bluuebunny/crossref_metadata_2025 huggingface dataset:
The effects of hexamethonium on cerebral blood flow and cerebral function during relative cerebral ischaemia in rats
Authors: SKARPHEDINSSON J. O. , DELLE M. , CARLSSON S. , BEALER S. L.
Published: October 2003

Cerebral blood flow in either the cortex, thalamic region or the brain stem, as well as somatosensory evoked potentials were measured in a model of moderate cerebral ischaemia in three groups of anaesthetized spontaneously hypertensive rats. The rats were bled to reduce evoked potential amplitudes to ∼50–60% of pre‐haemorrhage control. The consequent blood pressure fall reduced blood flow to ∼65, 80 and 85% of pre‐haemorrhage control in the cortical, thalamic and brain stem regions, respectively, as measured with a laser Doppler flowmeter. Hexamethonium (10 mg kg‐1 i.v.), an autonomic ganglion blocker, caused vasodilation and a slight (7–13 units of prebleeding control) increase in blood flow in all the three regions, and the somatosensory evoked potentials normalized. In addition, the latency of the first evoked potential component decreased toward prebleeding values. Heart rate decreased and a transient decrease was also observed in mean arterial pressure despite an attempt to keep it constant with a pressure regulating reservoir. It is possible that the slightly increased regional cerebral blood flow after hexamethonium injection can explain the improved cerebral function as indicated by the enhanced somatosensory evoked potentials. However, the results might also indicate an autonomic regulation of afferent sensory pathways.
Contractile responses of rat duodenum caused by transmural nerve stimulation: interaction between tachykininergic and cholinergic mechanisms
Authors: TOLESSA T. , LÖDAL M. , HELLSTRÖM P. M.
Published: October 2003

We have studied the importance of tachykinins and acetylcholine for motor stimulation of the rat duodenum in vitro. Contractions induced by transmural nerve stimulation and tachykinin receptor agonists selective for NK1, NK2 and NK3 receptors were used in combination with a neurokinin (NK)2 receptor antagonist, MEN 10,627, and atropine as a muscarinic receptor antagonist. Transmural nerve stimulation in the range 0.5–32 Hz caused frequency‐dependent contractions. MEN 10,627 (10‐8, 10‐7 and 10‐6m) dose‐dependently reduced the contractile frequency–response curve (P<0.01–0.001). Addition of atropine (10‐6m) completely inhibited the response to transmural nerve stimulation (P<0.001). As control, atropine alone reduced this response only by about 65%. Of the tachykinin analogues, [β‐Ala8]‐neurokinin A(4‐10) selective for NK2 receptors caused concentration‐dependent contractions with high potency (pD2 8.01) and high efficacy, while substance P methyl ester acting on NK1 receptors had lower potency (pD2 7.94) and low efficacy, and senktide acting on NK3 receptors had a low potency (pD2 7.52) but high efficacy. With increasing concentrations of MEN 10,627 the response to [β‐Ala8]‐neurokinin A(4‐10) was markedly reduced (P<0.01), while responses to substance P methyl ester and senktide were only slightly affected. Our results indicate that the physiological contractile responses of the rat duodenum are co‐mediated by acetylcholine and tachykinins, for which NK2 receptors seem to be most important.
Inhalation of nasally derived nitric oxide modulates pulmonary function in humans
Authors: LUNDBERG J. O. N. , SETTERGREN G. , GELINDER S. , LUNDBERG J. M. , ALVING K. , WEITZBERG E.
Published: October 2003

The vasodilator gas nitric oxide (NO) is produced in the paranasal sinuses and is excreted continuously into the nasal airways of humans. This NO will normally reach the lungs with inspiration, especially during nasal breathing. We wanted to investigate the possible effects of low‐dose inhalation of NO from the nasal airways on pulmonary function. The effects of nasal and oral breathing on transcutaneous oxygen tension (tcPO2) were studied in healthy subjects. Furthermore, we also investigated whether restoring low‐dose NO inhalation would influence pulmonary vascular resistance index (PVRI) and arterial oxygenation (PaO2) in intubated patients who are deprived of NO produced in the nasal airways. Thus, air derived from the patient's own nose was aspirated and led into the inhalation limb of the ventilator. In six out of eight healthy subjects tcPO2 was 10% higher during periods of nasal breathing when compared with periods of oral breathing. In six out of six long‐term intubated patients PaO2 increased by 18% in response to the addition of nasal air samples. PVRI was reduced by 11% in four of 12 short‐term intubated patients when nasal air was added to the inhaled air. The present study demonstrates that tcPO2 increases during nasal breathing compared with oral breathing in healthy subjects. Furthermore, in intubated patients, who are deprived of self‐inhalation of endogenous NO, PaO2 increases and pulmonary vascular resistance may decrease by adding NO‐containing air, derived from the patient's own nose, to the inspired air. The involvement of self‐inhaled NO in the regulation of pulmonary function may represent a novel physiological principle, namely that of an enzymatically produced airborne messenger. Furthermore, our findings may help to explain one biological role of the human paranasal sinuses.
Middle cerebral artery blood velocity and plasma catecholamines during exercise
Authors: POTT F. , JENSEN K. , HANSEN H. , CHRISTENSEN N. J. , LASSEN N. A. , SECHER N. H.
Published: October 2003

During dynamic exercise, mean blood velocity (Vmean) in the middle cerebral artery (MCA) demonstrates a graded increase to work rate and reflects regional cerebral blood flow. At a high work rate, however, vasoactive levels of plasma catecholamines could mediate vasoconstriction of the MCA and thereby elevate Vmean at a given volume flow. To evaluate transcranial Doppler‐determined Vmean at high plasma catecholamine levels, seven elite cyclists performed a maximal performance test on a bicycle ergometer. Results were compared with those elicited during five incremental exercise bouts and during rhythmic handgrip when plasma catecholamines are low. During rhythmic handgrip the Vmean was elevated by 21±3% (mean±SE), which was not statistically different from that established during moderate cycling. However, at the highest submaximal and maximal work intensities on the bicycle ergometer, Vmean increased by 31±3% and 48±4%, respectively, and this was significantly higher compared to handgrip (P<0.05). During maximal cycling, plasma adrenaline increased from 0.21±0.04 nmol L‐1 at rest to 4.18±1.46 nmol L‐1, and noradrenaline increased from 0.79±0.08 to 12.70±1.79 nmol L‐1. These levels were 12‐ to 16‐fold higher than those during rhythmic handgrip (adrenaline: 0.34±0.03 nmol L‐1; noradrenaline: 0.78±0.05 nmol L‐1). The increase in Vmean during intense ergometer cycling conforms to some middle cerebral artery constriction elicited by plasma catecholamines. Such an influence is unlikely during rhythmic handgrip compared with low intensity cycling.
Peritoneal leucocytes from spontaneously hypertensive rats have reduced chemiluminescence response and lowered sensitivity to dexamethasone in vivo
Authors: SKREDE K. K. , RØSHOL H. , ÆRØ C. E. , WIIK P.
Published: October 2003

The genetically altered hypothalamo‐pituitary‐adrenocortical axis in the spontaneously hypertensive rat (SHR) suggests altered phagocyte function in this strain. We therefore compared luminol‐amplified chemiluminescence in peritoneal leucocytes from 10‐ to 12‐week‐old SHRs and age‐matched Wistar–Kyoto rats (WKYs) activated by serum‐opsonized zymosan particles (SOZ), N‐formyl‐l‐methionyl‐l‐leucyl‐l‐phenylalanine (fMLP) or phorbol 12‐myristate 13‐acetate (PMA). While the number of peritoneal monocytes/macrophages was increased by 49% in SHRs relative to WKYs, activator‐induced chemiluminescence per cell in SHRs was only 14–42% of that in WKYs. FMLP responses were especially low in SHRs. Treatment of rats with dexamethasone in the drinking water for 48 h prior to ex vivo experiments reduced chemiluminescence dose‐dependently in WKYs as well as in SHRs. ED50 of dexamethasone in SHRs was, however, increased compared to WKYs, indicating lowered sensitivity to dexamethasone in SHRs. No evidence was found of strain differences in differential distribution of peritoneal cells or in pharmacokinetics of dexamethasone. Plasma ACTH levels were significantly higher in SHRs than in WKYs, while basal plasma corticosterone concentrations in SHRs and WKYs were not significantly different. The results suggest that production of reactive oxygen compounds by peritoneal mononuclear phagocytes is reduced in SHRs compared with WKYs, and that the phagocyte respiratory burst is modulated differently by endogenous glucocorticoids in the two strains. We propose that reduced activity of the phagocyte NADPH oxidase‐myeloperoxidase system is a major contributory cause of the altered chemiluminescence responses in SHRs. The data indicate that species differences may also be present at earlier steps in the signal transduction pathways activated by SOZ, fMLP and PMA.
An isolated blood‐perfused guinea‐pig lung model for simultaneous registration of haemodynamic, microvascular and respiratory variables
Authors: NYHLÉN K. , RIPPE B. , HULTKVIST‐BENGTSSON U.
Published: October 2003

NYHLÉN, K., RIPPE, B. & HULTKVIST‐BENGTSSON, U. 1997. An isolated blood‐perfused guinea‐pig lung model for simultaneous registration of haemodynamic, microvascular and respiratory variables. Acta Physiol Scand 159, 293–302. Received 13 March 1996, accepted 19 September 1996. ISSN 0001–6772. Department of Preclinical Research, Gambro Lundia AB, Lund, Sweden and Department of Nephrology, University Hospital, Lund, Sweden.

We have developed an optimized isolated lung perfusion system, which possesses several advantages. Firstly, studies of microvascular, respiratory, haematological and biochemical variables are combined in one model. Secondly, blood perfusion resulted in less oedema formation than buffer‐perfused lungs, and high Po2 through ventilation with room air. Finally, data for the variables can be displayed, controlled and recorded in real time using a computerized system permitting subsequent processing (e.g. filtering without destroying original data). In this paper we discuss the basic behaviour of the model in terms of vascular resistance, vascular permeability, respiration and neutrophil sequestration. In addition, the effects of oleic acid, histamine and histamine receptor blockers were tested, and two methods of calculating vascular permeability are discussed. The way in which different anaesthetics affect the neutrophil content of lung tissue and blood was also investigated. In the model, oleic acid increased pulmonary vascular resistance and permeability, whereas histamine did not affect either permeability or the pre/postcapillary vascular resistance ratio. However, histamine receptor blockers increased this ratio, indicating that there was endogenous histamine release. The neutrophil content of the isolated lungs was increased, but this did not affect the variables measured. There was also accumulation of neutrophils in the lungs of blood donor animals, due to CO2 sedation. However, CO2 sedation proved to be superior to pentobarbital or ketamine anaesthesia in maintaining the levels of neutrophils circulating in the blood. In conclusion, this model seems to be sensitive and to yield reproducible results regarding the physiology or pathophysiology of the lung.
Endurance training effects on neurotransmitter release in rat striatum: an in vivo microdialysis study
Authors: MEEUSEN R. , SMOLDERS I. , SARRE S. , DE MEIRLEIR K. , KEIZER H. , SERNEELS M. , EBINGER G. , MICHOTTE Y.
Published: October 2003

MEEUSEN, R., SMOLDERS, I., SARRE, S., DE MEIRLEIR, K., KEIZER, H., SERNEELS, M., EBINGER, G. & MICHOTTE, Y. 1997. Endurance training effects on neurotransmitter release in rat stratium – an in vivo microdialysis study. Acta Physiol Scand159, 335–341. Received 14 May 1996, accepted 15 November 1996. ISSN 0001–6772. Department of Human Physiology and Sports Medicine, Department of Pharmaceutical Chemistry and Drug Analysis, and Department of Neurology, University Hospital, Vrije Universiteit Brussel, Brussels, Belgium; Department of Movement Sciences, Rijksuniversiteit Limburg, Maastricht, the Netherlands.

In the present study we use the in vivo microdialysis sampling technique to register extracellular levels of neurotransmitters in the striatum of trained and untrained rats. We further evaluate the influence of 1 h of exercise on the striatal release of dopamine (DA), noradrenaline (NA), glutamate (GLU) and γ‐aminobutyric acid (GABA) in trained and untrained rats. Male Wistars were randomly assigned to a training or control group. The exercise training consisted of running on a treadmill for 6 weeks, 5 days week−1, with running time and speed gradually increased from 30 min at 19 m min−1 during the first week to 80 min at 26 m min−1 during the final training week. The animals of the control group were placed on the treadmill twice a week, and received a total of four `adaptation sessions', in which they exercised 15–45 min at 26 m min−1. Brain dialysates were analysed with microbore liquid chromatography (LC), with electrochemical detection (monoamines and GABA) and fluorescence detection (GLU). Soleus citrate synthase and basal striatal concentrations of DA, NA and GLU were significantly different between the trained and control animals. Sixty minutes of exercise significantly increased extracellular DA, NA and GLU levels in both groups, but there was no statistically significant difference in the exercise‐induced increase between trained and control animals. There was no statistical difference in basal or exercise‐induced GABA levels between trained and control animals. The results indicate that exercise training appears to result in diminished basal activity of striatal neurotransmitters, while maintaining the necessary sensitivity for responses to acute exercise.
Impaired leucocyte rolling, adhesion and transendothelial migration following cuprophane haemodialysis
Authors: THORLACIUS H. , FERNVIK E. , GAUTAM N. , LUNDAHL J. , RAUD J. , JACOBSON S. H. , LINDBOM L.
Published: October 2003

THORLACIUS, H., FERNVIK, E., GAUTAM, N., LUNDAHL, J., RAUD, J., JACOBSON, S.H. & LINDBOM, L. 1997. Impaired leucocyte rolling, adhesion and transendothelial migration following cuprophane haemodialysis. Acta Physiol Scand 159, 277–283, Received 29 July 1996, accepted 13 November 1996. ISSN 0001–6772. Department of Physiology and Pharmacology, Karolinska Institutet, Stockholm, Sweden.

In this study, we investigated how different steps in the extravasation process of leucocytes, i.e. rolling, adhesion and transendothelial migration, are affected by haemodialysis with cuprophane membranes. Human leucocytes obtained from whole blood prior to clinical haemodialysis and from the afferent blood line (post‐dialyser) 15 min after the initiation of dialysis were injected into the mesenteric microcirculation of urethane anaesthetized rabbits and analysed for their ability to roll in the microvessels by use of intravital fluorescence microscopy. Moreover, neutrophils from the two leucocyte populations were compared with respect to chemoattractant‐induced adhesion and transmigration across confluent monolayers of bovine aortic endothelial cells. Our results show that, as compared with pre‐dialysis leucocytes, 15 min of cuprophane haemodialysis impaired leucocyte rolling by 78 ± 7%, reduced N‐formyl‐methionyl‐leucyl‐phenylalanin (fMLP)‐induced adhesion by 34 ± 9%, and abolished transendothelial migration. These findings demonstrate that intradialytical activation of leucocytes during cuprophane haemodialysis severely affects leucocyte functions that are critical in the extravasation process of these cells at inflammatory tissue sites, and thus may help explain the increased susceptibility to infections observed in patients on chronic haemodialysis.
Adrenalectomy reduces the ability of newborn rats to gasp and survive anoxia
Authors: YUAN S.‐Z. , RUNOLD M. , LAGERCRANTZ H.
Published: October 2003

YUAN, S.‐Z., RUNOLD, M. & LAGERCRANTZ, H. 1997. Adrenalectomy reduces the ability of newborn rats to gasp and survive anoxia. Acta Physiol Scand 159, 285–292. Received 28 March 1996, accepted 8 November 1996. ISSN 0001–6772. Department of Neuroscience, Karolinska Institute; Department of Respiratory and Allergic Diseases, Huddinge University Hospital; Department of Woman and Child Health, Karolinska Hospital, Stockholm, Sweden; Department of Obstetrics and Gynecology, Second Central Hospital, Tianjin, China.

The ventilatory response to anoxia in unanaesthetized rat pups of 1 and 8 days of age was studied. Ventilation was recorded by barometric plethysmography. During acute anoxia (100% N2), animals of both ages responded with hyperpnoea, primary apnoea, hypoxic gasping and secondary apnoea. After secondary gasping, occasional gasps occurred. If oxygen was administered during the gasping period, all animals survived through autoresuscitation. The duration of the period of hypoxic gasping was significantly longer in the 1‐day‐old animals. Adrenalectomy reduced the length of this period in both 1‐ and 8‐day‐old animals. In a second series of experiments, the effect of adrenergic antagonists on autoresuscitation was examined. Pretreatment with the non‐selective α‐receptor antagonist phentolamine reduced the duration of gasping in 1‐day‐old rats, but prolonged this duration in 8‐day‐old rats. The non‐selective β‐receptor antagonist propranolol did not affect the duration of gasping in␣1‐day‐old rats, whereas it prolonged this period in the older animals. We conclude that proper duration of gasping during anoxia is dependent on intact adrenal function and that the adrenal glands therefore play an important role in autoresuscitation from anoxia during postnatal life. The underlying mechanism appears to involve α‐adrenergic receptors.
The energetics of the quiescent heart muscle: high potassium cardioplegic solution and the influence of calcium and hypoxia on the rat heart
Authors: MARQUEZ M.T. , CONSOLINI A. , BONAZZOLA P. , PONCE‐HORNOS J.E.
Published: October 2003

Heart basal metabolism has been classically studied as the energy expenditure of those processes unrelated to mechanical activity and often measured by rendering the heart inactive using cardioplegic solutions (usually by increasing extracellular K concentration ([K]e). In arterially perfused rat heart (at 25 °C), raising [K]e from 7 to 25 mM at a constant extracellular Ca concentration ([Ca]e) (0.5 mM), induced an increase in resting heat production (Hr) from 4.1 ± 0.3 to 5.1 ± 0.3 mol. wt g−1. Under 25 mM K additional increase in [Ca]e further increased Hr to 6.0 ± 0.4, 7.0 ± 0.4 and 8.3 ± 0.9 mol. wt g−1 for 1, 2 and 4 mM Ca, respectively. While under 7 mM K perfusion Hr was not affected by 4 μM verapamil, under 25 mM K and 2 mM Ca 0.4 μM verapamil induced a decrease in Hr (−1.6 ± 0.2 mol. wt g−1, n = 5, P < 0.001). Caffeine increased Hr under 0.5 mM Ca and 7 mM K perfusion (+0.32 ± 0.06 and +1.19 ± 0.25 mol. wt g−1 for 1 and 5 mM caffeine respectively), but under 25 mM K conditions Hr was not affected by caffeine 2 mM. Severe hypoxia decreased Hr under both 7 and 25 mM K (3.7 ± 0.5 to 2.7 ± 0.4 mol. wt g−1 and 7.0 ± 0.4 to 2.2 ± 0.5 mol. wt g−1, respectively) suggesting that the increased Hr associated with the verapamil sensitive fraction of heat released is associated to a mitochondrial mechanism. Therefore, the use of high [K]e overestimates basal values by increasing a verapamil sensitive fraction of the energy released. In addition, high [K]e modifies a caffeine sensitive energy component probably due to a depletion of caffeine‐dependent Ca stores.
Middle cerebral artery blood velocity during rowing
Authors: POTT F. , KNUDSEN L. , NOWAK M. , NIELSEN H. B. , HANEL B. , SECHER N. H.
Published: October 2003

Dynamic exercise increases the transcranial Doppler determined mean blood velocity in basal cerebral arteries corresponding to the cortical representation of the active limb(s) and independent of the concomitant rise in the mean arterial pressure. In 12 rowers we evaluated the middle cerebral artery blood velocity response to ergometer rowing when regulation of the cerebral perfusion is challenged by stroke synchronous fluctuation in arterial pressure. Rowing increased mean cerebral blood velocity (57 ± 3 to 67 ± 5 cm s−1; mean ± SE) and mean arterial (86 ± 6 to 97 ± 6 mmHg) and central venous pressures (0 ± 2 to 8 ± 2 mmHg; P < 0.05). The force on the oar triggered an averaging procedure that demonstrated stroke synchronous sinusoidal oscillations in the cerebral velocity with a 12 ± 2% amplitude upon the average exercise value. During the catch phase of the stroke, the mean velocity increased to a peak of 88 ± 7 cm s−1 and it was in phase with the highest mean arterial pressure (125 ± 14 mmHg), while the central venous pressure was highest after the stroke (20 ± 3 mmHg). The results suggest that during rowing cerebral perfusion is influenced significantly by the rapid fluctuations in the perfusion pressure.
Presence of angiotensin converting enzyme (ACE) activity in serum of amphibian: comparison with ACE activity of mammalian serum
Authors: MIANO A. , BRAMUCCI M. , MURRI O. , QUASSINTI L. , E.  , MACCARI  , ZERANI M. , GOBBETTI A. , AMICI D.
Published: October 2003

The occurrence of angiotensin converting enzyme (EC 3.4.15.1; ACE) was demonstrated for the first time in serum of newt (Triturus carnifex) and frog (Rana esculenta). The enzymatic activity was evidenced following hydrolysis of N‐[3‐(2‐furyl) acryloyl]L‐phenylalanyl glycyl glycine (FAPGG), a synthetic substrate of ACE. The serum enzyme liberated N‐[3‐(2‐furyl) acryloyl]L‐phenylalanine (FAP) from FAPGG. The properties of the amphibian serum enzymes were compared with those of swine. The amphibian serum FAPGG hydrolysing activities were inhibited by typical ACE inhibitors, captopril and lisinopril. The optimum of pH was 8.3 at 10 and 37 °C and the temperature optimum was 45 °C. The values were similar to those of swine serum. The FAPGG Michaelis‐Menten constants (Km) at 37 °C of amphibian serum enzymes (0.337 mm and 0.282 mm for frog and newt, respectively) were lower than that of swine (1.305 mm), but close to human serum enzyme. The Km values obtained at 10 °C were lower than those at 37 °C (0.152, 0.086, and 1.029 mm for frog, newt, and swine serum, respectively). Amphibian sera hydrolysed bullfrog synthetic angiotensin I to produce angiotensin II. Captopril (50 μm) inhibited the production of angiotensin II.
Effects of hydralazine on renal sympathetic nerve activity in normal and congestive heart failure rats
Authors: ZHANG W. , SUN X. , ZHAO X. , THORÉN P. , HEDNER T.
Published: October 2003

We investigated the effects of hydralazine on renal sympathetic nerve activity in anaesthetized heart failure rats. Sham‐operated rats (group 1) received 0.5 mg kg−1 of hydralazine as bolus and were then infused with 0.3–0.5 mg kg−1 h−1 for 3 h intravenously. Heart failure rats received either the same regime (group 2) as group 1, or the same volume of vehicle (group 3). Heart failure rats exhibited lower mean blood pressure (P < 0.05) and elevated renal sympathetic nerve activity (P < 0.01) in the basal state. In group 2, the mean blood pressure decreased 26% after 30 min of hydralazine administration and remained lower for 3 h, with unchanged renal sympathetic nerve activity. In group 1, the mean blood pressure decreased 36%, and the heart rate and renal sympathetic nerve activity were significantly inhibited. Bilateral vagotomy did not alter renal sympathetic nerve response to hydralazine, but resulted in tachycardia. The results indicate that hydralazine, despite its profound hypotensive effect, did not activate renal sympathetic nerve activity in heart failure rats and inhibited renal sympathetic nerve activity in sham‐operated rats. This inhibition was not mediated through the vagal nerve.
Motor unit potential contribution to surface electromyography
Authors: ROELEVELD K. , STEGEMAN D. F. , VINGERHOETS H. M. , OOSTEROM A. VAN
Published: October 2003

The background of the bioelectric activity of muscle recorded from the surface of the skin (surface electromyography) in terms of the representation of single motor units of the underlying muscle(s) is not very well documented or understood. An insight into the composition of an electromyogram is essential for the proper interpretation of one of the most widely applied electrophysiological techniques. In the present paper, a study of the contribution of single motor unit potentials to the surface electromyogram is presented. To this end, the decline of different components of the motor unit potential with depth of the motor unit is quantified. Experimentally, the action potentials from motor units at several positions in the muscle were recorded by 30 skin surface electrodes. Simultaneous use of scanning electromyography provided information about the actual position and size of the motor unit. Observed linear log–log relationships between motor unit potential magnitudes and distance indicated the usefulness of a power function to describe the motor unit potential's dependence on recording distance. It is shown that different specific surface motor unit potential characteristics fall off differently with depth. The magnitude–distance relationship is shown to be dependent on the recording configuration (unipolar vs. bipolar recording, including the inter‐electrode distance) and the chosen motor unit potential parameter (negative peak amplitude, positive peak amplitude and area).
Angiotensin II induces a tachyphylactic calcium response in the rabbit afferent arteriole
Authors: KORNFELD M. , GUTIÉRREZ A. M. , PERSSON A. E. G. , SALOMONSSON M.
Published: October 2003

The influence of repeated administration of angiotensin II (AII) on smooth muscle calcium concentration ([ Ca2+]i) was studied in isolated rabbit renal afferent arterioles loaded with the calcium‐sensitive fluorescent probe Fura–2. [Ca2+]i was evaluated in the proximal and distal parts of the afferent arterioles. AII (10−8m) increased the [Ca2+]i in both these regions. A second administration of AII, however, did not elicit any response in [Ca2+]i. The response to noradrenaline administration at the end of the experiment was not affected, i.e. there was no fading or cross‐desensitization. Since this desensitization was specific for AII, it was of the tachyphylaxis type. Increasing doses of AII (10−11–10−8 m) did not reverse the tachyphylaxis. However, in the proximal part, pretreatment with the voltage‐sensitive calcium channel blocker nifedipine (10−6m) blunted the tachyphylactic effect of a second administration of AII. When l‐arginine (l‐Arg) was administered to the bath solution, thus activating the NO system, the development of tachyphylaxis was suppressed in the proximal region. Pretreatment with the protein kinase C (PKC) inhibitor chelerythrine (10‐6m) did not affect the tachyphylaxis. We conclude that the calcium response to AII in the isolated rabbit afferent arteriole shows tachyphylaxis. This tachyphylaxis cannot be reversed by applying increasing doses of AII (10−11–10−8m). PKC does not seem to be involved in the tachyphylactic phenomenon in this preparation. It was also found that nifedipine and NO reduced the tachyphylaxis.
5‐Hydroxytryptamine, angiotensin and bradykinin transiently increase intracellular calcium concentrations and PKC‐α activity, but do not induce mitogenesis in human vascular smooth muscle cells
Authors: ASSENDER J. W. , IRENIUS E. , FREDHOLM B. B.
Published: October 2003

The potent vasoconstrictor substances, 5‐hydroxytryptamine (5‐HT), angiotensin II (A II), and bradykinin bind to G‐protein coupled receptors and activate phospholipase C‐β. Using the Fura‐2 technique and microfluorometry we found that all three agonists induce a transient increase in intracellular calcium ([Ca2+]i) by releasing stored calcium in human renal artery smooth muscle cells. Using binding of [3H]‐phorbol dibutyrate (PDBu) to quantify membrane‐associated protein kinase C (PKC) we also showed that 5‐HT, A II and bradykinin induced a rapid but transient translocation of protein kinase C (PKC) to the plasma membrane. The time‐course of the rise in [Ca2+]i was similar to that of the increase in [3H]‐PDBu binding, suggesting transient activation of the calcium dependent α‐isoform of PKC. Following prolonged pre‐treatment with tetradecanoyl phorbol acetate (100 nmol L−1), which down‐regulates PKC‐α and δ, the angiotensin‐induced PKC translocation was lost. 5‐HT, A II or bradykinin were unable to increase cell proliferation or act as a co‐mitogens with platelet‐derived growth factor in human vascular smooth muscle cells. Thus, transient increases in [Ca2+]i or PKC activity by a vasoconstrictor agent are insufficient to cause vascular smooth muscle proliferation.
Renal function after myocardial infarction and cardiac arrest in rats: role of ANP‐induced albuminuria?
Authors: NIELSEN S.H. , MAGID E. , SPANNOW J. , CHRISTENSEN S. , LAM H.R. , PETERSEN J.S.
Published: October 2003

Renal function was measured by clearance technique before and after acute myocardial infarction (MI) induced by left coronary artery ligation in male Sprague–Dawley rats. The animals were anaesthetized with halothane‐nitrous oxide, paralysed with pancuronium and artificially ventilated. All parameters were stable throughout the experiment in sham‐operated time control animals (n = 8). After MI, rats developed left ventricular dysfunction with increased left ventricular end‐diastolic pressure and decreased mean arterial pressure. MI produced antidiuresis and antinatriuresis without changes in glomerular filtration rate (GFR), lithium clearance or renal albumin excretion (n = 8). The antidiuretic and antinatriuretic responses to MI were similar in rats with chronic bilateral renal denervation (n = 5). Three additional rats with chronic bilateral renal denervation had cardiac arrest and were resuscitated with cardiac massage, i.v. lidocaine and intracardiac adrenaline administration. These animals showed a transient increase in urine flow rate, sodium and albumin excretion with maximum 30–60 min after resuscitation, while GFR and lithium clearance were normal. Since cardiac ischaemia and sympathetic stimulation are strong stimuli for the release of atrial natriuretic peptide (ANP), we examined if ANP (0.25, 0.50, and 1.00 μg kg−1 min−1, n = 8 per dose) affects urinary albumin excretion. ANP increased dose‐dependently the urine/plasma concentration ratio of albumin relative to inulin, which suggests that ANP increases the glomerular permeability for albumin. We conclude that MI causes stimulation of renal tubular sodium and water reabsorption by a mechanism which is independent of intact renal innervation. MI does not produce any change in renal albumin excretion in rats, but transient albuminuria may be observed in rats following cardiac arrest and/or manoeuvres used in cardiac resuscitation. Since ANP produces albuminuria, we speculate that ANP may be an important mediator of albuminuria in states with elevated plasma concentrations of ANP.
The natriuretic response to a dopamine DA1 agonist requires endogenous activation of dopamine DA2 receptors
Authors: EKLÖF A.‐C.
Published: October 2003

Dopamine produced in the kidney acts as a natriuretic hormone by inhibiting tubular Na+, K+‐ATPase activity. Previous in vitro studies have shown that Na+, K+‐ATPase activity in the proximal tubule is inhibited by a synergistic action of dopamine 1 (DA1) and dopamine 2 (DA2) receptors. This in vivo study, performed on rats, investigates whether the natriuretic response to DA requires a synergistic action of DA1 and DA2 receptors. The DA1 agonist, fenoldopam, significantly increased urinary sodium excretion, but there was no increase in sodium excretion when a DA1 agonist was given together with a DA2 antagonist. Neither DA1 nor DA2 antagonists had any influence on sodium excretion. The natriuretic response to fenoldopam was also significantly attenuated after the administration of benserazide, which inhibits aromatic acid decarboxylase and thereby suppresses the endogenous production of dopamine. In conclusion, the natriuretic effect of dopamine depends on the activation of both DA1 and DA2 receptors. The DA2 receptor appears to be constitutively activated by endogenous dopamine.
The relationships between EMG and muscle morphology throughout sustained static knee extension at two submaximal force levels
Authors: GERDLE B. , KARLSSON S. , CRENSHAW A.G. , FRIDÉN J.
Published: October 2003

This study investigated the relationship between muscle morphology and surface electromyographic parameters (mean frequency, fmean; and signal amplitude, RMS) during sustained static knee extension to exhaustion at 25% maximal voluntary contraction (MVC) and at 70% MVC. Twenty clinically healthy subjects participated. EMGs were registered from the quadriceps. Muscle forces during knee extension at a 90° joint angle were maintained at the respective levels throughout the measurement periods. A biopsy was obtained of the vastus lateralis muscle. The total time to exhaustion was normalized for each subject. By means of regression analysis, the intercept (i ) (i.e. the unfatigued state) and the regression coefficient (k ) were determined for each EMG parameter.

The endurance time increased with decreasing force level. A significantly higher perception of fatigue was found at 25% MVC than at 70% MVC. From principal component analyses it was concluded that RMS‐k at 25% MVC mainly correlated with the type 2 muscle fibre proportions (%), and at 70% MVC mainly with the areas of type 2 muscle fibre. At 25% MVC, fmean‐k correlated with the areas of type 2A, 2B and 2C fibres, and at 70% MVC negatively with the proportion of type 2B and to some extent with areas of type 2A, 2B and 2C fibres. fmean‐i at 25% MVC correlated with fibre type proportions (%); fmean‐i at 70% MVC correlated with the areas of type 2A, 2B and 2C.

The present study indicates relationships between surface EMG and muscle morphology, which is contrary to presented models of the EMG.
Adaptation of myoglobin in compensatory hypertrophied rat muscle
Authors: MASUDA K. , KANO Y. , KATSUTA S.
Published: October 2003

This study investigated the time course change of myoglobin concentration ([Mb]) in skeletal muscle during muscle hypertrophy in rats. Seven groups of Wistar rats (n = 7 per group) were examined. Compensatory hypertrophy of the plantaris muscle was induced by the bilateral ablation of the medial and lateral heads of the gastrocnemius muscle, and the effect of compensatory hypertrophy on the [Mb] of the plantaris muscle was examined at 7, 21 and 42 days post‐ablation. The [Mb] expressed as mg g−1 wet muscle weight tended to decline at 7 days post‐ablation (−12.1%) and returned to the control level by 42 days post‐ablation, as did the muscle protein concentration. However, the [Mb] expressed as mg g−1 protein weight was not significantly different between the ablation and control groups throughout the experimental period. The estimated value of absolute Mb content in the whole plantaris muscle was significantly increased by 28.4% (P < 0.01) at 42 days post‐ablation compared with the age‐matched controls. Therefore, the longer period of compensatory activity allowed the Mb to increase in its absolute content, although the [Mb] did not exceed the level of control muscle. The capacity of facilitated oxygen diffusion and oxygen storage by Mb in the muscle cells will not change even when muscle enlargement takes place.
Effects of calcium channel blockade on intestinal fluid secretion: sites of action
Authors: PEREGRIN A. TIMAR , AHLMAN H. , JODAL M. , LUNDGREN O.
Published: October 2003

Most intestinal secretagogues, including cholera toxin, evoke fluid secretion in part by activating the enteric nervous system (ENS). The enterotoxins that, due to size, cannot pass the intestinal epithelial lining have been proposed to activate the ENS via the release of amines/peptides from the intestinal endocrine cells. It has been shown that calcium channel blockers of the L‐type attenuate intestinal fluid secretion. This study was performed on rat jejunal segments to elucidate where calcium channel antagonists interact with the secretory nervous reflex(es) of the ENS. In vivo, net fluid transport, transmural potential difference (PD) and luminal release of serotonin from the enterochromaffin cells were monitored before and after exposing the intestinal mucosa to cholera toxin (20 μg/mL) or the calcium ionophore A23187 (0.5 mm). In vitro, the effects of transmural electrical field stimulation (EFS) on short circuit current (SCC) was investigated using the Ussing chamber method. Cholera toxin and A23187 evoked a net fluid secretion, an increased PD and an augmented luminal release of 5‐HT. These effects were markedly attenuated by giving the calcium channel blocker nifedipine i.v. (5.75 μmol kg−1 body wt). On the other hand, nifedipine (0.02 mm) had no significant effect on the increased SCC caused by EFS in vitro. The results obtained in the in vivo experiments suggest that the nifedipine markedly attenuates the initial event in cholera toxin‐ and A23187‐induced secretion, the release of amines and probably also of peptides from the intestinal endocrine cells. The in vitro experiments seem to exclude an effect of the calcium channel blockade on the efferent part of the secretory nervous reflex.
Calcium channels and intestinal fluid secretion: an experimental study in vivo in rats
Authors: PEREGRIN A. TIMAR , SVENSSON M. , JODAL M. , LUNDGREN O.
Published: October 2003

Several mechanisms involved in nervous secretory reflex(es) of the enteric nervous system may be dependent on the flux of calcium across the plasma membrane, which may be controlled by voltage‐gated calcium channels. In this study, we investigated the importance of plasma membrane calcium channels for intestinal fluid secretion. Two types of studies were performed, in which intestinal net fluid transport in anaesthetized rats was followed with a gravimetric method. First, the effects on intestinal fluid transport of placing A23187, a calcium ionophore, in the intestinal lumen was studied. A23187 induced in a dose‐dependent manner a net fluid secretion, which was abolished by giving hexamethonium (10 mg kg−1 body wt) i.v. or placing lidocaine (1% solution) on the intestinal serosa. Nifedipine (5.75 μmol kg−1 body wt i.v.) also abolished the fluid secretion caused by the ionophore. In the second study, the effects of various calcium channel blockers (gadolinium chloride, nifedipine, verapamil) were tested on the cholera toxin‐induced secretion. It was attenuated by luminal application of gadolinium chloride (1–10 mm) or nifedipine (10–200 μm). Intravenously administered nifedipine (2.5–5.75 μmol kg−1 body wt) abolished cholera toxin‐evoked secretion dose‐dependently, whereas verapamil (0.05–1 μmol kg−1 body wt) was without consistent effect. It is concluded that the fluid secretion evoked by placing A23187 in the intestinal lumen in vivo was induced via an activation of the enteric nervous system. Cholera secretion was attenuated or abolished by calcium channel blockers of the L‐ or N‐type.
A new improved way of making double‐barrelled ion‐selective micro‐electrodes
Authors: SEMB S.O. , AMUNDSEN B. , SEJERSTED O.M.
Published: October 2003

The methods published for fabrication of double‐barrelled ion‐selective micro‐electrodes are often difficult to follow and give inconsistent results. We describe here a new improved way of making double‐barrelled ion‐selective micro‐electrodes from theta‐style glass capillaries that offers several refinements which improve reproducibility: (1) good control of silanization and (2) dry‐bevelling to assure no inter‐barrel silane contamination and to minimize the signal‐to‐noise ratio by increasing the tip diameter, without compromising the sharpness of the tip.
Duration and mechanisms of the increased natural cytotoxicity seen after chronic voluntary exercise in rats
Authors: JONSDOTTIR I. H. , JOHANSSON C. , ASEA A. , JOHANSSON P. , HELLSTRAND K. , THORÉN P. , HOFFMANN P.
Published: October 2003

We have recently shown that in vivo natural cytotoxicity is enhanced after chronic exercise in spontaneously hypertensive rats (SHRs). In the present report, we have studied the duration of this augmentation and some possible mechanisms involved. Exercise consisted of voluntary running for 4–5 weeks, with the running distance ranging from 2.7–15.6 km day−1 during the last week of running. In vivo cytotoxicity was measured as clearance of injected 51Cr‐labelled YAC‐1 lymphoma cells from the lungs. The in vivo natural cytotoxicity was increased in running SHRs, and also in SHRs that had their running wheel locked for 24 and 48 h prior to the experiment, and was still present after 96 h. The enhancement of in vivo cytotoxicity after 5 weeks of exercise was abolished after an acute injection of the β‐adrenergic receptor antagonist timolol (0.5 mg kg−1 i.v.), indicating that catecholamines are involved in this augmentation. Interestingly, 24 h after the last exercise bout, the increased natural cytotoxicity could be blocked by timolol. The opioid receptor antagonist naloxone given subcutaneously for 7 days by osmotic pumps (6 mg kg−1 h−1) could not reverse the increased in vivo cytotoxicity seen in the running SHRs, suggesting that opioid receptor mechanisms are not involved, or at least not the naloxone‐sensitive μ‐receptor. Natural immunity was not influenced by the histamine H2 receptor antagonist ranitidine, either in controls or in runners, indicating that the natural killer cell‐regulatory effect of histamine is not present in SHRs and does not seem to be involved in the exercise‐induced changes in natural immune function. We conclude that the augmentation of in vivo natural cytotoxicity after voluntary chronic exercise in rats is long‐lasting and that the augmentation is partly mediated by β‐adrenergic receptors.
Attenuation of forearm vasodilator responses to mental stress by regional beta‐blockade, but not by atropine
Authors: LINDQVIST M. , MELCHER A. , HJEMDAHL P.
Published: October 2003

Forearm blood flow during mental stress (Stroop's colour word conflict test) was studied in 18 healthy men before and during regional β‐adrenoceptor blockade (propranolol 0.5 mg), muscarinic receptor blockade (atropine 0.2 mg) and combined blockade, and compared with results obtained in untreated controls. Forearm blood flow was measured with venous occlusion plethysmography, and forearm vascular resistance was calculated. Arterial and venous blood sampling was performed for determination of adrenaline and noradrenaline in plasma. Mental stress increased heart rate, systolic and diastolic blood pressures and forearm blood flow, and lowered the forearm vascular resistance, to the same degree as in our previously studied controls. Neither of the intra‐arterially administered drugs had any discernible systemic effects. Beta‐blockade increased forearm vascular resistance by 32% and decreased forearm blood flow by 21% compared with unblocked levels during mental stress, whereas forearm vasodilation was maintained throughout the stress test in the control group (P < 0.05). Intra‐arterial atropine had no certain effects. Arterial adrenaline levels during mental stress were similar in the receptor‐blocked and control groups. In conclusion, the sustained forearm vasodilation during mental stress appears to be partly mediated via β2‐adrenoceptor stimulation (i.e. by adrenaline), but we obtained no support for a cholinergic vasodilating mechanism.
Myosin heavy chain composition of regenerated soleus muscles during hindlimb suspension
Authors: BIGARD A.X. , SERRURIER B. , MERINO D. , LIENHARD F. , BERTHELOT M. , GUEZENNEC C.Y.
Published: October 2003

The aim of this study was to determine the MHC profile of regenerated soleus muscles in control (C, n = 8) and hindlimb suspended rats (HS, n = 8). After muscle degeneration was induced by injection of snake venom containing notexin, male rats were either tail suspended for 21 days or submitted to normal weight‐bearing activity. Separation and detection of MHCs by sodium dodecyl sulphate–polyarcylamide gel electrophoresis (SDS–PAGE) showed that regenerated soleus muscles from C rats contained only type I and type IIa MHCs. The relative amount of type I MHC was higher in regenerated (93.9 ± 1.7%) than in untreated muscles (86.5 ± 2.3%) (P < 0.01). In the HS group, the immunohistochemical analysis showed that the majority of regenerated myofibres reacted positively with the antibody against fast MHCs. SDS–PAGE analysis demonstrated that HS resulted in a shift toward faster MHCs in both intact and regenerated myofibres. Regenerated soleus muscle from HS rats contained ≈34% type IIa MHC, ≈37% type IIx/d MHC and ≈18% type IIb MHC, when type I MHC contributed to only ≈12% of total myosin. The proportions of fast MHC isoforms in regenerated muscles were higher than those recorded in untreated muscles. Collectively, these results suggest that the shift in the MHC profile associated with hindlimb unweighting in adult undamaged soleus muscles is also related to the heterogeneity of early myoblasts.
Intracoronary blockade of angiotensin‐converting enzyme in humans: Interaction with cardiac sympathetic neurotransmission?
Authors: RUNDQVIST B. , EISENHOFER G. , EMANUELSSON H. , ALBERTSSON P. , FRIBERG P.
Published: October 2003

The present study was designed to identify an interaction between the renin–angiotensin system and noradrenergic transmission in the human heart. It is still under debate whether angiotensin II facilitates noradrenaline release in the heart. Clinical studies of congestive heart failure, involving systemic angiotensin‐converting enzyme (ACE) inhibitor administration, have indicated anti‐adrenergic effects, without giving a clear mechanistic picture. The influence on cardiac sympathetic transmission by local intracardiac administration of an ACE inhibitor has not been determined. Seven angina patients with normal left ventricular function, who underwent control coronary angiography after successful percutaneous transluminal coronary angioplasty were studied. Baseline measurements of haemodynamics and total and cardiac noradrenaline spillover were followed by handgrip exercise in the absence and presence of intracoronary enalaprilat infusion (0.05 mg min−1, 1 mL min−1). Baseline total body and cardiac noradrenaline spillover remained unchanged following intracoronary enalaprilat infusion, being 3745 ± 349 and 3896 ± 257 pmol min−1, and 148 ± 56 and 149 ± 55 pmol min−1, before and after drug administration, respectively. Mean arterial pressure, peripheral plasma renin activity and angiotensin II levels were also unaffected by enalaprilat infusion. During handgrip exercise procedures, both total body and cardiac noradrenaline spillover increased substantially, showing no reduction in the presence of intracardiac enalaprilat.

Direct administration of the ACE inhibitor enalaprilat to the human heart failed to attenuate cardiac sympathetic drive during baseline conditions or following cardiac adrenergic activation by handgrip exercise. Thus, in the non‐failing heart, without chronic adrenergic activation, no angiotensin II‐facilitated effect on cardiac noradrenaline spillover could be detected.