bluuebunny/crossref_metadata_2025 huggingface dataset:
Circadian periodicity in salivary carbonic anhydrase VI concentration
Authors: PARKKILA S. , PARKKILA A.‐K. , RAJANIEMI H.
Published: December 2008

Carbonic anhydrase VI (CA VI) is secreted into the saliva by the serous acinar cells of the parotid and submandibular glands. Saliva samples from six healthy male volunteers were analysed for concentrations of CA VI throughout the 24 h period by means of a specific time‐resolved immunofluorometric assay and the levels were compared with amylase activity. The sleeping period was from 00.10 h to 07.30 h and the subjects had breakfast at 07.30 h and regular meals at 13.30 h and 19.30 h. Saliva secretion decreased markedly during the sleeping period in all the subjects except one. The levels of both CA VI and amylase activity varied greatly among the subjects, but in a parallel manner, and declined to a very low level during the sleeping period. Dexamethasone intake at midnight had no effect on the morning rise in either enzyme. When the sleeping period was postponed from 06.10 h to 11.30 h both enzyme concentrations declined during the night and continued to be low until the subjects awoke at 11.30h, whereas salivary secretion was low only during the sleeping period. Our results suggest that CA VI secretion follows a circadian periodicity that is comparable to amylase secretion but independent of salivary secretion.
Vagal nerve stimulation of the guinea‐pig oesophagus
Authors: KERR K. P. , MITCHELSON F. , COUPAR I. M.
Published: December 2008

Vagal nerve stimulation of the isolated guinea‐pig oesophagus resulted in a triphasic contractile response which was abolished by tetrodotoxin. The mechanisms for each of the three responses were investigated. The first response was abolished by the neuromuscular blocking drug, tubocurarine, and was unaffected by atropine. The second response to vagal nerve stimulation was abolished by the ganglion blocking drug, hexamethonium, and by tubocurarine at a higher concentration than that required to block the first response. The second response was also abolished by atropine and was enhanced by physostigmine. It was concluded that this response was due to preganglionic stimulation of smooth muscle. ω‐Conotoxin GVIA selectively inhibited the third response. This response was resistant to the neuromuscular and ganglion blocking drugs yet was abolished by atropine and was enhanced by physostigmine. This implicates the involvement of cholinergic neurones activated independently of nicotinic ganglionic receptors. The third response was also selectively abolished by capsaicin and enhanced by thiorphan. Contractile responses resulting from exogenous substance P were abolished by atropine and tetrodotoxin and enhanced by physostigmine. These findings suggest that the third response may be mediated by the action of a substance P‐like neuropeptide released from sensory nerve endings which subsequently activate cholinergic neurones.
A new method for exchange of perfusion fluid during in vivo micropuncture
Authors: Micropuncture A new method for exchange of perfusion fluid during in vivo , MORSING P. , BRÄNNSTRÖM K. , PERSSON A. E. G. , SALOMONSSON M. , THORUP C.
Published: December 2008

The first step in the tubuloglomerular feedback (TGF) mechanism is postulated to be the sensing of changes in tubular NaCl concentration by the macula densa (MD) cells. Despite this, few in vivo studies using different tubular NaCl concentrations administered to the MD site have been completed. Methodological problems associated with retrograde perfusion might possibly explain this. In the present study we present a modification of a method used in in vitro tubular perfusion experiments which makes it possible to determine the TGF response using retrograde perfusion with a single perfusion pipette. The system is based on the use of a fluid exchange pipette introduced through a chamber in the holder of the perfusion pipette all the way to the tip of this pipette. The perfusion flow was regulated by a pressure head, and by regulating the outflow from the chamber. The flow was determined for different tip diameters and for different perfusion pressures. Using a tip diameter of 4 /tm, the flow through the tip was in the range 18–25 nL min‐1 at a pressure of 60–70 mmHg. The fluid‐exchange pipette was tested in vivo by measuring proximal tubular stop‐flow pressure while perfusing the macula densa region with different NaCl concentration.
Renal and haemodynamic effects of nitric oxide blockade in a Wistar assay rat during high pressure cross‐circulation of an isolated denervated kidney
Authors: BERGSTRÖM G. , RUDENSTAM J. , CREUTZ J. , GÖTHBERG G. , KARLSTRÖM G.
Published: December 2008

Blockade of NO synthesis with N‐ω‐nitro‐L‐arginine (L‐NNA) inhibits the vasodepressor response seen in intact Wistar assay rats in which isolated kidneys perfused via an extracorporeal circuit are perfused at high pressure. This study explores the renal and haemodynamic changes associated with this inhibition. Isolated kidneys (IK) were perfused at high pressure (175 mmHg) by a pump in series with intact Wistar assay rats in which blood pressure (BP), haemodynamics and renal function were studied. Nitric oxide (NO) synthesis was blocked by L‐NNA (2.5 mg kg‐1) in 13 experiments (175NO) while 14 control experiments (175C) were performed. IK was perfused at 90 mmHg in seven experiments (90C). The BP drop in the 175C assay rat was blocked by L‐NNA in 175NO (P < 0.01). However, when the blockade was reversed with L‐arginine infusion (20 mg kg J min“1) BP declined also in 175NO. Effective renal plasma flow (ERPF) and glomerular filtration rate (GFR) fell dramatically after L‐NNA in both the assay rat and in IK despite a high perfusion pressure. The marked increase in filtration fraction (FF) after L‐NNA suggests a dominating postglomerular vasoconstriction. The natriuretic response in IK to 175 mmHg was also markedly blunted by L‐NNA. We conclude that NO blockade inhibits the renomedullary depressor mechanism probably by restricting renal blood flow, and also blunts the pressure induced natriuretic response as a result of a reduced sodium filtration. Finally, the autoregulation of whole kidney blood flow seems to be more efficient although set at a higher level of vasoconstriction.
Energetics of fish larvae, the smallest vertebrates
Authors: WIESER W.
Published: December 2008

In this review recent findings on the energetics offish larvae are presented, highlighting some of the physiological problems linked to small body size. The existence of a mass‐independent phase of specific metabolic rate is confirmed but it is pointed out that in young fish ontogenetic transitions of metabolic scaling have so far been documented only for the routine level of activity. Maximum metabolic rate is limited by mitochondrial density in the swimming muscles which scales with a mass exponent of ˜ 0.9. Mitochondrial density in the swimming muscles of a species of fish, from larva to adult, covers about the same range as mitochondrial density in the skeletal muscles of mammals. However, the aerobic capacity (power density) of mitochondria is one order of magnitude lower in fish than in mammals. Energy metabolism in embryos and early larvae of fish is almost entirely aerobic. Anaerobic power in the fast muscle fibres is low after hatching but increases during the transition from larva to Juvenile with a mass exponent greater than one. In hypoxic water fish larvae swim more economically (i.e. their cost of transport is lower) than in normoxic water. If the rate of growth exceeds a critical threshold (about 10% d‐1) fish larvae are capable of increasing the apparent efficiency of growth, probably by reducing the costs of other energy‐consuming functions of maintenance.
Skeletal muscle metabolism during short duration high‐intensity exercise: influence of creatine supplementation
Authors: BALSOM P. D. , SÖDERLUND K. , SJÖDIN B. , EKBLOM B.
Published: December 2008

Seven male subjects performed repeated bouts of high‐intensity exercise, on a cycle ergometer, before and after 6 d of creatine supplementation (20 g Cr H2O day‐1). The exercise protocol consisted of five 6‐s exercise periods performed at a fixed exercise intensity, interspersed with 30‐s recovery periods (Part I), followed (40 s later) by one 10 s exercise period (Part II) where the ability to maintain power output was evaluated. Muscle biopsies were taken from m. vastus lateralis at rest, and immediately after (i) the fifth 6 s exercise period in Part I and (ii) the 10 s exercise period in Part II. In addition, a series of counter movement (CMJ) and squat (SJ) jumps were performed before and after the administration period.

As a result of the creatine supplementation, total muscle creatine [creatine (Cr) + phosphocreatine (PCr)] concentration at rest increased from (mean + SEM) 128.7 (4.3) to 151.5 (5.5)mmolkg_1 dry wt (P < 0.05). This was accompanied by a 1.1 (0.5) kg increase in body mass (P < 0.05). After the fifth exercise bout in Part I of the exercise protocol, PCr concentration was higher [69.7 (2.3) vs. 45.6 (7.5) mmol kg“‘ dry wt, P < 0.05], and muscle lactate was lower [26.2 (5.5) vs. 44.3 (9.9) mmol kg”1 dry wt, P < 0.05] after vs. before supplementation. In Part II, after creatine supplementation, subjects were better able to maintain power output during the 10‐s exercise period (P < 0.05). There was no change in jump performance as a result of the creatine supplementation (P > 0.05).

These findings show that enhanced fatigue resistance during short duration high‐intensity exercise following creatine supplementation is associated with a greater availability of PCr and a lower accumulation of lactate in the muscle. The finding that jump performance was not enhanced suggests that short‐term creatine feeding does not influence peak power output.
Toxin of the marine alga Prymnesium patelliferum enhances voltage dependent Ca2+‐currents, elevates the cytosolic Ca2+‐concentration and facilitates hormone release in clonal rat pituitary cells
Authors: KOLDERUP J. , MELDAHL A.‐S. , ERIKSEN S. , HAUG E. , FONNUM F. , SAND O.
Published: December 2008

The marine flagellate Prymnesium patelliferum produces toxins lethal to fish. The toxin extracted from the alga has haemolytic, cytotoxic and neurotoxic effects, but the action mechanisms of the toxin are not known in detail. We have examined the toxin effects on the voltage sensitive Ca2+‐currents, the cytosolic Ca2+‐level ([Ca2+]1) and the prolactin release in clonal rat anterior pituitary GH4C1 cells, which possess T‐ and L‐type Ca2+‐channels. The trans‐membrane Ca2+‐current was recorded using whole‐cell voltage clamp. After 5–15 min exposure to the algal toxin at a final concentration of 50000–100000 cells mL‐1, the Ca2+‐currents through both the T‐ and L‐channels showed a 2–3‐fold enhancement. The voltage sensitivity of the Ca2+‐currents was not affected by the algal toxin, and the toxin‐induced currents were inhibited by 100 μM of the Ca2+‐channel blocker D‐600. In toxin‐exposed cells microfluorometric measurements based on fura‐2 revealed an increase of [Ca2+]1 from 100–150 to 300–500 nM. This elevation was delayed and partially inhibited by 100 μM D‐600. The algal toxin induced prolactin release in a dose‐dependent manner, and this effect was inhibited by the Ca2+‐channel blocker verapamil. We therefore conclude that the toxin of P. patelliferum affects the Ca2+ homeostasis of the pituitary cells by increasing the leak through voltage sensitive Ca2+‐channels, resulting in increased [Ca2+]1 and secretion of prolactin.
The migrating motor complex‐the motor component of a cholinergic enteric secretomotor programme?
Authors: MELLANDER A. , ABRAHAMSSON H. , SJÖVALL H.
Published: December 2008

The role of cholinergic nerves in the cyclic activation of interdigestive motility and secretion was studied in 23 healthy volunteers. Net fluid transport in a distal duodenal segment and the release of pancreaticobiliary secretions into the duodenal lumen, were measured with a triple lumen perfusion technique. Interdigestive motor activity was recorded with a low‐compliance pneumohydraulic system, and the transmural potential difference (PD) was measured as an on‐line marker of electrogenic anion secretion. Transport parameters were related to the migrating motor complex (MMC) in the control situation and after the administration of atropine (0.01 mg kg‐1 body wt, i.v.).

The early part of the MMC cycle was characterized by low motor activity, low release of bile and pancreatic juice into the duodenal lumen, a slightly lumen positive transmural PD, and a non‐significant net fluid absorption (‘absorptive mode’)‐ Under control conditions, motor activity and pancreaticobiliary secretions subsequently increased and there was a shift in net fluid transport and transmural PD in the secretory direction (‘secretory mode’). Furthermore, there was a significant correlation between contraction frequency, a more lumen negative PD, and the magnitude of net fluid secretion. After the administration of atropine, the secretory mode was abolished, but there was still a significant correlation between contraction frequency and transmural PD.

In conclusion, cholinergic neurones seem to mediate the shift from the absorptive to the secretory mode in the human distal duodenum. The antisecretory effect of atropine may be the result of inhibition of motilin release, reduced activation of tension‐sensitive intramural secretory pathways, or blockade of cholinergic neurones to the secreting epithelium.
Rate of active tension development from rigor in skinned atrial and ventricular cardiac fibres from swine following photolytic release of ATP from caged ATP
Authors: MORANO I. , ÖSTERMAN Å. , ARNER A.
Published: December 2008

We investigated the rate of tension development (ktd) after photolytical release of ATP from, P3‐l‐(2‐nitrophenyl)‐ethyladenosine‐5′‐triphosphate (‘caged ATP’) of atrial and ventricular fibre bundles from pig. Contraction was initiated from high‐tension (HT) and low‐tension (LT) rigor at maximal Ca2+ activation (pCa 4.5). The ktd of atrial fibre bundles was 6.8 s_1 from LT and 6.9 s_1 from HT rigor. Rate of tension development of ventricular fibre bundles was significantly lower (P < 0.001) being 1.06 s“1 and 0.94 s”1 from LT and HT rigor, respectively. The ktd of skinned ventricular fibre bundles incubated in a high [K+], low [Ca2+] (cardioplegic) solution prior to the skinning procedure decreased significantly (P < 0.05) to 0.73 s‐1 and 0.63 s_1 from LT and HT rigor, respectively, whereas that of skinned atrial fibre bundles remained at 7.1 s‐1 and 6.9 s‐1 from LT and HT rigor, respectively. Phosphorylation levels of the myosin light chain 2 isoform in the atrial fibre bundles (ALC‐2) was 15.6±2.7%. The corresponding values for the two ventricular isoforms, VLC‐2 and VLC‐2*, were 31.2 ± 0.4% and 25.1 ±2.1%, respectively. Phosphorylation levels of fibre bundles incubated in cardioplegic solution prior to skinning were 11.6%, 18.9%, and 15.4% of the ALC‐2, VLC‐2 and VLC‐2*, respectively. The results show that the rate of tension development is more than seven‐fold higher in the atrial compared with ventricular fibre bundles. These results correlate with the differences in ATPase activity of the contractile proteins in solution and, most likely, reflect differences in the myosin isoform composition. In ventricular fibre bundles the increased levels of light chain phosphorylation were associated with increased rate of contraction.
Prostacyclin aerosol and inhaled nitric oxide fail to reverse pulmonary vasoconstriction induced by thromboxane analogue in dogs
Authors: WELTE M. , ZWISSLER B. , HABLER O. , KLEEN M. , MESSMER K.
Published: December 2008

Inhalation of either prostacyclin (PGI2) as an aerosol or nitric oxide (NO) has been shown to elicit selective pulmonary vasodilation during hypoxic pulmonary vasoconstriction in dogs. Hypoxia may produce cardiovascular changes confounding interpretation of drug effects. Therefore, we investigated the effects of PGI2‐aerosol and inhaled NO (50 p.p.m.) on pulmonary pressure‐flow relationships (P/Q_plots) during thromboxane analogue (U46619) induced pulmonary vasoconstriction.

In eight anaesthetized dogs infusion of U46619 (0.33 ± 0.18 μg kg_1min‐1) increased the slope (3.5 ± 1.1 to 8.4 ± 1.7 mmHg L‐1min‐1,P <0.001) and the intercept (4.4±2.3 to 10.2 ± 4.6 mmHg,P <0.01) ofP/Qplots indicating pulmonary vasoconstriction. Inhalation of both aerosolized PGI2solution (10μgmL‐1) and NO (50 p.p.m.) reduced neither the slope nor the intercept of theP/Q_plots. Increasing the concentration of the aerosolized PGI2solution to 50 μg mL‐1:(n= 3) did not enhance the effect on pulmonary circulation but systemic vascular resistance fell by 23%. Oxygenation and intrapulmonary shunt remained unchanged during both PGI2‐aerosol and inhaled NO. The failure of PGI2‐aerosol to induce pulmonary vasodilation indicates that during aerosolization PGI2‐concentrations at receptor sites on pulmonary vessels were insufficient to surmount U46619 induced vasoconstriction; this notion is supported by unchanged arterial plasma concentrations of the PGI2degradation product 6‐keto‐PGFlα. Considering that NO inhaled at comparable concentrations in sheep reversed U46619 induced pulmonary vasoconstriction, species differences may account for the failure of both PGI2‐aerosol and NO to dilate pulmonary vessels in dogs.
Modulation of vascular contractile responses to α1‐and α2‐adrenergic and neuropeptide Y receptor stimulation in rats with ischaemic heart failure
Authors: BERGDAHL A. , VALDEMARSSON S. , PANTEV E. , OTTOSSON A. , FENG Q.‐P‐ , SUN X‐Y. , HEDNER T. , EDVINSSON L.
Published: December 2008

In order to evaluate adaptational changes in vascular function in congestive heart failure (CHF), we studied the contractile responses of isolated arterial and venous blood vessels from rats suffering from CHF induced by coronary artery ligature, resulting in a myocardial infarction. The contractile responses of the basilar, femoral and renal arteries and of the iliac vein were examined in relation to adrenergic and neuropeptide Y (NPY) receptor function by the action of the α1 agonist phenylephrine, the α2 agonist clonidine and NPY. The contractile force was measured (in mN) and in% of K+‐induced contraction as well as pD2 to each agonist. When stimulated by a 60 mM K+‐buffer solution, the femoral and renal arteries from CHF rats responded with a stronger contraction (Emax; 9.4 ± 0.6 and 9.8 ± 0.6mN) than the corresponding Sham vessels (Emax; 6.2 ± 0.7 and 5.6 ± 0.4 mN respectively, P < 0.001). On the contrary, the iliac vein of CHF responded less to K+ than the Sham iliac vein (Emas 2.5 ± 0.2 and 3.7 ± 0.5 mN, P < 0.01). The CHF iliac vein responded with a weaker contraction when stimulated with phenylephrine (Emax 1.9 ± 0.4 mN) and showed a lower sensitivity (pD2 5.6 ± 0.1) than the corresponding sham vessel (Emax 5.7 ± 2.3mN and pD2 6.3 ± 0.5, P < 0.05). The CHF renal artery was less sensitive to clonidine (pD2 6.4 ± 0.6) than the Sham renal artery (pD2 7.2 ± 0.1, P < 0.05). The results indicate differences between CHF and Sham vessel segments according to both contractile capacity induced by K+‐depolarization and to agonist induced contractile capacity and sensitivity. The differences are not of general nature but vary according to the vascular bed examined.
Differences in binding of platelet factor 4 to vascular endothelium in vivo and endothelial cells in vitro
Authors: HANSELL P. , OLOFSSON M. , MAIONE T. E. , ARFORS K.‐E. , BORGSTROM P.
Published: December 2008

The binding of fluorescein‐labelled recombinant human platelet factor 4 (rhPF4) to the vasculature of the hamster cheek pouch in vivo was compared with that to cultured endothelial cells (EC) from human umbilical veins (HUVEC) and arteries (HUAEC) and from human aorta (HAEC).

In vivo data: systemically injected rhPF4 rapidly disappeared from plasma in a biphasic pattern (t1= 2 and 41 min). High intensity non‐uniform binding of rhPF4 occurred at short specific sites along both arterioles and venules. The length of the intense sites was 76 + 46/xm and their frequency was 10 ± 4 per cm2 cheek pouch. Heparin was injected at 4 and 9 min, but not 30 min, post‐rhPF4 displaced most of the high intensity labelling indicating internalization with time. Neither pretreatment with more than 50‐fold excess of unlabelled rhPF4 nor histamine‐ or LTB4‐induced vascular macromolecular leakage changed the frequency of short intense sites.

In vitro data: uniform time‐dependent intense binding of rhPF4 occurred in a similar fashion in subconfluent HUVEC, HUAEC and HAEC. All cell types showed nuclear staining, demonstrating internalization. When heparin was given to EC prior to rhPF4, binding was delayed in time but not blocked.

In conclusion, rhPF4 does not bind uniformly with high intensity along pre‐ and post‐capillary vessels of the hamster cheek pouch in vivo as predicted by the rhPF4‐labelling of subconfluent (migrating/proliferating) human EC in vitro. The short infrequent sites of intense rhPF4‐labelling in vivo may represent regions of endothelial cell migration/proliferation similar to subconfluent EC in culture.
Effect of pre‐treatment with desferrioxamine and mannitol on radical production and kidney function after ischaemia‐reperfusion. A study on rabbit kidneys
Authors: HARALDSSON G. , SORENSEN V. , NILSSON U. , PETTERSSON S. , RASHID M. , SCHERSTÉN T. , ÅKERLUND S. , JONSSON O.
Published: December 2008

The effects of pre‐treatment with mannitol and the iron chelator desferrioxamine on oxygen radical formation and glomerular and tubular function after ischaemia in the rabbit kidney were studied. Radicals were measured with ESR and spin trapping. At reperfusion after 60 min of renal ischaemia there was a significant increase in the production of free radicals in the venous effluent from the kidney. Administration of either mannitol or desferrioxamine given before ischaemia and before recirculation reduced the radical production significantly. The iron chelator appeared to be more effective. Glomerular function measured 48 h after reperfusion was significantly better after pretreatment with desferrioxamine and mannitol compared with mannitol alone. Tubular function did not differ between the two pre‐treatment groups.
Effects of endurance training on left ventricular performance: a study in anaesthetized rabbits
Authors: HEXEBERG E. , WESTBY J. , HESSEVIK I. , HEXEBERG S.
Published: December 2008

Endurance training is known to increase ventricular performance during exercise and to decrease resting heart rate. The aim of this study was to evaluate a model for endurance training in rabbits and to study the effects of endurance training on local myocardial performance in the left ventricle during resting conditions. One group of rabbits underwent a 10‐week exercise training programme. The rabbits trained 5 days a week on a treadmill. Training periods increased gradually from 15 min to 1 h with increments in speed from 0.5 to 1.2 km h1. After the training programme the rabbits were anaesthetized and studied as acute open‐chest preparations. A micro‐tip pressure transducer was introduced via apex to the left ventricle and two pairs of ultrasonic crystals were implanted in the left anterior wall to measure segment lengths. One pair measured shortening in the circumferential direction whereas the other pair measured shortening in the longitudinal direction. Heart rate was lower in the trained group (n = 5), 172 + 9 beats min“‘ (mean±SEM), compared with 235 ± 19 beats min ’ in the control group (n = 8) (P < 0.02). Stroke volume, measured by radio‐nuclidelabelled microspheres, was greater in the trained rabbits compared with controls (P < 0.03). Shortening in both segments was of similar magnitude for the trained and control groups. End‐systolic pressure‐length relations (ESPLR) obtained by occlusion of the descending aorta (balloon catheter) showed reduced slopes for longitudinal segments in the trained group compared with the control group (P < 0.05). We conclude that this endurance training programme in rabbits can be used to study myocardial effects of endurance training. Furthermore, the less steep slope of ESPLRs for the longitudinal segment in the trained animals might indicate a structural myocardial remodelling and increased contractile reserve that might be recruited during adrenergic stimulation in the trained group.
Endothelin infusion reduces hypoxic pulmonary hypertension in pigs in vivo
Authors: LISKA J. , HOLM P. , ÖWALL A. , FRANCO‐CERECEDA A.
Published: December 2008

Previous work has shown that the plasma levels of the potent vasoactive peptide endothelin (ET) are increased in pathophysiological conditions with increased pulmonary vascular resistance and it has been speculated that ET may play some part in hypoxic pulmonary hypertension. We have therefore evaluated the effects of ET‐infusion in the porcine pulmonary circulation after hypoxia‐induced hypertension.

Pigs under general anaesthesia were artificially ventilated through an endotracheal tube and hypoxia was induced by decreasing the fraction inhaled 02 from 0.21 to 0.10. Haemodynamic parameters were continuously recorded using a Swan‐Ganz catheter in combination with thermodilution for cardiac output measurements. ET‐1 or ET‐3 was given as an i.v. infusion through the Swan‐Ganz catheter in the right ventricle.

Hypoxia induced a reproducible increase in pulmonary vascular resistance (PVR), mean pulmonary artery pressure (MPAP) and right ventricular stroke work (RVSW) while the systemic vascular resistance (SVR) slightly decreased. Cumulative infusion of ET‐1 (10, 25 and 50 ng kg‐1 min‐1) dose‐dependently decreased MPAP and PVR; at a higher dose (100 ng kg‐1min‐1), the PVR returned to the level observed at hypoxia. ET‐infusions at 50 and 100 ng kg‐1 min‐1 evoked an increase in SVR and a decrease in cardiac output (CO) and stroke volume (SV). RVSW also gradually decreased during ET‐1 infusion. Infusion of ET‐3 evoked effects similar to those of ET‐1 infusions, although the response to ET‐3 was not that rapid in onset. In a second series of animals, repeated 15 min periods of hypoxia evoked a stable, reproducible response with a consistent increase in PVR, MPAP and RVSW which returned to baseline values during normoxia. Infusion of ET‐1 (25 ng kg‐1 min‐1) evoked a rapidly developing decrease in PVR and MPAP which was quickly normalized upon cessation of the ET‐infusion. ET‐1 infusion at this concentration did not per se influence the haemodynamic parameters during normoxia.

It is concluded that in the pig, short‐term ET‐infusion reduces the pulmonary hypertension associated with acute hypoxia.
Cardiovascular response to exercise in humans following acclimatization to extreme altitude
Authors: SAVARD G. K. , ARESKOG N.‐H. , SALTIN B.
Published: December 2008

The purpose of this study was to assess the effects of acclimatization to extreme altitude on the cardiovascular system, using vagal and adrenergic blockade and acute restoration of normoxia during exercise to maximum with one and two legs. Fourteen climbers on an expedition to the Himalayas were studied at a lower base camp (5250 m) following 56–81 days at altitudes between 5250 and 8700 m. After acclimatization, peak heart rate (HRpeak), oxygen uptake (o2k) and noradrenaline (NA) were similar during maximal one‐ and two‐legged cycling, whereas peak plasma lactate was higher during the one‐legged protocol. HRpeak (range 113–168 beats min“1) was lowest when subjects returned from the higher camps. The degree of partial restoration of HRpeak to more normal values within seconds of 60% 02 inhalation (range 5–35 beats min˜l HRpeak increase) was greatest in subjects with low HRpeak. HR responses to /?‐l blockade increased as a function of HRpeak and the HR responses to atropine were the least in subjects with high HRpeak‐ These findings suggest that (a) the reduction in HRpeak is linked to the duration and severity of the hypoxaemia, (b) the degree of restoration of HRpeak with acute normoxia is dependent on the level of attenuation or down‐regulation of cardiac sympathetic activation (SNA), (c) cardiac vagal drive is masked to a lesser extent in chronic hypoxia because of attenuated SNA and lower HRpeak values, and (d) the lower blood lactate levels at altitude is a function of muscle mass involvement rather than adrenergic activation, as normal peak values were reached during exercise with a small muscle mass.
Muscle fibre type and dimension in genetically obese and lean Zucker rats
Authors: HE DONG , BOLSTAD GRETA , BRUBAKK ALF , MEDBØ JON INGULF
Published: December 2008

Skeletal muscle structure and morphology may be altered in obesity. To study this further, muscles from six genetically obese (fa/fa) and six normal male rats were examined at 15 weeks of age. The gluteus medius, vastus lateralis and rectus abdominis muscles were dissected out and stained for histochemical fibre typing. In addition the fibre cross‐sectional area was measured on a graphic tablet. The proportion of fast twitch fibres was larger in the vastus lateralis and rectus abdominis muscles of the obese rats (P<0.01); no difference was seen for the gluteus medius muscle. For the normal rats the cross‐sectional area of the fast‐twitch fibres was 2–3 times larger than the area of slow‐twitch fibres in the same muscle. The cross‐sectional area of the fast‐twitch fibres in the obese rats was 40–47% less than in the control animals (P<0.003), while no difference between the two groups was found for the slow‐twitch fibre area. The data thus suggest that in the genetically obese rats the development of fast‐twitch fibres was primarily affected. Moreover, in these animals some muscles may be more affected than others.
Sympathetic nervous system effects on feline bladder wall compliance throughout continence
Authors: KHADRA M. H. , SATCHELL P. M. , VAUGHAN C. W.
Published: December 2008

The urinary bladder is a compliant organ, high compliance being essential for useful urine storage. The extent to which the sympathetic nervous system promotes the storage of urine by increasing bladder compliance is unclear. The aim of the present study was to determine the range of bladder volumes over which the sympathetic nervous system was to determine the range of bladder volume over which the sympathetic nervous system increased bladder wall compliance. In supine, anaesthetized cats, the bladder was filled at twice the rate of natural filling, the continence cycle being interrupted at five stages. These stages were when the bladder had become globular, during prodromal contractions, soon after non‐micturating contractions had commenced approximately two‐thirds of the way through the continence cycle and just prior to micturition. During each of these interruptions, bladder volume was held constant while pelvic nerve afferent activity and bladder pressure were recorded. Recordings were obtained before and during the intravenous infusion of trimethaphan, the resulting partial ganglion blockade decreasing arterial pressure by a third. Bladder pressure as well as afferent blocked, indicating that there had been a prevailing net sympatho‐inhibitory effect promoting bladder wall relaxation. This effect was observed during prodromal contractions and continued until the onset of micturition. This net sympatho‐inhibitory effect is a potential therapeutic path for the treatement of bladder storage disorders.
Measurement of the total concentration of functional Na+, K+‐pumps in rumen epithelium
Authors: KRISTENSEN N. B. , HANSEN O. , CLAUSEN T.
Published: December 2008

Using the technique of vanadate‐facilitated [3H]ouabain binding we have developed a simple and reliable assay for measuring the concentration of [3H]ouabain binding sites in small fresh or frozen biopsies of rumen epithelium papillae. In bovine and ovine rumen epithelium obtained from the cranio‐ventral rumen sac the concentration of [3H]ouabain binding sites was 1.6‐4.9 nmol g dry wt‐1 (n= 32) and 3.7‐5.2 nmol g dry wt‐1 (n= 6), respectively. When incubated in oxygenated Krebs‐Ringer bicarbonate buffer fresh biopsies of rumen epithelium maintained a high K+ and low Na+ content for at least 6 h. Na+ loading of the biopsies induced about 20‐fold increase of the Na+, K+‐pump activity based on measurement of ouabain suppressible net [86Rb+] influx. The ouabain suppressible net influx of [86Rb+] measured in Na+ loaded biopsies showed a close correlation to the [3H]ouabain binding capacity (r= 0.80, P < 0.01) and corresponded to 47pL2% (n= 9) of the theoretical maximum flux rate. The ouabain suppressible net influx of K+ and [86Rb+] were linearly related (r= 0.73; P < 0.001). The net Na+ efflux was 1.21 times the net K+ influx. It is concluded that rumen epithelium has a large capacity for active Na+/K+ transport and that there is agreement between the concentration of [3H]ouabain binding sites in the epithelium and the ouabain suppressible rate of net [86Rb+] influx in Na+ loaded biopsies in spite of some uncertainty about the maximum turnover number of the Na+, K+‐pump in rumen epithelium.
Facilitation of the human nociceptive reflex by stimulation of Aβ‐fibres in a secondary hyperalgesic area sustained by nociceptive input from the primary hyperalgesic area
Authors: ANDERSEN O. K. , GRACELY R. H. , ARENDT‐NIELSEN L.
Published: December 2008

Hyperalgesia was induced in healthy volunteers by topical capsaicin applied on the dorsum of the foot within the receptive field of the sural nerve. Under presence of hyperalgesia different normally non‐noxious conditioning stimuli were applied to the hyperalgesic area and the polysynaptic nociceptive spinal reflex and pain ratings were used to assess central excitability. The nociceptive reflex was measured in the knee extensor and flexor muscles evoked by electrical stimulation of the sural nerve trunk at an intensity of 1.5 times the initial reflex threshold (an intensity above the pain threshold). Thermal stimulation of the primary hyperalgesic area (re)established both on‐going spontaneous pain and secondary hyperalgesia. Thus, increased nociceptive reflexes were recorded and increased pain intensity reported when Aβ‐fibres in the secondary hyperalgesic area were activated concurrently with the reflex testing after a non‐noxious thermal stimulation of the primary hyperalgesic area. The Aβ‐fibre activation was achieved by continuous low‐intensity electrical stimulation (40 Hz) that was initiated after on‐going pain produced by the thermal stimulation had waned. The same measurement without prior thermal conditioning stimulation of the primary area resulted in no reflex facilitation, indicating rapid changes in the central excitability with existence of on‐going nociceptive activity. This indicates that the development and maintenance of secondary hyperalgesia are dependent on sustained peripheral nociceptive activity. The study also shows that a central summation of nociceptive and non‐nociceptive afferent activity can occur once secondary hyperalgesia is present.
Sodium and dopamine excretion in prehypertensive Dahl rats during severe hypervolaemia
Authors: MÖLLER B. , HANSELL P.
Published: December 2008

As opposed to the salt‐resistant Dahl‐R rat the salt‐sensitive Dahl‐S has a defective renal dopamine DA1, receptor that may be involved in its susceptibility to develop hypertension during a high salt diet. To compare the ability of prehypertensive Dahl‐R and Dahl‐S to respond to a severe isotonic sodium load, renal function was monitored during a severe form of acute isotonic volume expansion (10% VE). Mean arterial blood pressure before VE was similar in Dahl‐R and Dahl‐S and decreased in both strains by 6% during VE. The accumulated sodium excretion during VE in Dahl‐R was 411 ± 64 μmol 100 min1g1kidney wt (kw) which was not different from that in Dahl‐S (420±95 μmol 100min‐1g‐1kw). The accumulated dopamine excretion (a mirror of renal dopamine synthesis) during VE was also similar in Dahl‐R (134±13 ng 100 min‐1g1kw) and Dahl‐S (126 ± 16 ng 100 min1g‐1kw). The excretion of DOPAC, the main metabolite of Dahl‐S, glomerular filtration rate and systemic haematocrit did not differ between the strains before, during or after VE. To conclude, in spite of a defective renal DA1, receptor prehypertensive Dahl‐S do not respond with an attenuated natriuretic or dopamine excretory response when subjected to a severe isotonic sodium load. The results do not support a sodium retaining role over a defective DA1, receptor in the salt‐sensitive hypertension in Dahl‐S.
Effects of endothelins on renin secretion from rat kidneys
Authors: SCHOLZ H. , KRÄMER B. K. , HAMANN M. , GÖTZ K.‐H. , KURTZ A.
Published: December 2008

Using a preparation of isolated rat kidneys perfused at constant renal artery pressure (80 mmHg) we investigated the role of endothelins in the regulation of renin release. Addition of three related endothelins (ET‐1, ET‐2, ET‐3) at a concentration of 10 pmol L‐1tended to enhance renin secretion rates. Higher doses (100 pmol L‐1, 1 nmol L‐1) of different ETs such as the selective ETB, receptor agonist sarafotoxin S6c (100 pmol L‐1, 1 nmol L‐1) inhibited renin release and increased renal vascular resistance with similar potency. These effects of ETs were blunted when calcium ions were removed from the perfusate. Renin release activated by isoproterenol (10 nmol L‐1) was also significantly reduced with ET‐1, ‐2 and ‐3 (1 nmol L‐1). BQ‐123 (500 nmol L‐1), a selective ETAreceptor antagonist, only attenuated, whilst the nonselective ET receptor blocker bosentan (Ro 47–0203, 10 μmol L‐1) almost abolished the renal vasopressor and renin inhibitory action of ET‐1 and sarafotoxin S6c. BQ‐123 and bosentan alone did not affect either perfusate flow or basal renin secretion rates in isolated perfused kidneys. These findings indicate that all three ET peptides equipotently inhibit renin secretion from the kidneys. Most of the vasopressor and renin inhibitory effect of ETs is mediated by ETb, rather than ETAreceptors involving a calcium‐dependent signal transduction mechanism. Moreover, our results suggest that intrarenally released ETs do not contribute to the regulation of renin secretion from isolated perfused rat kidneys.
Efferent renal nerve stimulation inhibits the antihypertensive function of the rat renal medulla when studied in a cross‐circulation model
Authors: RUDENSTAM J. , BERGSTRÖM G. , GÖTHBERG G. , KARLSTRÖM G.
Published: December 2008

The aim of this study was to investigate the effects of renal nerve stimulation on the humoral renal antihypertensive system. An isolated kidney (IK) was perfused at normal or high arterial pressures from a normotensive assay rat by means of a perfusion pump. Perfusion pressure (PP) to the IK was 90 mmHg for a control period of 30 min. In three of five experimental groups PP was then increased to 175 mmHg. In two of the groups the renal nerves were stimulated at 2 (P‐1752Hz) or 5 Hz (P‐1755Hz) for 60 min. The remaining group served as a control (P‐175c). In two groups IK pressure was maintained at 90 mmHg with 5Hz nerve stimulation (P‐905Hz) or without nerve stimulation (P‐90c). MAP of the assay rat decreased by 22 and 27% (P < 0.001) in the P‐175c and P1752Hz groups, respectively during the 60 min period of nerve stimulation, but remained stable in P‐1755Hz. Renal blood flow increased in the IK when PP was increased in P‐175c, but did not change significantly in P‐1752Hz or P‐1755Hz. Blood pressure remained constant in the assay rat when the IK was perfused at 90 mmHg. The renal excretory functions of the IK decreased in a frequency dependent manner by 2 and 5 Hz renal nerve stimulation compared with P‐175c. We conclude that 5 Hz renal nerve stimulation inhibits the pressure dependent release of humoral depressor substances from an IK perfused at 175 mmHg, whereas this is not seen when stimulating at 2 Hz. It is suggested that the release of antihypertensive substances from the renal medulla requires an increased renomedullary blood flow.
Myosin heavy chains in skeletal muscles of the common shrew (Sorex araneus): absence of a slow isoform and transitions of fast isoforms with ageing
Authors: SAVOLAINEN J. , VORNANEN M.
Published: December 2008

Myosin heavy chain (MHC) composition in seven skeletal muscles of the common shrew (Sorex araneus) was analysed by gradient SDS‐PAGE and immunoblotting with monoclonal antibodies. Characteristic for the studied muscles (diaphragm, lateral gastrocnemius, medial gastrocnemius, masseter, plantaris, soleus and tibialis anterior) was a total absence of the slow isoform, MHCI; all muscles were exclusively composed of two fast isoforms MHCIId and MHCIIb. In young adults the amount of MHCIId varied between 34% (tibialis anterior) and 97% (masseter). In over‐wintered senescent individuals MHCIId was clearly the dominant isoform in all muscles studied; the lowest MHCIId content was measured for tibialis anterior (69%), while in diaphragm, masseter and soleus it was practically the sole isoform (over 96%). Ageing associated isoform transition from MHCIIb to MHCIId occurred in all seven muscles studied (P< 0.05).
The NO synthase inhibitor l‐NNA depresses neurohypophysial vasopressin but not its precursor amidating enzymes in salt‐loaded rats
Authors: SKUJINS A. , THORN N. A.
Published: December 2008

The arginine vasopressin (AVP) producing hypothalamo‐neurohypophysial system also has high activities of NO‐synthase. Vasopressin production and secretion is drastically upregulated during salt intake and the NO‐producing enzyme may be involved. We have studied the influence of the NO‐synthase inhibitor NG‐nitro‐l‐arginine (l‐NNA on neurohypophysial and hypothalamic AVP and its amidating enzymes in salt‐loaded and control rats as well as on stimulated AVP release in vitro in such rats. Rats were given 2% NaCl solution as the only fluid for 4 days and then returned to tap water. The specific amount of AVP (μg (mg protein)‐1) and the activities of peptidylglycine α‐ hydroxylating monooxygenase (PHM) and peptidyl‐α‐hydroxyglycine α‐amidating lyase (PAL), components of its amidating processing enzyme in the supraoptic (SON) and paraventricular nuclear (PVN) regions, did not change during the salt‐loading or the following recovery period. In contrast, the AVP and PHM and PAL in the neurohypophysis fell drastically during the salt loading. After that, PHM and PAL increased even more rapidly than AVP, the latter reaching control levels in about 10 days. Salt loading did not change the protein content of the neurohypophysis. When salt loading was performed after administration of l‐NNA, the neurohypophysial AVP at the end of the salt loading and 3 days later was lower than in rats not receiving l‐NNA, whereas PHM and PAL were not affected. Fractional AVP release from isolated neurohypophyses of salt loaded rats treated with l‐NNA and stimulated with K+ was similar to that found in non‐treated rats. It is suggested that l‐NNA may affect translation or precursor processing of AVP.
Regional differences in endothelium‐dependent relaxation in the rat: contribution of nitric oxide and nitric oxide‐independent mechanisms
Authors: ZYGMUNT P. M. , RYMAN T. , HÖGESTÄTT E. D.
Published: December 2008

Relaxant effects of acetylcholine (ACh), histamine, calcitonin gene‐related peptide (CGRP) and the calcium ionophore A23187 were examined in rat femoral (Ø ≅ 0.2 mm), mesenteric (0.2 mm), intrarenal (0.2 mm) and hepatic (0.3 mm) arteries, and aorta (2 mm). Acetylcholine elicited an endothelium‐dependent relaxation in all arteries. Histamine induced an endothelium‐dependent relaxation in aorta, and mesenteric and intrarenal arteries, whereas a partly endothelium‐dependent and mainly endothelium‐independent relaxation was observed in hepatic and femoral arteries, respectively. In hepatic, mesenteric and intrarenal arteries, CGRP induced an endothelium‐independent relaxation, whereas either small or no relaxation was obtained in aorta and femoral arteries respectively. A23187 induced an endothelium‐dependent relaxation in the aorta and hepatic artery, whereas A23187 had no relaxant effect in femoral, mesenteric and intrarenal arteries. Nω‐nitro‐l‐arginine (l‐NOARG, 0.3 mM) reduced the maximum ACh‐induced relaxation (in the presence of 10 μM indomethacin) by 66% in the aorta, and abolished the relaxation in femoral and intrarenal arteries. A markedl‐NOARG/indomethacin‐resistant relaxation was obtained in mesenteric and hepatic arteries. Levcromakalim induced a concentration‐dependent and almost complete relaxation in all arteries. When contracted by a 60 mM K+solution, all arteries responded to ACh with a relaxation that was abolished byl‐NOARG. These results demonstrate marked regional differences with regard to the vascular effects of ACh, histamine, CGRP and A23187. Whereas nitric oxide appears to mediate endothelium‐ dependent relaxation regardless of the vascular region, anl‐NOARG/indomethacin‐resistant relaxation, presumably mediated by an endothelium‐derived hyperpolarizing factor, was observed only in mesenteric and hepatic arteries, and aorta.
Septal lesions block sympathetic activation following frontal cortex stimulation in the rat
Authors: MONDA M. , AMARO S. , De LUCA B.
Published: December 2008

The rates of oxygen consumption, colonic and interscapular brown adipose tissue temperature, and discharge of sympathetic nerves innervating the same tissue were recorded before and after orbital frontal cortex stimulation in three groups of rats. These groups consisted of animals with electrolytic lesions of the nucleus medialis septi, with lesions of nucleus lateralis septi or with sham lesions. The values of all the variables considered were similar during the pre‐stimulation time in the three groups of rats. There was an increase in all the parameters in sham‐lesioned animals after electrical stimulation, while no changes were found in the two groups of injured rats. The results showed that the frontal cortex is involved in the control of thermogenesis through the activation of the sympathetic nervous system. Medial and lateral septal nuclei, in spite of their neurochemical and pharmacological differences, share a common role in the pathway from the frontal cortex to the hypothalamic area and the amygdala, which in turn drive the sympathetic nervous system.
Effects of exercise‐training on hypoxia and angiotensin II‐induced pulmonary vasoconstrictions
Authors: KASHIMURA O. , SAKAI A. , YANAGIDAIRA Y.
Published: December 2008

The present study was undertaken to determine whether exercise‐training for 6 weeks would inhibit pulmonary vasoconstriction induced by hypoxia in isolated, blood‐perfused rat lungs. Hypoxic pulmonary vasoconstriction (HPV) and angiotensin II (AH)‐induced pulmonary vasoconstriction were significantly less in the exercise‐trained (ET) group than in the control (cont) group with all challenges. Normoxic pulmonary arterial and capillary pressures in the ET group were significantly lower than those in the cont group and capillary pressor response to hypoxia was less in the ET group than in the cont group. In conclusion, it appears that HPV and AII‐induced vasoconstrictions can be reduced by exercise‐training, because it would seem that exercise‐training repeated responses to increased shear‐stress resulting from elevated blood flow in pulmonary vessels.