bluuebunny/crossref_metadata_2025 huggingface dataset:
Post‐tetanic potentiation of the vascular neurogenic response in rats
Authors: SJÖBLOM N. , FOLKOW B.
Published: December 2008

We have previously shown that, at least at frequencies of 4 Hz and above, a previous stimulation of the intramural vasoconstrictor nerves facilitates the subsequent reponse so that even maximal contractions can develop during periods of stimulation as short as a few seconds. In the present study the facilitating effect of a continuous nerve stimulation was quantitatively tested on ‘single‐twitch’ responses to individual nerve impulses. Small arteries and veins (150–500 μm diameter) from rats were mounted in a myograph at known wall tension, and the intramural nerves were activated at frequencies between 0.1 and 32 Hz. After a period of continuous stimulation the single‐twitch responses could be amplified 10–20 times, depending on frequency and duration of the continuous stimulation. No such amplification was observed after application of exogenous noradrenaline. The results therefore reflect a prejunctional frequency‐dependent potentiating mechanism which can strongly reinforce sympathetic neuroeffector control. Furthermore, combined with previous data concerning adrenergic transmitter release, the present results seem to be more compatible with the view that the quantum of transmitter released from each varicosity upon activation is less than an entire granule.
Effect of renal venous pressure elevation on tubular sodium and water reabsorption in the dog kidney
Authors: ABILDGAARD U. , AMTORP O. , HOLSTEIN‐RATHLOU N.‐H. , AGERSKOV K. , SJØNTOFT E. , CHRISTENSEN N. J. , LEYSSAC P. P.
Published: December 2008

This study was performed in order to quantify the effects of renal venous pressure (RVP) elevation on absolute and fractional reabsorption rates of sodium and water in proximal and distal segments of the nephron in dog kidneys. Renal blood flow (RBF) was measured electromagnetically. Clearance of [51Cr]EDTA was used as a measure of the rate of glomerular filtration (GFR). GFR, urinary excretion rates of sodium and water, and lithium clearance were used for assessing the absolute and fractional reabsorption rates of sodium and water in the proximal as well as in more distal segments of the nephron. In the kidneys with intact innervation RVP elevation to 19.9±0.1 mmllg caused significant increases in both absolute (APR) and fractional (FPR) proximal reabsorption rates from 33.4 ± 4.2 to 38.7 ± 2.0 ml min and from 0.62 ± 0.04 to 0.71 ± 0.04, respectively. These responses were unaffected by acute surgical denervation of the kidneys. In contrast, chronic renal denervation or infusion of phentolamine (5 μg kg‐1min‐1) into the renal artery eliminated the increase in APR and FPR during RVP elevation to 20 mmHg. Chronic, but not acute renal denervation depleted renal tissue content of adrenaline and noradrenaline. The results suggest that the increase in APR and FPR during RVP elevation is due mainly to local sympathetic reflex mechanisms.
Haemodynamic characterization of the isolated (denervated) parabiotically perfused rat jejunum
Authors: HAGLUND U. H. , MORRIS J. B. , BULKLEY G. B.
Published: December 2008

The isolated (denervated) parabiotically perfused rat jejunum was characterized for base‐line haemodynamics, autoregulation of blood flow and oxygen consumption and long‐term (3 h) stability with respect to both haemodynamics and the absence of tissue injury. In short‐term experiments, the parabiotically perfused preparation autoregulated oxygen consumption but not blood flow over a wide range of perfusion pressures (25–85 mmHg). When the intestinal segment was subjected to near total ischaemia for 1 h, followed by 1 h of reperfusion, mucosal injury was induced which could be prevented by i.v. administration of superoxide dismutase after ischaemia just prior to reperfusion, or allopurinol prior to ischaemia. These findings support the concept of post‐ischaemic reperfusion injury in the denervated preparation without hepatic ischaemia. This preparation could thus serve as an improved model for the study of the pathophysiology of post‐ischaemic reperfusion injury in the rat intestine.
Temporal relationship of contractility and myocardial potassium balance following beta‐adrenergic stimulation of the in situ pig heart
Authors: ELLINGSEN Ø. , VENGEN Ø. A. , SEJERSTED O. M. , ILEBEKK A.
Published: December 2008

Lower intracellular Na+ during beta‐adrenergic stimulation provides an increased driving force for Na‐Ca exchange, which might attenuate the inotropic response. Since (1) Na+ reduction is coupled to K+ uptake, and (2) K+ uptake lags behind the positive inotropic response to isoproterenol, we could examine the effect of Na‐Ca exchange by comparing cardiac contractility and K+ balance following intracoronary isoproterenol infusion (0.6‐0.8 μg min‐1). In 8 open‐chest pigs, potassium concentrations were continuously measured by PVC‐valinomycin mini‐electrodes in arterial blood (a), and in myocardial venous blood in a shunt from the coronary sinus (cs) to the right atrium. Shunt flow, aortic flow, a left ventricular segment length and left ventricular pressure (LVP) were also continuously recorded. 64 (41–85)% (median and 95% confidence interval) of the LV dP/dt increase occurred within 1 min; thereafter contractility rose slowly. During the first minute of isoproterenol infusion, there was a small net myocardial K+ release, which then reversed to K+ accumulation. A maximum a‐cs K+ concentration difference of 0.20 (0.09‐0.39) mM occurred at 3.0 (2.0–4.25) min, falling to 0.05 (0.01‐0.10) mM after 6.5 (3.75‐8.75) min, at which point accumulated myocardial K+ uptake was 135 (27–219) μmol 100 g‐1. Heart rate remained unchanged and intramural ECG indicated no sign of ischemia during the first 1.5 min of isoproterenol infusion. At 6.25 (5.0–8.0) min after stop of isoproterenol, LV dP/dt was 12 (9–24)% lower than before infusion (P < 0.02) whereas myocardial K+ content remained higher than control. Thus, the monovalent cation shift succeeding the positive inotropic response was not associated with reduced contractility, but could explain the undershoot of LV dP/dt after stopping isoproterenol.
Intracellular pH recovery and lactate efflux in mouse soleus muscles stimulated in vitro: the involvement of sodium/proton exchange and a lactate carrier
Authors: JUEL C.
Published: December 2008

The intracellular pH recovery after stimulation of mouse soleus muscles in vitro was studied by means of intracellular pH‐sensitive microelectrodes. The lactate efflux and the total lactate content were measured by means of an enzymic method. During electrical stimulation for 2 min in a CO2/HCO‐3‐buffered Ringer's solution, pH, decreased by 0.5 units. The rate of pH1‐recovery was independent of external bicarbonate, but dependent on the buffer concentration. The rate of intracellular pH recovery was reduced by the lactate transport inhibitors PCMBS and cinnamate, whereas the inhibitors of inorganic anion‐exchange SITS and DIDS had no effect. The Na+/H+ exchange inhibitor amiloride reduced the rate of pH1, recovery. The pH1 recovery was faster than the lactate efflux, which could be accounted for by an Na+/H+ exchange. A number of inhibitor compounds were used in order to discriminate between the three possible lactate efflux pathways: the monocarboxylate carrier mechanism, the inorganic anion exchange, and the molecular (non‐ionic) diffusion of lactic acid. The lactate efflux was partly inhibited by cinnamate, PCMBS and phloretin, but was unaffected by DIDS and tetrathionate. These experiments demonstrate the existence of a lactate carrier in mammalian skeletal muscles. The lactate carrier is responsible for more than half of the lactate efflux after muscle activity. Both the pH1 recovery studies and the lactate efflux measurements showed that, under the given conditions, the inorganic anion‐exchange mechanism is not essentially involved in the recovery processes after muscle activity.
Morphology of the isolated rat hindquarter preparation: tissue preservation, perfusion heterogeneity and a note on the effect of fixative osmolality
Authors: JOHANSSON B. R. , HARALDSSON B.
Published: December 2008

The isolated rat hindquarter preparation often used for physiological studies was subjected to morphological examination. A two‐hour perfusion with balanced oxygenated dextran solution was followed by perfusion fixation with aldehydes. Fixation was performed at isogravimetry when an isotonic fixative was used (2.5 % glutaraldehyde in 0.05 M Na cacodylate + 4% dextran 70). Muscle specimens were prepared for light and electron microscopy.

Most muscle tissue was well perfused but a limited tissue volume could retain blood after the perfusion period. Within perfused tissue the perfusion result varied macroscopically with some regions apparently not being reached by fixative. Non‐fixed tissue was estimated to amount to maximally one fourth of the total tissue mass. Also within macroscopically well‐fixed tissue the microscopy indicated varying patency of perfused capillaries. Thus a marked perfusion flow heterogeneity prevailed in the fixed specimens which is compatible with earlier functional findings of a 50% reduction of capillary surface area during isogravimetric fixation. The possible relation with prefixation flow heterogeneity in the vasodilated preparation is discussed. There were no obvious alterations of endothelial ultrastructure after prolonged artificial perfusion. Isogravimetrically fixed muscle had narrow extracellular spaces which were evidently compressed further after use of absorbing hyperosmolar fixative. Extracellular expansion and intracellular oedema followed after hypo‐osmolar fixation. Muscle cells often exhibited insufficient mitochondrial fixation, probably as a result of tissue hypoxia.
Dynamics of the interventricular septum and ventricular free walls during regional ischaemia in open‐chest dogs
Authors: GEIRAN O. , MOLAUG M. , ILEBEKK A.
Published: December 2008

The significance of ischaemia of the left ventricular (LV) and right ventricular (RV) free walls for the dynamics of the interventricular septum (IVS) and the right ventricle was examined in open‐chest dogs. Left ventricular and RV ischaemia reduced stroke volume similarly, by 11.2 ± 1.4% and 11 2 ± 2.4%, respectively. The dynamics of myocardial segment lengths (SL), recorded in the LV and RV free walls and the IVS, differed. During LV ischaemia, end‐diastolic SL (EDSL) and systolic shortening (SS) increased in the IVS, whereas SL remained unchanged in the RV free wall. During RV ischaemia, LV EDSL, and SS decreased. Interventricular septum EDSL also decreased, but this reduction was not statistically significant. During blood volume expansion, LV and RV function curves were shifted right, and/or downwards by LV ischaemia, whereas only the RV function curve was shifted downwards and to the right by RV ischaemia. Thus, ischaemia of the LV free wall induces activation of the Frank‐Starling mechanism in the interventricular septum and a deterioration of right ventricular performance.
Intraluminal prostaglandin E2 affects gallbladder function by activation of intramural nerves in the anaesthetized cat
Authors: JIVEGÅRD L. , THUNE A. , SVANVIK J.
Published: December 2008

Gallbladder mucosal net fluid transport and motility were measured in vivo by a continuous perfusion technique in the anaesthetized cat. Prostaglandin E2, administered to the perfused gallbladder lumen, caused a contraction decreasing gallbladder volume capacity, and induced a secretory response by the mucosa. These effects by prostaglandin E2 were abolished by the nerve‐blocking agent tetrodotoxin (administered close intra‐arterially) and somatostatin (administered intravenously), but not by intravenous hexamethonium. Atropine (administered intravenously) reduced the order of magnitude of the gallbladder contraction in response to prostaglandin E2 but did not affect the secretory response by the mucosa. Neither of these drugs significantly affected gallbladder volume capacity or mucosal fluid transport during basal conditions. Tetrodotoxin did not abolish the gallbladder responses to intravenous cholecystokinin or vasoactive intestinal peptide, peptides known to act directly upon smooth muscle and epithelial cell receptors, respectively. It is suggested that prostaglandin E2 affects gallbladder function in vivo mainly by activation of postganglionic non‐cholinergic intramural nerve cells.
Calcitonin gene‐related peptide (CGRP) and transcutaneous electrical nerve stimulation (TENS) increase cutaneous blood flow in a musculocutaneous flap in the rat
Authors: KJARTANSSON J. , LUNDEBERG T. , SAMUELSON U. E. , DALSGAARD C.‐J. , HEDÉN P.
Published: December 2008

The effect of blood flow on transcutaneous electrical nerve stimulation (TENS) and injection of calcitonin gene‐related peptide (CGRP) was studied in a musculocutaneous flap of the rat, using laser Doppler flowmetry. The circulatory border w‐as estimated bcfore and after treatment. It was shown that repeated treatments with TENS gradually increased the blood flow, moving the circulatory border distalll‐ more than 100% after three treatments. Injection of NaCl into the dorsal central vein of the flap resulted in no increase in blood flow, whereas CGRP 10‐10 m increased the blood flow, so that the circulator) border moved distally 70% and 60%, rcspcctivcly.
Differential haemodynamic effects of atrial natriuretic peptide (ANP) in normotensive and spontaneously hypertensive rats
Authors: PETTERSSON A. , RICKSTEN S. E. , HEDNER J. , HEDNER T.
Published: December 2008

Central haemodynamic parameters and cardiac performance were measured in conscious spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto (WKY) control rats after a Io‐min infusion of rat ANP (103–125), I γg kg‐1 min‐1. Mean arterial blood pressure (MAP) decreased by approximately 10% in both groups of rats. Heart rate (HR) increased slightly in both strains during the infusion. In the normotensive group the fall in MAP was due to a reduction in cardiac output (CO) while in the SHR there was a decrease in CO as well as in total peripheral resistance (TPK). The ANP infusion also reduced central blood volume (CRV) and stroke volume (SV) in both groups of rats. The reduction in CRV and CO was significantly more pronounced in the WKY strain. Left ventricular end diastolic pressure (LVEDP) and cardiac contractility (dP/dt) did not change while central venous pressure (CVP) w‐as slightly decreased in the WKY group as a result of the ANP infusion. We conclude that ANP reduces MAP in normotensive animals by a reduction in CO. In the SHR a reduction in TPR also contributes to the fall in MAP. Atrial natriuretic peptide did not exert any negative inotropic effects, but the reduction of CO was due to an increased venous compliance.
Positive inotropic effect on the rat atrial myocardium compressed to 5, 10 and 30 bar
Authors: ASK J. A. , TYSSEBOTK I.
Published: December 2008

The contractile activity of spontaneously beating auricular preparations from the rat was studied during and after pressure exposure to 5, 10 and 30 bar in three series of experiments (compression and decompression rate: I bar min‐1). The preparations were mounted in an organ bath within a pressure chamber and perfused with oxygenated preheated Krebs‐Henseleit solution (37 °C, pH = 7.45) containing α, β‐ and muscarinic‐receptor blockers and blockers of the neuronal and extraneuronal uptake mechanisms. No change in chronotropy of the cardiac preparations were observed during or after exposures to the pressures tested. Significant increase in cardiac contractility (20–40%, P < 0.01) described by the peak tension (Tmax), the maximal velocity of tension rise (T'max) and fall (T'max) were apparent at 5 and 10 bar. Further significant elevations (6–80%, P < 0.05) in T'max, T' and T'min were detected during exposure to 30 bar.

The cardiac contractility increased rapidly with pressure, was approximately unchanged during stable elevated pressures at 5, 10 and 30 bar, but was maintained above control values 15 min after completed decompression. Since no change in chronotropy and loading of the preparations occurred, it is concluded that the increased contractility is due to a positive inotropy generated by the hydrostatic pressure. Furthermore, it is indicated that this positive inotropy is not related to adrenoceptor activation since the effect was achieved in the presence of α, and β‐adrenoceptor blockade.
Gastric mucosal electrical potential difference and blood flow during high FFA/albumin ratios in anaesthetized Göttingen mini‐pigs
Authors: HØJGAARD L. , BÜLOW J. B. , MADSEN J. , CHRISTENSEN N. J.
Published: December 2008

The gastric blood flow and the gastric mucosal potential difference (p.d.) was studied in anaesthetized Göttingen mini‐pigs under normal conditions and during increased FFA/albumin ratios. The antrum mucosal p.d. was measured continuously with a newly developed intragastric microelectrode principle. The gastric blood flow was measured with the radioactive microsphere technique: at basal conditions, during high FFA/albumin ratios, and after normalization of the plasma lipids. The antrum p.d., expressed with gastric lumen negative, decreased during the increased FFA/albumin ratios; from — 25 ± 3 mV to ‐17 ± 4 mV, (P < 0.05). A further reduction to ‐12 ± 3 mV (P < 0.05) was observed during the normalization of the FFA/albumin ratios. The antrum and corpus mucosal blood flow values were reduced by 37 and 26% during the increased FFA/albumin ratios, and the gastric mucosal blood flow returned to initial values after normalization of the plasma lipids. The p.d. reduction during and after the increased FFA/albumin ratios could reflect a reduced active ion transport across the mucosa caused by a changed gastric mucosal metabolism.
Distribution of recurrent inhibition within a motor nucleus. I. Contribution from slow and fast motor units to the excitation of Renshaw cells
Authors: HULTBORN H. , LIPSKI J. , MACKEL R.
Published: December 2008

The relation between the size of a monosynaptic reflex (MSR) to triceps surae and the resulting Renshaw cell discharge was used to evaluate the contribution from slow and fast motor units to the excitation of Renshaw cells. It is, however, difficult to interpret these results in terms of excitation contributed by slow and fast motor units because of the following reasons. First, the size of the MSR recorded in ventral roots is not linearly related to the number of recruited motor units, since larger motor axons contribute more to the size of the MSR than smaller ones. Second, the number of spikes evoked in a Renshaw cell burst is not linearly related to the excitatory input because Renshaw cell discharge saturates in the case of large responses. The contribution of small, early‐recruited motoneurones to Renshaw cell excitation is consequently overestimated. Procedures were introduced to deal with these problems. It is concluded that the last‐recruited motor units (probably ‘fast twitch, fast fatiguing’) on average contribute four times as much excitation to Renshaw cells as the first recruited (‘slow twitch’) motor units.
Hyaluronan in the rat with special reference to the skin
Authors: REED R. K. , LILJA K. , LAURENT T. C.
Published: December 2008

The total hyaluronan content has been determined in rats. The animals were frozen and sectioned in a cryostat before digestion with papain and pronase. The hyaluronan content was determined by a specific radioassay and it was found that 250 g rats contained 40–60 mg of the polysaccharide. The recovery from the preparation procedure was close to 100%, as determined from tracer experiments. More than half of the hyaluronan was found in skin, approximately one quarter in the skeleton and supporting structures and less than one tenth in skeletal muscle. Based on calculated lymph flow and lymph concentration of hyaluronan, it seems that a significant fraction of the total hyaluronan in skin (> 1%) is removed via the lymphatics in a 24 h period. An attempt was made to isolate undegraded hyaluronan from rat skin by gentle methods giving full recovery in order to estimate the molecular weight of the polysaccharide. Hyaluronan was recovered quantitatively, but as determined from added tracer, it had been degraded. Correction for the estimated degradation gave a molecular weight of several millions for the endogenous hyaluronan.
Receptors involved in the nervous system regulation of polyamine metabolism in rat salivary glands
Authors: EKSTRÖM J. , MÅNSSON B. , NILSSON B.‐O. , ROSENGREN E. , TOBIN G.
Published: December 2008

Polyamines are important for protein synthesis and tissue growth. In rat salivary glands, the activity of ornithine decarboxylase (ODC), the enzyme catalysing the formation of putrescine, and the content of putrescine, spermidine, spermine and N1‐acetylspermidine were assayed after parasympathetic or sympathetic nerve stimulation in the presence of various autonomic receptor blockers. Increases in ODC activity occurred on activation of non‐adrenergic and non‐cholinergic receptors in response to parasympathetic nerve stimulation and on activation of α(α1)‐ as well as of β(β1)‐adrenoceptors in response to sympathetic nerve stimulation. Moreover, in parotid glands, a β(β1)‐adrenoceptor‐mediated inverse pathway for putrescine formation seemed to exist: from spermidine via N1‐acetylspermidine.
Effects of neuropeptides and capsaicin on tracheobronchial blood flow of the pig
Authors: MATRAN R. , ALVING K. , MARTLING C.‐R. , LACROIX J.S. , LUNDBERG J.M.
Published: December 2008

Blood flow changes upon systemic i. v.injections in the pig of various neuropeptides, capsaicin, bradykinin and histamine were directly monitored by a Transonic blood flowmeter in the superior laryngeal, bronchial and femoral arteries and indirectly in the larynx and skin using laser Doppler flowmetry. To minimize influence of compensatory reflexes and indirect effects, the pigs were pre‐treated with atropine, guanethidine, chlorisondamine and capsaicin. Substance P (SP), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), calcitonin gene‐related peptide (CGRP), capsaicin, bradykinin and histamine all decreased vascular resistance, suggesting vasodilation in the superior laryngeal and bronchial arteries. All peptides and histamine when given i. v.exerted vasodilatory effects independent of autonomic motor nerves and capsaicin‐sensitive afferents. SP was the most potent vasodilator agent tested in both tracheal and bronchial circulation, being about 1000‐fold more active than histamine. VIP was about 10‐fold more potent than PHI in decreasing vascular resistance and had a preferential action on the SLA compared to CGRP.In the femoral artery capsaicin and also SP in the highest dose increased vascular resistance. Capsaicin increased the laser Doppler signal in both laryngeal mucosa and skin, while i. v.peptides caused variable effects.

In conclusion, SP and CGRP mimicked capsaicin‐induced vasodilation in the tracheobronchial circulation while VIP had a preferential effect on the tracheal circulation.
Autonomic nervous control of cervical secretion in the guinea‐pig
Authors: HAMMARSTRÖM M.
Published: December 2008

Neurogenic influence on cervical secretion was studied in experiments performed on isolated guinea‐pig cervix with intact adjacent nerves. The secretion was estimated as carbohydrate efflux. Experiments were undertaken at ovulation time when secretion is most prominent. Hypogastric nerve stimulation significantly increased carbohydrate release. This response was unaffected by phentolamine but inhibited by TTX, scopolamine and hexamethonium, as well as previous destruction of paracervical ganglia. Pelvic nerve stimulation did not affect cervical secretion. Carbachol as well as VIP induced a secretory response of the same extent as did hypogastric nerve stimulation. Scopolamine abolished the VIP‐induced secretion. VIP and carbachol in combination had no additive effect. It is concluded that cervical glands of the guinea‐pig uterus possess a cholinergic secretomotor innervation. The main pathway is the hypogastric nerve and neurons have a peripheral relay at paracervical ganglia. A more complex peripheral organization cannot be excluded.
Evidence for an intramural nervous control of epithelial cell migration in the small intestine of the rat
Authors: BUSTAMANTE S. A. , FORSHULT M. , LUNDGREN O.
Published: December 2008

The migration of epithelial cells along the crypt‐villus axis in the small intestine of the rat was followed by labelling epithelial cells during mitosis with [3H]thymidine given i.v. Using two different techniques (autoradiography and determination of tissue radioactivity) it was demonstrated that 6–9 h after giving the tracer the labelled cells had migrated longer in intestinal segments exposed to cholera toxin than in control segments. This effect of cholera toxin was abolished by giving hexamethonium. We have earlier shown that cholera toxin induces fluid secretion to a large extent by activating the enteric nervous system and we conclude from the present observations that cholera toxin in a similar fashion exerts a trophic effect on the intestinal epithelium via intramural nervous reflexes. The importance of co‐release of several neurotransmitters in explaining the trophic effect is tentatively discussed.
Factors reducing left and right ventricular output during simultaneous atrioventricular activation in the pig heart
Authors: VENGEN Ø. A. , ELLINGSEN Ø. , ILEBEKK A.
Published: December 2008

Forward stroke volume fell by 26% (23–30%) (median and 95% confidence interval) when simultaneous atrioventricular (Av) pacing was induced at constant heart rate in to anaesthetized open‐chest pigs. To assess the relative importance of factors which could cause this reduction in right and left ventricular (RV and LV) output, we compared cardiac dynamics when either ventricular filling or forward stroke volume was equally reduced by caval constriction and simultaneous AV pacing. We estimated the degree of ventricular filling by recording segment lengths (SL) in the free walls of both ventricles. Our analysis revealed that abolished active LV filling by the left atrium reduced forward stroke volume by 11% (8–14%). The remaining fall in output could be attributed to mitral regurgitation. In the right side of the heart the response was different. The drop in RV filling during simultaneous AV pacing accounted for approximately one‐half of the fall in forward RV stroke volume. Estimates based on SL recordings demonstrated that forward RV stroke volume fell by 7% (2–25%) because of tricuspidal regurgitation. Pulmonary artery pressure was 4.5 (3.4–5.7) mmHg higher during simultaneous AV pacing than during caval constriction, representing a relative rise in afterload that reduced the RV stroke volume by 6–8%. Thus, reduced ventricular filling during simultaneous AV pacing accounted for approximately one‐half of the drop in forward output from both ventricles. Slightly more than one‐half of the reduction in forward LV stroke volume could be attributed to mitral regurgitation. In the right side of the heart tricuspidal regurgitation and a relative rise in pulmonary artery pressure each accounted for about one‐quarter of the fall in forward RV output.
Renal interaction between sympathetic activity and ANP in rats with chronic ischaemic heart failure
Authors: PETTERSSON A. , HEDNER J. , HEDNER T.
Published: December 2008

The diuretic and natriuretic effects of r‐α‐ANP (99–126) were investigated in rats with chronic ischaemic heart failure (IHF) produced by left coronary artery ligation. The plasma concentration of immunoreactive ANP (IrANP) was significantly higher, 91.8 ± 16.0 pm in the IHF rats compared to 31.0 ± 4.9 pm in sham‐operated controls. In the control rats, ANP infusion (0.25–1.0 μg kg‐1 min‐1) increased urine flow rate (V) and urinary sodium (UNaV) excretion. At the highest dose level, both V and UNaV were increased approximately fivefold. The diuresis and natriuresis seen in the control group after the infusion of ANP were blunted in the IHF rats. A bilateral surgical renal denervation in the IHF rats did not alter the renal dopamine levels, but induced a significant decrease in renal noradrenaline content, and almost completely restored the renal responsiveness to the ANP infusions.

We conclude that renal denervation reversed the blunted renal excretory response to ANP in IHF rats. Thus, in experimental IHF, there seems to be a functional antagonism between efferent renal sympathetic nerve activity and ANP.
Effects of growth hormone on skeletal muscle. I. Studies on normal adult rats
Authors: ULLMAN M. , OLDFORS A.
Published: December 2008

A study was made on the effects of recombinant human growth hormone (rhGH) on fast and slow skeletal muscle in normal adult female rats. Daily injections of 4 IE of rhGH over 36 days resulted in increased levels of insulin‐like growth factor I in serum and increased body weight. Morphometric analysis of the muscle fibres of the extensor digitorum longus (EDL) and soleus muscles revealed a significant increase in diameter of both type 1 and type 2 fibres in both muscles. The DNA: protein ratio and the number of satellite cells: muscle fibre in cross‐sections was increased in the GH‐treated rats in relation to controls. The results show that rhGH has pronounced effects on both cell proliferation and muscle fibre growth in skeletal muscle of normal adults rats.
Decreased level of cardiac antioxidants in endurance‐trained rats
Authors: KIHLSTRÖM M. , OJALA J. , SALMINEN A.
Published: December 2008

Han–Wistar rats were exposed to a 194–200 h swimming protocol which caused a significant increase in the cardiac weight. The levels of various tissue antioxidants were assayed from the myocardium of the right ventricle and from the left ventricle (subendoand subepimyocardium). This endurance training decreased the activities of catalase in the right ventricle and in the subendo‐ and subepimyocardium and Cu, Zn‐superoxide dismutase in the subendomyocardium as well as the concentration of vitamin E in the right ventricle and in the subendomyocardium. Also, the activity of thioredoxin reductase decreased in each part of myocardium and that of glutathione reductase in the right ventricle and in the subepimyocardium. The activity of glucose‐6‐phosphate dehydrogenase increased in the right ventricle and in the subepimyocardium. The activity of glutathione peroxidase and the total tissue contents of carnosine and anserine and tissue sulphydryl groups remained unchanged as compared to the control group. The endurance training caused only minor changes in the regional distribution of antioxidants. The major findings were the disappearance of the difference in the activity of catalase between the right and the left ventricle and the increase in the activity of glucose‐6‐phosphate dehydrogenase as compared to that of the left ventricle. The results show that endurance training by swimming decreases the level of cardiac antioxidants. This decrease may be due to the increased oxygen metabolism and the subsequent increase in the formation of oxygen free radicals, which could deplete the antioxidant pool.
Increased survival of ischaemic musculocutaneous flaps in rats after acupuncture
Authors: JANSEN G. , LUNDEBERG T. , SAMUELSON U. E. , THOMAS M.
Published: December 2008

The effects of acupuncture on survival of ischaemic musculocutaneous flaps were investigated in the rat. A dorsal cranially based standard flap (2×7 cm) was elevated and sutured back in position. The percentage survival of the flaps was estimated after 6 days. Manual acupuncture, electro‐acupuncture but not superficial acupuncture significantly increased the survival of the flaps compared to untreated controls. The highest flap survival (92%) was obtained with repeated post‐operative high‐intensity electroacupuncture. It is concluded that acupuncture treatment markedly increases experimental flap survival and may be of clinical importance for treatment of local ischaemia.
Interaction between gastrin‐17 and oxytocin on plasma levels of insulin, glucagon and glucose in conscious dogs
Authors: STOCK S. , UVNÄS‐MOBERG K.
Published: December 2008

The aim of the present study was to investigate how infusion of gastrin‐17 and oxytocin affects plasma levels of insulin, glucagon and glucose in order to elucidate how the two hormones contribute to metabolic changes seen in situations where they are released, e.g. feeding and suckling during lactation. Thus, gastrin‐17 (0.5 and 2.0 nmol kg‐1 h‐1) and oxytocin (0.1 i and 1.1 nmol kg‐1 h‐1) were infused separately or simultaneously into conscious dogs.

Both gastrin‐17 and oxytocin induced significant, dose‐dependent increases in insulin levels. An additive effect on insulin levels was obtained when gastrin‐17 and oxytocin were infused simultaneously. Glucagon levels were not affected by gastrin‐17 whereas infusion of 1.1 nmol kg‐1 h‐1 of oxytocin was followed by a significant increase. In contrast to a slight transient increase in the glucose level induced by oxytocin, infusion of gastrin‐17 caused a sustained period of hypoglycaemia. Thus, infusion of gastrin‐17 and oxytocin, respectively, gave rise to different ratios between circulating concentrations of insulin and glucagon reflected in different effects on the glucose level. The gastrin‐induced hypoglycaemia could reflect that gastrin, via a release of insulin, promotes storing of glucose, e.g. in connection with feeding. That infusion of oxytocin caused a parallel increase in insulin and glucagon levels together with a slight increase in the glucose level could imply that oxytocin favours mobilization of glucose, e.g. during lactation.
Differential effect of bombesin on intraluminal and intravascular release of gastric gastrin and somatostatin in anaesthetized rats
Authors: ALINO S. F. , UVNÄS‐MOBERG K.
Published: December 2008

The aim of the present investigation was to study how bombesin, gastrin‐17, cholecystokinin‐8 (CCK‐8) and electrical vagal stimulation influence the release of gastrin and somatostatin into the gastric lumen. Bombesin (3 and 30 nmol kg‐1 h‐1), gastrin‐17 and CCK‐8 (to nmol kg‐1h‐1) were infused i.v. and vagal stimulations at 5 V, 2 ms, 5 Hz were performed in anaesthetized rats, in which the stomach was perfused with a dextran solution (pH˜ 6 or ˜ 1.5). pH, gastrin and somatostatin levels were measured in the perfusate after having passed the stomach. In addition, blood samples were drawn from the jugular vein in the experiments in which bombesin was infused. Gastrin and somatostatin levels were determined with radioimmunoassay, and gastrin‐ and somatostatin‐like immunoreactivity will be referred to as gastrin and somatostatin below. Infusion of bombesin, 3 and 30 nmol kg‐1 h‐1, did not influence acid secretion as evidenced by an unchanged intraluminal pH. Nor was the intraluminal secretion of gastrin or somatostatin influenced by bombesin, whereas plasma gastrin and somatostatin levels were significantly increased at the higher dose. In contrast, infusion of CCK‐8 and gastrin‐17 (to nmol kg‐1 h‐1), as well as electrical vagal stimulation, significantly decreased the pH and increased the somatostatin levels in the perfusate. Vagal activation in addition increased the gastrin levels.

The present results, demonstrating that bombesin influences plasma and perfusate levels of gastrin and somatostatin differently, indicate that intraluminal and intravascular gastrin and somatostatin release may be separately regulated.
Regional and species differences in vascular reactivity to extracellular potassium
Authors: RYMAN T. , BRANDT L. , ANDERSSON K.‐E. , MELLERGARD P.
Published: December 2008

In‐vitro vasoreactivity to extracellular potassium (Ko+) was tested in isolated human pial and mesenteric arteries as well as basilar and mesenteric arteries from rabbits and rats. Contractions were induced by stepwise increases in [K‐]o and were measured isometrically with a force‐displacement transducer, in small‐volume organ baths. Significant differences between species as well as between regions were found. The threshold of [K+]o for eliciting contraction in human cerebral arteries in hyperosmotic solutions was 10 mM, in rabbit cerebral arteries 17 mM and in rat cerebral arteries 27 mM. The threshold concentration for contraction in mesenteric arteries was significantly higher compared to cerebral arteries in humans and rabbits, but lower in rats: 20 mM in humans, 26 mM in rabbits and 25 mM in rats. In all species the contractile amplitudes were significantly higher in both cerebral and mesenteric arteries when [K+]o was increased under isotonic conditions in the buffer solution than when hyper‐osomolality was created. This difference increased with increasing hyperosmolalitv. In hyperosmotic solutions, the EC50 for [K+]o was lower in cerebral and mesenteric arteries from man than in vessels from rabbit and rat. When the solutions were isotonic, this pattern was seen only in mesenteric arteries. It is concluded that significant species and regional differences in vascular responses to [K+]o exist. Considering that [K+]o is increased in cerebral ischaemia, the observed significantly lower threshold for K+‐induced contractions in human cerebral arteries may be of importance, especially in human cerebral ischaemic events.
Increased cardiac contractility in rats exposed to 5 bar
Authors: STUHR L.E.B. , ASK J. A. , TYSSEBOTN I.
Published: December 2008

The left ventricular pressure, arterial blood pressure and heart rate were studied in three series of pentobarbital‐anaesthetized rats exposed to 5‐bar normoxic (Po2= 0.2 bar) environments: nitrogen‐oxygen (15 and 60 min) and helium‐oxygen (15 min). The maximal left ventricular pressure (LVP max) and the maximal velocities of LVP rise (+ dP/dt max) and fall (‐ dP/dt) were significantly (P < 0.01) increased immediately after reaching normoxic 5 bar (He, 13–28%; N2, 13–23%) and during the exposure at 5 bar (He, 22–44%; N2, 13–18%). The pulse pressure increased significantly (He, 50–62%; N2, 30–34%; P 0.01) during the hyperbaric exposure. No changes in heart rate or end‐diastolic and mean arterial pressure were detected.

The present findings indicate an enhanced cardiac contractility (+ dP/dt max) at 5 bar, with the greatest increase found when He was used as inert gas. The increased contractility was of significant duration (at least 60 min), and was not completely‐reversed until 5–10 min after decompression.
Effects of β‐adrenergic agonists in the parotid gland of the rat–an electrophysiological study
Authors: THESLEFF P.
Published: December 2008

The effects of some β‐adrenergic agonists were studied in the parotid gland of the rat by electrophysiological techniques. In the unoperated gland, isoprenaline caused depolarizations which were slowly developing, long‐lasting and of low amplitude. The same response was seen when noradrenaline was combined with α‐adrenoceptor blocking drugs. A greater number of cells responded to this combination than to isoprenaline.

After either parasympathetic or sympathetic denervation 1–3 weeks in advance, to induce supersensitivity, the number of cells responding to β‐adrenoceptor stimulating drugs was significantly increased. In the latter case the threshold dose required to evoke a response was also significantly lowered. Atropine did not have any effect on the isoprenaline‐evoked response. The combined parasympathetic and sympathetic denervation did not further increase the responsiveness.

It is concluded that β‐adrenoceptor stimulation in the parotid gland of the rat may cause membrane depolarizations. The response is mediated by β1‐ adrenoceptors. The responsiveness is increased in the denervated gland.

Secretory studies have demonstrated a supersensitivity to β‐adrenergic agonists as a result of denervation. On the other hand, β‐adrenoceptor stimulation is believed mainly to activate the adenylate cyclase/cyclic AMP system independent of membrane potential changes. It is thus not known if the present ‘supersensitivity’ is correlated to the increased secretory response earlier demonstrated in this gland.
Regional distribution of citrate synthase and lactate dehydrogenase isoenzymes in the bovine heart
Authors: SYLVÉAN C. , LIN L. , KALLNER A. , JANSSON E.
Published: December 2008

Gradients of oxidative and glycolytic enzyme activities in the heart were studied by comparing samples taken from 10 locations from each of six bull hearts, within 30 min after slaughter. Citrate synthase (CS) was used as a marker of the oxidative potential and the lactate dehydrogenase (LD) subunits H and M as markers of aerobic glycolytic and anaerobic glycolytic potential respectively. CS activity in the ventricular tissue was greater than that of the right atrium, and no difference was found between the right and left ventricles. The left ventricular free wall had higher CS activity at the base than at the apex of the heart. Both the H and M subunit activities of LD increased in the following order: right atrium, right ventricle, ventricular septum, left ventricle. The left ventricular free wall showed higher H and M subunit activities at the base than at the apex. Within the left ventricular wall at the base, subendocardium had higher H and M subunit activities than subepicardium. The M subunit constituted the highest fraction of LD in the subendocardium and in the papillary muscle of the left ventricle. In conclusion, this study suggests that there are metabolic differences along both the radial and the longitudinal axes of the left ventricle and across the ventricular septum. These differences indicate that the greatest cellular stress, both aerobic glycolytic and anaerobic glycolytic in nature, occurs within the subendocardium at the base of the left ventricle and in the left ventricular papillary muscle.
Effects of digitoxin and lithium, used as a marker of passive Na transport, on secretin‐dependent bile flow in the pig
Authors: GROTMOL T. , BUANES T. , RŒDER M.
Published: December 2008

The present study was performed in anaesthetized pigs, and the first aim was to assess the role of Na, K‐ATPase in secretin‐dependent biliary HCO3 secretion (JbHCO3). Intra‐arterial administration of the cardiac glycoside digitoxin (0.2 mg kg1) reduced hepatic NaK‐ATPase activity, JbHCO3 and secretin‐dependent bile flow by 24, 55 and 34% respectively. In the second part of this study lithium (Li) was used as a marker of passive Na transport to assess the electrochemical gradient for Na flux into bile duct lumen during secretin‐stimulated bile flow and impeded biliary osmotic water flow by i.v. infusion of glucose. At plasma glucose 85 (73–96) mmol l‐1, bile [Na] and [Li] exceeded their concentrations in plasma by 57 and 47% respectively. By using the Nernst equation, transepithelial potential difference (PD) during hyperglycaemia was estimated to be –6.2 (0 to –10.8) mV (ductal lumen negative), which corresponds to a [Li]bile/[Li]plasma ratio of 1.3 (1.0–1.5). The ratio was not significantly different from the observed [Li]bile/[Li]p|asma ratio of 1.4(1.3–1.5). It is concluded (1) that Na, K‐ATPase is necessary for JbHCO3, probably by sustaining the cell membrane PD (cell interior negative) which is a driving force for apical electrogenic HCO3 secretion, and (2) transepithelial Li (and hence Na) flux is driven solely by the negative transcellular PD during secretin‐stimulated bile flow in the pig.
Mechanism of action of calcitonin on secretion in rat submandibular gland
Authors: SAGULIN G.‐B. , MÜLLER R. M. , WESTLIND‐DANIELSSON A. , NILSSON T. , BERGGREN P.‐O. , ROOMANS G. M.
Published: December 2008

Calcitonin (CT) was found to reduce the initial flow of pilocarpine‐stimulated saliva from the submandibular glands in the rat. Although there was a concomitant increase of the concentration of calcium and protein in the saliva, the calcium/protein ratio was not significantly affected. CT also caused a significant increase of the potassium concentration in submandibular saliva. Both in vivo and in vitro, CT inhibited the production of cyclic AMP (cAMP) both in the absence and in the presence of forskolin. This decrease in intracellular cAMP levels could result in an inhibition of mucus secretion, which would explain the previously observed calcitonin‐induced intracellular accumulation of mucus in the submandibular gland acinar cells. CT did not affect the cytoplasmic free Ca2+ concentration (as measured with fura 2) in isolated submandibular acini either in the absence or in the presence of cholinergic or adrenergic agonists. These results indicate that the inhibition of fluid secretion in the submandibular gland by calcitonin must be located distal to changes in [Ca2+]i.

It can be concluded that CT affects both mucus and fluid secretion in the submandibular gland, but that only the inhibition of mucus secretion can as yet be explained by an effect at the level of the second messenger.
Effect of sustained exercise on plasma amino acid concentrations and on 5‐hydroxytryptamine metabolism in six different brain regions in the rat
Authors: BLOMSTRAND E. , PERRETT D. , PARRY‐BILLINGS M. , NEWSHOLME E. A.
Published: December 2008

Sustained exercise to fatigue elicits no major differences either in plasma amino acid levels or in brain 5‐hydroxytryptamine (5‐HT) metabolism between sedentary and endurance‐trained animals. Furthermore, 11 weeks of endurance training did not influence the maximal activity of the enzyme monoamine oxidase in the brain areas which were studied. In both sedentary and endurance‐trained rats, sustained running to fatigue caused an increase in the plasma concentration ratio of free tryptophan/other large neutral amino acids and an increase in the concentration of tryptophan in the six brain areas that were studied. The increase was similar in the different regions of the brain and averaged 36%. Exercise caused an increase in the levels of 5‐HT and 5‐hydroxyindoleacetic acid (5‐HIAA) in the brain stem (14 and 44% respectively) and hypothalamus (16 and 17% respectively) and an increase in the level of 5‐HIAA in the hippocampus (21%) and striatum (28%). Exercise also caused an increase in the level of dopamine in the brain stem (56%) and hypothalamus (46%) and of nor adrenaline in the striatum (59%). Since the levels of 5‐HT and dopamine were both increased in the brain stem and hypothalamus, it is possible that these changes may play important roles in the central effects of exercise, including both physical and mental fatigue and effects on mood.
Renal function in different forms of renovascular hypertension in rats
Authors: EKLÖF A.‐C. , APERIA A.
Published: December 2008

This study examines renal function in different rat models of renovascular hypertension. Hypertension was induced by constriction of the aorta proximal to the renal artery (PAC), by PAC and nephrectomy (PAC + Nx) or by renal artery stenosis (RAS). PAC + Nx is equivalent to the Goldblatt 1 kidney‐i clip hypertension model. The PAC rats were studied 3 weeks after surgery. Hypertension was by then well established. GFR, measured as the clearance of inulin, was significantly lower in PAC rats than in control (C) rats. GFR was the same in PAC + Nx rats as in C rats, but significantly lower in PAC + Nx than in Nx rats. Kidney weight was significantly higher in PAC + Nx rats than in C rats. Filtration fraction (FF), measured as the ratio between GFR and the clearance of PAH, was significantly higher in PAC and PAC + Nx rats than in C and Nx rats. In RAS rats hypertension was not established until 6 weeks after surgery, and RAS is equivalent to Goldblatt 2 kidney‐i clip hypertension. Renal artery constriction was moderate as judged from the weight ratio between the stenosed and contralateral kidneys. The GFR in the stenosed kidney was not significantly lower in the contralateral kidney. FF was significantly higher in RAS rats than in C rats in both the stenosed and the contralateral kidneys, but the increase was less pronounced than in PAC and PAC + Nx rats.

Conclusions. An increase in FF is typical of renovascular hypertension. GFR is normal or decreased. In Goldblatt 1 kidney‐i clip hypertension, compensatory hypertrophy blunts the decrease in GFR.