeOHT) was more potent than sumatriptan while sumatriptan was more potent than 5‐MeOHT in meningeal and temporal arteries.

The 5‐HT1, receptor antagonist, methiothepin, competitively antagonized 5‐CT‐induced contractions in cerebral arteries, with aPA2, value of 9.05. 5‐HT‐induced contractions were competitively antagonized by ketanserin (5‐HT2) in the temporal arteriesPA2, value of 9.06). Methiothepin and ketanserin had non‐competitive antagonistic effects in the middle meningeal arteries. The 5‐HT3, selective antagonist ondansetron did not cause any shift of the contractions induced by 2‐methyl‐5‐HT in the temporal, cerebral and middle meningeal arteries.

These results suggest that the cerebral arteries mainly contain 5‐HTid., or 5‐HT1,‐like receptors, and the temporal artery 5‐HT2, receptors; the data further indicate the presence of both receptor subtypes in the middle meningeal artery.
Dynamics of transcapillary fluid transfer and plasma volume during lower body negative pressure
Authors: LUNDVALL J. , BJERKHOEL P. , EDFELDT H. , IVARSSON C. , LÄNNE T.
Published: December 2008

Lower body negative pressure (LBNP) is a stimulus frequently used to study reflex circulatory responses in humans. Studies have provided data on LBNP‐induced blood pooling; however, the possibility that LBNP also might be associated with an important loss of plasma fluid has attracted little attention. Therefore this problem was analysed in male volunteers exposed to prolonged (10 min) high (70–75 mmHg) LBNP. Data on LBNP‐induced blood pooling that were more reliable than in previous literature were also provided.

LBNP caused early pooling of more than 870 ml of blood. Rapid filtration of plasma into the exposed tissues occurred throughout LBNP. The cumulative oedema in the legs and buttocks averaged as much as 460 ml, and additional quite large volumes of plasma apparently accumulated in other parts of the lower body. Concomitantly, there was compensatory absorption of extravascular fluid in the upper body. The net decrease in plasma volume (PV) was still large and averaged 491 2 29(SE) ml.

Two aspects of the demonstrated process of transcapillary fluid fluxes and PV decline may be emphasized. Firstly, in conjunction with the primary large redistribution of intravascular volume, it certainly implies that LBNP is a potent stimulus as also indicated by a progressive increase in heart rate (HR) and a progressive decline in systolic pressure throughout experimental intervention. In fact, LBNP‐induced circulatory stress clearly has bearings on the extreme hypovolaemic situation provided by the pressure‐bottle haemorrhage technique used in animals. Secondly, it not only offers an interesting example of the dynamics of PV but appears to have more general validity with regard to states characterized by gravitational shifts of blood (hydrostatic load), like upright exercise and quiet standing.
Lung to blood passage of albumin and a nona‐peptide after intratracheal instillation in the young developing pig
Authors: FOLKESSON H. G. , WESTRÖM B. R. , PIERZYNOWSKI S. G. , SVENDSEN J. , KARLSSON B. W.
Published: December 2008

The passage via the lower respiratory tract of the macromolecule, bovine serum albumin (BSA, mol. wt = 67000) and the nonapeptide, l‐deaminocysteine‐8‐d‐arginine vaso‐pressin (dDAVP, mol. wt = 1067), was assessed for 240 h after intratracheal instillation in young, developing pigs.

The plasma levels of immunoreactive BSA increased with time, reaching a maximum between 36–86 h after instillation, and the main portion of BSA in plasma appeared intact, as assessed by crossed immunoelectrophoresis. The dDAVP levels reached a maximum after 1–3 h. The time to reach maximal plasma levels increased with the age of the pig for BSA, while no such effect was observed for dDAVP. The total lung passage, as calculated by dividing the area under the plasma level‐time curve obtained after intratracheal instillation with that obtained after intravenous administration (elimination curve), showed no significant differences with age for BSA (21.8 ± 90% in the newborn, 15.1 ± 8.0% in the 2‐day‐old and 16.1±4.2% in the 70‐day‐old pigs). For dDAVP, a significant decrease in the total passage was obtained with age, from 74.6 ± 9.4% in the newborn pigs to 44.1 ± 13.3%, in the 2‐day‐old pigs (P < 0.001), and to 23.6 ± 7.1% (P< 0.01) in the 70‐day‐old pigs.

The study showed that the marker molecules, BSA and dDAVP, passed over the porcine lung into the blood circulation in high amounts, apparently inversely related to their molecular size. The total lung passage of dDAVP, but not that of BSA, was affected by changes with age, indicating that these two markers might traverse the lung epithelium via different routes that are differently affected during postnatal development.
Functional and biochemical effects of a K+‐ionophore on the isolated perfused rat heart
Authors: MARTINUSSEN H. J. , WALDENSTRÖMT A. , RONQUIST G.
Published: December 2008

Valinomycin, a K+‐specific ionophore, influenced function and metabolism of isolated, perfused rat hearts in a dose‐dependent fashion. At a concentration of 0.05 μg ml‐1 in perfusion fluid a 50% reduction of heart rate (HR) and a 90% reduction in max dP/dt were observed. These effects were paralleled by a substantial decrease of myocardial energy charge from about 0.80 to 0.20. A 2.5 fold increase in tissue lactate concentration indicated an increased rate of glycolytic activity. Low ATP combined with high ADP and AMP levels as found in these valinomycin‐treated hearts is known to promote phosphofructokinase activity and may explain the elevated lactate levels. A significant increase in the concentrations of adenosine, IMP and inosine was observed as well.