bluuebunny/crossref_metadata_2025 huggingface dataset:
Mechanisms of the relaxant and contractile responses to bradykinin in rat duodenum
Authors: WASSDAL  , NICOLAYSEN  , IVERSEN
Published: March 2003

The signal pathway for bradykinin‐induced relaxation followed by contraction in the isolated rat duodenum was investigated by comparing the effect of blocking agents on the response to bradykinin and acetylcholine. The phospholipase C inhibitor U‐73122 inhibited the relaxation induced by bradykinin, but had no effect on the contraction to either bradykinin or acetylcholine. The same response pattern was observed when the tissues were pre‐treated with thapsigargin, a selective inhibitor of microsomal Ca2+ pumps. An inhibitor of non‐voltage‐dependent Ca2+ influx, SK&F 96365, inhibited the relaxant response to bradykinin and the contraction induced by acetylcholine, but not the contraction induced by bradykinin. In Ca2+‐free Krebs–Henseleit buffer, the tissues failed to respond when they were exposed to either bradykinin or acetylcholine. When the tissues were partly depolarized (30 m
M KCl), both bradykinin and acetylcholine induced contraction, while the relaxant response to bradykinin was almost completely abolished. Apamin (an antagonist of low‐conductance calcium‐activated K+ channel) together with charybdotoxin (CTX, an antagonist of large‐conductance calcium‐activated K+ channel) and CTX alone inhibited the relaxant but not the contractile response to bradykinin. We conclude that the biphasic response in isolated rat duodenum to bradykinin involves two distinct pathways. We propose that the relaxant component is induced indirectly via inositol‐mediated increase in cytosolic Ca2+ in non‐muscle cells with subsequent signals to the smooth muscle cells, whereas the contractile response is induced by direct effect on the smooth muscle cells.
Plasma leptin and insulin in C57Bl/6J mice on a high‐fat diet: relation to subsequent changes in body weight
Authors: AHRÉN
Published: March 2003

It has been proposed that leptin and insulin through central effects are involved in the regulation of energy balance and body weight. Whether circulating leptin or insulin levels predict subsequent changes in body weight is, however, not known. We examined plasma leptin and insulin at 2, 3, 6, 9 and 12 months of age in C57Bl/6J mice given a normal diet (n = 12) or a high‐fat diet (58% fat on a caloric base; n = 15). Plasma leptin levels increased by age and correlated with body weight in the entire material (r = 0.81, P < 0.001). Also plasma insulin increased by high‐fat diet and correlated across all age periods with body weight (r = 0.56, P < 0.001). In mice, given normal diet, plasma leptin or insulin did not correlate to subsequent changes in body weight at any of the time points studied. However, in mice given the high‐fat diet, plasma leptin at 6 (r = −0.57, P = 0.027) and 9 months of age (r = −0.56, P = 0.042) as well as plasma insulin at 6 (r = − 0.51, P = 0.049) and 9 months (r = −0.58, P = 0.037) correlated inversely to the change in body weight during the subsequent 3‐month period. Hence, both leptin and insulin are negative predictors for future weight gain in high‐fat fed mice. This suggests that when the regulation of body weight is challenged by a high‐fat diet, leptin and insulin act to restrain or prevent future weight gain. This in turn may suggest that impairment of these (probably central) actions of leptin and insulin might underlie excessive increase in body weight under such conditions.
Involvement of the human splanchnic circulation in pressor response induced by handgrip contraction
Authors: Waaler  , Toska  , Eriksen
Published: March 2003

We have analysed the adjustment of blood flow and vascular conductance in the abundantly supplied splanchnic circulation to a generally released pressor reaction. Pressor responses were induced by 2‐min periods of standardized, sustained handgrip in seven healthy students. The effects of handgrip tests were followed both in the fasting state and after the consumption of a substantial, mixed meal. In the first of the two sessions, changes in superior mesenteric artery blood flow were recorded and concomitant changes in local vascular conductance derived. In the other session, pressor released cardiac output changes were recorded and changes in total peripheral vascular conductance derived. Both types of flow changes were recorded using ultrasound Doppler technique. Typically, blood flow in the superior mesenteric artery increased two‐ to threefold after a meal. Handgrip contractions induced an initial rapid increase in heart rate, cardiac output and total peripheral conductance, followed by a gradual decline in total peripheral conductance and stroke volume and a gradual increase in heart rate and mean arterial pressure for the rest of the period. At the end of 2‐min pressor periods, total peripheral conductance was only about 10% below the pre‐handgrip level, whereas vascular conductance locally in the area of the superior mesenteric artery decreased by some 30%. Thus, it appears that the splanchnic vascular bed contributes markedly to the compound pressor response. Handgrips caused significantly less reduction in local vascular conductance in the post‐prandial than in the pre‐prandial state, indicating that blood flow to the digesting gastrointestinal tract retains a relatively high priority also in a pressor situation.
Regulation of pulmonary nitric oxide by carbon dioxide is intrinsic to the lung
Authors: Adding  , Agvald  , Persson  , Gustafsson
Published: March 2003

Nitric oxide (NO) is present in exhaled air and is a regulator of airways and pulmonary vasculature. Exhaled NO can be depressed by inhaled carbon dioxide (CO2). To further characterize this, single‐breath exhaled NO of rabbits was measured in vivo as well as in buffer‐perfused lungs. Effects of bilateral carotid occlusion or reduction of extracellular pH were also studied. During control conditions NO single‐breath peaks in exhaled air in vivo were 25 ± 1 parts per billion (p.p.b.) as compared with 79 ± 13 p.p.b. in the buffer‐perfused lungs. Inhaled carbon dioxide (FI co2=10%) within 10–20 s caused a depression of exhaled NO in vivo (to 21 ± 1 p.p.b., P < 0.05) and in perfused lungs (to 64 ± 8 p.p.b., P < 0.05). Invivo, the CO2‐induced change in exhaled NO was unaffected by bilateral vagotomy, or by additional guanethidine treatment. Bilateral carotid occlusion did not affect exhaled NO. In perfused lungs, changes in pH (6.5–7.4) did not alter exhaled NO. Endogenous pulmonary nitric oxide production is thus measurable in single breaths in a small animal and is depressed by high airway concentration of carbon dioxide both in vivo and in the perfused rabbit lung. The effect by CO2 is independent of sympathetic outflow and the central nervous system and is not caused by changes in extracellular pH. Carbon dioxide thus exerts a local regulatory effect on lung nitric oxide.
Relationship between skin blood flow and sweating rate in prepubertal boys and young men
Authors: Shibasaki  , Inoue  , Kondo  , Aoki  , Hirata
Published: March 2003

We sought the mechanisms in the maturation‐related change of skin blood flow to heat stress. Eight prepubertal boys (7–11 years) and 11 young men (21–25 years) were exposed to a mild passive heating [by placing the lower legs and feet in a 42 °C water bath for 60 min while sitting in a neutral air condition (25 °C, 45% relative humidity)]. No age‐related differences were observed for the increase in rectal temperature [0.61 ± 0.05 (SEM) vs. 0.62 ± 0.09 °C in the boys and men at the end of the passive heating, respectively], mean skin temperature (34.51 ± 0.28 vs. 34.81 ± 0.27 °C) or metabolic heat production (68 ± 4 vs. 60 ± 3 W m–2) during the passive heating. During the heating age‐related differences in skin blood flow by laser Doppler flowmetry (LDF) and local sweating rate (m˙sw) varied by site; the boys had greater LDF on the chest and back, similar LDF on the forearm and thigh, lower m˙sw on the chest and thigh, similar m˙sw on the back, and greater m˙sw on the forearm, compared with the men. The relationship between LDF and m˙sw during the heat exposure was divided into three temporal phases: (a) an increase of LDF without an increase in m˙sw, (b) an increase of m˙sw without the secondary increase of LDF, (c) a proportional increase of LDF and m˙sw. The increase of LDF in phase (a) and the slopes of the regression lines between the LDF and m˙sw in phase (c) were significantly greater on the chest and back for the boys (P < 0.05), compared with the men, but not on the forearm and thigh. These results suggest that the greater LDF observed on the trunk in the boys may be owing to a greater withdrawal of vasoconstrictor tone and a greater active vasodilation. Regional differences may exist in the maturation‐related alterations in vasoconstriction and vasodilation.
Effects of acute hypobaric hypoxia on regional cerebral blood flow distribution: a Single Photon Emission Computed Tomography study in humans
Authors: Pagani  , Ansjön  , Lind  , Uusijärvi  , Sumen  , Jonsson  , Salmaso  , Jacobsson  , Larsson
Published: March 2003

Single Photon Emission Computed Tomography (SPECT) and radiopharmaceutical stabilizing agents allowed us to investigate regional cerebral blood flow (CBF) distribution in six resting healthy subjects during acute laboratory hypobaric hypoxic conditions. In the hypobaric experiment stabilized 99mTc‐
D,
L‐hexamethyl‐propylene amine oxime was injected 40 min after reaching hypoxic conditions corresponding to an altitude of 5500 m above sea level. Arterial blood sample was taken after five additional minutes. Mean arterial oxygen pressure and haemoglobin saturation were 28 mmHg and 56%, respectively. The control experiment was performed similarly, apart from barometric pressure and blood gas analysis. We analysed CBF distribution in 12 regions of functional interest bilaterally in frontal, parietal, temporal, occipital cortex, in the hippocampus, in the basal ganglia and other central structures of brain. No overall effect of hypoxia on normalized regional CBF distribution in the considered regions was found. Motor cortex (Brodmann 4) and basal ganglia were the only regions in which hypobaric hypoxia significantly increased relative distribution of the radiopharmaceutical [F(1,5)=18.30; P < 0.008 and F(1,5)=10.85; P < 0.022, respectively]. Despite severe hypoxia, we did not observe any major regional CBF redistribution. We found a small relative increase in blood flow to the motor cortex and the basal ganglia, at rest after 40 min of hypobaric hypoxia, suggesting a preferential compensatory mechanism of these functional regions of brain.
Elasticity of tendon structures of the lower limbs in sprinters
Authors: Kubo  , Kanehisa  , Kawakami  , Fukunaga
Published: March 2003

The present study aims to investigate the elasticity of tendon structures of the lower limbs in sprinters and its relation with sprint performance. Subjects were 10 male sprinters and 14 controls whose anthropometric variables and isometric maximum strength were similar. The elongation (L) of the tendon and aponeurosis of vastus lateralis (VL) and medial gastrocnemius muscles (MG) during isometric knee extension and planter flexion, respectively, were determined using a real‐time ultrasonic apparatus in vivo, while the subjects developed a gradually increasing torque from zero (relax) to maximal effort (MVC) within 5 s. While sprinters compared with controls showed significantly greater L above 500 N (about 50% of MVC) and higher dL/dF for VL at less than 20% of MVC during knee extension, there were no significant differences between the two groups in L and dL/dF for MG at every 10% of MVC during plantar flexion. Moreover, the average value of dL/dF above 50% of MVC, proposed as the compliance of tendon structures, did not significantly differ between sprinters and controls in either VL or MG. In a regression analysis within sprinters, the compliance of VL was negatively correlated to 100‐m sprint time, r=−0.757 (P < 0.05), but that of MG was not, r=0.228 (P > 0.05). Thus the present results indicate that the elasticity of tendon structures of VL and MG at high force production levels, which might be assumed to associate with the storage and subsequent release of energy during exercises involving the stretch‐shortening cycle, are similar in both sprinters and controls. For sprinters, however, the tendon structures of VL are more compliant than that for controls at low force production levels, and its elasticity at high force production levels may influence sprint performance.
The effect of α‐phenyl‐tert‐butyl nitrone (PBN) on free radical formation in transient focal ischaemia measured by microdialysis and 3,4‐dihydroxybenzoate formation
Authors: Gidö  , Cronberg  , Wieloch
Published: March 2003

α‐phenyl‐tert–butyl nitrone (PBN) reduces infarct size, improves recovery of brain energy metabolism and delays the secondary increase in extracellular potassium after focal ischaemia, presumably by trapping OH radicals. We investigated the effect of PBN on the formation of 3,4‐dihydroxybenzoic acid (3,4‐DHBA) as a measure of OH radical formation, during and following middle cerebral artery occlusion (MCAO). Rats, subjected to 2 h of ischaemia followed by 3 h of recirculation, were injected with either vehicle or PBN (100 mg kg–1 i.p.) prior to MCAO or immediately after recirculation, respectively. The in vivo microdialysis technique was used to collect samples for analysis of 3,4‐DHBA by HPLC. The basal levels of 3,4‐DHBA were 56–77 nmol L–1 in the four groups. During ischaemia, the formation of 3,4‐DHBA decreased by about 50% in all groups. Upon recirculation, a 3‐fold rise in 3,4‐DHBA formation was seen. At 2 h of recirculation the mean value of 3,4‐DHBA in the pretreated, vehicle‐injected animals was 125 ± 18 nmol L–1 and in the PBN‐injected 145 ± 48 nmol L–1, respectively. When the animals were treated after MCAO either with vehicle or PBN the values at 2 h recirculation were 155 ± 148 and 189 ± 145 nmol L–1, respectively. No statistically significant difference between vehicle‐ and PBN‐injected groups was seen. We conclude that during reperfusion following MCAO, hydroxyl radical formation increases. The increase is not ameliorated by PBN which suggests that PBN does not protect the brain by a general scavenging of OH radicals, although tissue specific actions cannot be excluded.
Further evidence for the existence of a volume‐activated taurine efflux pathway in rat mammary tissue independent from volume‐sensitive Cl– channels
Authors: Shennan  , Thomson
Published: March 2003

The effect of cell‐swelling, induced by a hyposmotic shock, on the fractional loss of taurine, D‐aspartate and iodide from lactating rat mammary tissue explants has been examined. In paired experiments, cell‐swelling markedly increased the fractional efflux of taurine but not that of
D‐aspartate. Similarly, in paired experiments, a hyposmotic challenge stimulated taurine release but not iodide efflux. The results suggest that volume‐activated taurine efflux from mammary tissue explants is via a pathway independent from volume‐sensitive anion channels. It is apparent that the volume‐activated taurine efflux pathway in mammary tissue is not the volume‐sensitive organic osmolyte–anion channel which has been described in other cells. Therefore, the results of this study together with others in the literature constitute prima facie evidence for the existence of more than one type of swelling‐activated pathway which accepts taurine as a substrate.
Adenosine and nitric oxide in exercise‐induced human skeletal muscle vasodilatation
Authors: Rådegran G. , Hellsten Y.
Published: March 2003

The vasoactive substances adenosine and nitric oxide (NO) are credible candidates in the local regulation of skeletal muscle blood flow. Adenosine and NO have both been shown to increase in skeletal muscle cells and interstitial fluid during exercise and the enzymes responsible for their formation, AMP 5′‐nucleotidase and NO synthase (NOS), have been shown to be activated upon muscle contraction. In vitro as well as in vivo evidence suggest that the contraction‐induced increase in interstitial adenosine concentration largely stems from extracellular formation via the membrane‐bound ecto‐form of AMP 5′‐nucleotidase. It remains unclear whether the exercise‐induced NO formation in muscle originates from endothelial NOS in the microvascular endothelium, or from neuronal NOS (nNOS) in nerve cells and muscle fibres. Functional evidence for the role of adenosine in muscle blood flow control stems from studies using adenosine receptor agonists and antagonsits, adenosine deaminase or adenosine uptake inhibitors. The majority of these studies have been performed on laboratory animals and, although the results show some discrepancy, the majority of studies indicate that adenosine does participate in the regulation of muscle blood flow. In humans, evidence is lacking. The role of NO in the regulation of skeletal muscle blood flow has mainly been studied using NOS inhibitors. Despite a large number of studies in this area, the role of NO for the contraction‐induced increase in skeletal muscle blood flow is uncertain. The majority, but not all, human and animal studies show that, whereas blockade of NOS reduces muscle blood flow at rest and in recovery from exercise, there is no effect on the exercise‐induced increase in muscle perfusion. Conclusive evidence for the mechanisms underlying the precise regulation of the multiphased increase in skeletal muscle blood flow during exercise and the role and potency of various vasoactive substances, remain missing.
Diffusive resistance to O2 transport in muscle
Authors: Wagner P. D.
Published: March 2003

Although it has been generally well‐accepted since the work of August Krogh at the start of the 20th century that O2 travels between muscle microvascular red cells and muscle mitochondria by diffusion, the importance of this process to maximal O2 flux remains in question. This review presents data that suggest maximal rates of diffusion of O2 in muscle are limited by both the amount of capillary structure and the haemoglobin concentration in the blood. On the other hand, diffusional conductance appears unrelated to muscle fibre size and thus to distance. Functional data further suggest that the limited rate of diffusion acts to constrain O2 unloading from muscle capillaries and thus also maximal V˙o2, at least in the trained state. In fact, the calculated sensitivity of V˙O2max to muscle diffusional conductance is about as great as that for muscle blood flow. While additional impairment of O2 unloading from perfusion/metabolism heterogeneity cannot yet be excluded (for lack of methodology), it seems evident that the process of O2 transport between the muscle microvasculature and the mitochondria is subject to significant limits, even in health, that have substantial effects on maximal V˙o2.
Lactoferrin and anti‐lactoferrin antibodies: Effects of ironloading of lactoferrin on albumin extravasation in different tissues in rats
Authors: Erga  , Peen  , Tenstad  , Reed
Published: March 2003

Lactoferrin is a cationic iron‐binding protein, which is released from activated neutrophils in concert with reactive oxygen species. In vitro, lactoferrin has both anti‐ and proinflammatory effects; many of them dependent on iron‐binding. In vivo, only iron‐free lactoferrin reduced inflammatory hyperpermeability in the lung. We therefore examined whether 1 mg iron‐free (Apo‐Lf) or iron‐saturated lactoferrin (Holo‐Lf) alone or followed by anti‐lactoferrin antibodies (aLf) affected permeability evaluated by extravasation of radiolabelled bovine serum albumin (CBSA) in different tissues of anaesthetized rats. Fifteen minutes after i.v. injection of Lf, aLf or saline was given and circulatory arrest was induced 20 min thereafter. Measurements were performed in control, after Apo‐Lf, Holo‐Lf, Apo‐Lf + aLf, Holo‐Lf + aLf and aLf alone (n=6–8 in each group). No intergroup differences were found for plasma volume and haematocrit at the start and end of the 37 min extravasation period or for total tissue water in any of the six different tissues studied, excluding larger transcapillary fluid shifts. However, increases in CBSA were seen without differences in tissue intravascular volume. Iron‐free lactoferrin and aLf alone did not change CBSA significantly. Iron‐saturated lactoferrin significantly increased CBSA in skin (neck), trachea and left ventricle of the heart to 249 ± 9, 284 ± 16 and 160 ± 7% of control, respectively. When followed by aLf, both Apo‐ and Holo‐Lf increased CBSA significantly in four and five of the tissues studied, respectively. However, no significant effect was seen for Holo‐Lf + aLf compared with Holo‐Lf alone. In conclusion, iron‐saturated, but not iron‐free lactoferrin increased CBSA, whereas antilactoferrin increased CBSA compared with lactoferrin alone only when following iron‐free lactoferrin.
Hyperbaric oxygen increases parasympathetic activity in professional divers
Authors: Lund  , Kentala  , Scheinin  , Klossner  , Sariola‐Heinonen  , Jalonen
Published: March 2003

The role of autonomic nervous system in hyperoxic bradycardia was evaluated by using the power‐spectral analysis of heart‐rate variability (HRV). Ten professional divers went through two hyperbaric hyperoxic experiments: (1) hyperbaric oxygen (HBO), 100% oxygen at 2.5 ATA, (2) hyperbaric air (HBAIR), O2 21% at 2.5 ATA. Four‐minute traces of ECG were registered and subjected to power‐spectral analysis. Cardiac conduction parameters were evaluated by a diagnostic 12‐lead ECG and arrhythmias by a continuous 3‐lead ECG. Statistical analysis was made using analysis of variance for repeated measurements. Heart rate decreased (P < 0.001), but the response was similar during both treatments (P=0.14). Total power increased significantly more during HBO than HBAIR (P=0.003). High‐frequency (HF) power (P < 0.001), Hayano’s index (P=0.001) and normalized units of HF power (P=0.002) increased and LF/HF index (P < 0.001) decreased more during HBO than HBAIR. There were no changes in cardiac conduction or incidence of arrhythmias. In conclusion, 100% oxygen at 2.5 ATA caused marked increase in parasympathetic tone compared with 21% oxygen at 2.5 ATA.
Muscle training in muscular dystrophies
Authors: Ansved T.
Published: March 2003

There has been a debate for many years on whether muscular training is beneficial or harmful for patients with myopathic disorders and the role of exercise training in the management of these patients is still controversial. Much of this confusion is because of the lack of well‐designed controlled training studies on this heterogenic group of disorders. Because effective therapies are still lacking, the patients have to rely on symptomatic treatment in which continuous physiotherapy plays an important role. There is thus still a need for studies evaluating the short‐ and long‐term effects of muscular training in different types of myopathic disorders. We need to elucidate whether muscular training can increase strength and resistance to fatigue, but most importantly, we need to clarify whether training can improve specific functional abilities of the patient with myopathy. Future studies should give us specific information on what type of training, endurance or strength training, is to be preferred for different myopathies. The effect of strength training in one type of muscle disorder is not directly applicable to another, but is largely dependent on the underlying biological defect. From the studies published so far, high‐resistance strength training at submaximal and possibly also at near‐maximal levels seem beneficial, at least in the short perspective for slowly progressive myopathic disorders. However, the long‐term effects of such training have not been systematically studied. In rapidly progressive myopathies, which are caused by deficient structural proteins such as in Duchenne’s muscular dystrophy, the use of high‐resistance training is far more controversial and questionable. If exercise regimens are to be used, they should preferably commence in the early stages of the disease, at which time there is still a substantial amount of trainable muscle fibres.
Changing dopaminergic activity through different pathways: consequences for renal sodium excretion, regional blood flow and oxygen tension in the rat
Authors: Odlind C. , Fasching A. , Liss P. , Palm F. , Hansell P.
Published: March 2003

Dopamine (DA) is an intrarenal natriuretic hormone involved in sodium homeostasis, but the regulation of renal dopaminergic tonus is unclear. We evaluated different pathways for elevating DA tonus to determine which are important for the ability of the kidney to produce natriuresis and studied the accompanying effects on regional renal blood flow and oxygen tension. Thus, we compared the effects of a catechol‐O‐methyl transferase (COMT)‐inhibitor, an unspecific monoamine oxidase (MAO)‐inhibitor, a D1‐like receptor agonist and a DA precursor in anaesthetized rats. Sodium excretion increased sixfold after COMT inhibition, eightfold after administration of the D1‐like agonist, whereas it was similar to control after MAO inhibition and infusion of DA precursor. Urinary dopamine excretion increased 42% by COMT inhibition, 55% by MAO inhibition and 12‐fold after DA precursor, but remained unchanged after infusion of the D1‐like agonist. The D1‐like receptor agonist led to a 38% increase in the cortical blood flow and a 21% increase in outer medullary blood flow. Regional renal blood flow was unaffected by all other treatments. Cortical and outer medullary oxygen tension was unaffected in all treatment groups. To conclude, the natriuretic and haemodynamic properties of an elevation in DA tonus depends on the route by which the elevation occurred. Systemic administration of a D1‐like receptor agonist, results in a natriuretic response which, as opposed to the natriuresis seen after COMT inhibition, coincides with an increase in renal cortical and outer medullary blood flow. Precursor delivery or MAO inhibition did not change neither urinary sodium excretion nor renal blood flow.
Insulin action on rates of muscle protein synthesis following eccentric, muscle‐damaging contractions
Authors: Fluckey J. D. , Asp S. , Enevoldsen L. H. , Galbo H.
Published: March 2003

The purpose of this study was to determine whether eccentric, muscle‐damaging contractions affect insulin action on muscle protein synthesis. Male Wistar rats (n=28) were anaesthetized either once or twice separated by 7 days’ rest, and one limb was electrically stimulated to contract eccentrically, while the contralateral limb served as a non‐stimulated control. Twenty‐four and 48 h after contractions, rates of protein synthesis were assessed in soleus and red or white gastrocnemius muscles during a hindlimb perfusion with or without insulin (20 000 μU mL–1). Rates of protein synthesis were not different in non‐stimulated muscle, with or without insulin (P > 0.05). In red or white gastrocnemius without insulin, rates of protein synthesis were significantly reduced (P < 0.05) 24 and 48 h after a single session and 48 h after a double session of muscle contractions. However, protein synthesis was normalized with insulin 24 and 48 h after contractions in red, and 48 h after contractions in white gastrocnemius. In soleus muscle, protein synthesis was impaired only 48 h after the second session, but partially restored by insulin (P < 0.05). These results indicate that muscle becomes more sensitive to insulin action on rates of protein synthesis after muscle‐damaging contractions.
Nitric oxide‐induced signalling in rat lacrimal acinar cells
Authors: LOOMS D. K. , TRITSARIS K. , DISSING S.
Published: March 2003

The aim of the present study was to investigate the physiological role of nitric oxide (NO) in mediating secretory processes in rat lacrimal acinar cells. In addition, we wanted to determine whether the acinar cells possess endogenous nitric oxide synthase (NOS) activity by measuring NO production using the fluorescent NO indicator 4,5‐diaminofluorescein (DAF‐2). We initiated investigations by adding NO from an external source by means of the NO‐donor, S‐nitroso‐N‐acetyl‐penicillamine (SNAP). Cellular concentrations of cyclic guanosine 5′‐phosphate (cGMP) ([cGMP]) were measured by radioimmunoassay (RIA), and we found that SNAP induced a fast increase in the [cGMP], amounting to 350% of the [cGMP] in resting cells. Moreover, addition of SNAP and elevating [cGMP] in fura‐2 loaded lacrimal acinar cells, resulted in a cGMP‐dependent protein kinase‐mediated release of Ca2+ from intracellular stores, leading to a rise in the intracellular free Ca2+ concentration ([Ca2+]i). The Mn2+ quenching studies revealed that the Ca2+ release was not accompanied by Ca2+ influx. Finally, we demonstrate that lacrimal acinar cells possess endogenous NOS activity, which is activated by β‐adrenergic stimulation and not by a rise in [Ca2+]i alone.   We show that in rat lacrimal acinar cells, NO and cGMP induce Ca2+ release from intracellular stores via G kinase activation. However, the changes in [Ca2+]i are relatively small, suggesting that this pathway plays a modulatory role in Ca2+ signalling, thus not by itself causing fast transient increases in [Ca2+]i. In addition, we suggest that endogenously produced NO activated by β‐adrenergic receptor stimulation, plays an important role in signalling to the surrounding tissue.
Okadaic acid inhibits relaxant neural transmission in rat gastric fundus in vitro
Authors: STORR M. , FÖLMER R. , KURJAK M. , SCHUSDZIARRA V. , ALLESCHER H. D.
Published: March 2003

The aim of the present study was to characterize the influence of the phosphatase type 1 and 2A inhibitor okadaic acid on non‐adrenergic, non‐cholinergic (NANC) neurotransmission in the rat gastric fundus. Okadaic acid (10−6 M), an inhibitor of protein phosphatases 1 and 2A, did not show any influence on the basal tonus or on a contraction plateau induced by 5‐HT (10−7 M) within 30 min of observation. When okadaic acid (10−6 M) was applied 10 min prior to 5‐HT (10−7 M), the contraction plateau of serotonin was unchanged. To investigate the inhibitory neurotransmission, the muscle strips were pre‐contracted using 5‐HT (10−7 M), and inhibitory stimuli were applied at the contraction plateau, which was stable over 30 min. The inhibitory effects of vasoactive intestinal peptide (VIP), nitric oxide (NO) and electrical field stimulation (EFS, 40 V, 0.5 ms, frequencies ranging from 0.5 to 16 Hz) were examined. When okadaic acid (10−6 M) was applied prior to EFS‐induced NANC relaxation, significant attenuation of the inhibitory response was demonstrated (16 Hz: control: −92.4 ± 1.9%; okadaic acid 10−7 M: –60.7 ± 6.1%; okadaic acid 10−6 M: –25.3 ± 3.4%; n=11; P < 0.01). By contrast, neither the concentration‐dependent inhibitory actions of VIP (10−11–10−8 M) (VIP 10−8 M: –100%; VIP 10−8 M + okadaic acid 10−6 M: –89.9 ± 8.3%; n=8; n.s) nor that of diethylamine nitric oxide (DEA‐NO) (3 × 10−7–10−4 M) (DEA‐NO 10−4 M: –95.3 ± 8.4%; DEA‐NO 10−4 M + okadaic acid 10−7 M: –98.3 ± 6.3%; DEA‐NO 10−4 M + okadaic acid 10−6 M: 96.5 ± 7.6%; n=9; n.s.) on 5‐HT induced contraction were altered by pre‐incubation with okadaic acid (10−6 M). This is the first report that supports the concept that protein phosphatases 1 and 2A may contribute to the regulation of rat gastric fundus motility. The protein phosphatase inhibitor okadaic acid significantly reduces electrically induced inhibitory NANC responses, while leaving direct muscular effects of the inhibitory NANC neurotransmitters VIP and NO unaffected – suggesting a neural site of action. The potential roles of protein phosphatases on NANC neurotransmission remain to be clarified in detail, as this might offer a new pathway for modulating smooth‐muscle function.
Mechanisms of genioglossus responses to inspiratory resistive load in rabbits
Authors: ALEKSANDROVA N. P. , GOLOUBEVA E. V. , ISAEV G. G.
Published: March 2003

The purpose of the present study has been to determine whether pharyngeal dilator muscles participate in inspiratory load compensatory responses and if so, to elucidate role of upper airway mechanoreceptors in these responses. The experiments were performed on anaesthetized rabbits. Each animal was tested in three ways by the imposition of inspiratory resistive load: (1) at upper airways via face mask, (2) at the tracheostomic cannula placed below larynx (all upper airway receptors were `bypassed') and (3) at the mouth after the section of the hypoglossus nerves (motor denervation of genioglossus muscle). The inspiratory load applied to the upper airways evoked significant increases in integrated genioglossus activity (to 129 ± 14.7% of control) and its inspiratory duration (to 113 ± 5% of control) already within the first loaded breath (P < 0.05). The increases in the inspiratory activity of musculius genioglossus were relatively greater than the simultaneous increases in the activity of the diaphragm. Motor denervation of the pharynx dilator muscles (including m. genioglossus) increased airway resistance to 184 ± 19% of control (P < 0.05) and induced obstructive alterations in the breathing pattern during unloaded breathing: decrease in maximal inspiratory flow (–13%) and increase in the level of negative oesophageal pressure (+14%) and the peak diaphragm activity (+6%). After nervi hypoglossus sections additional increases in motor and pressure outputs were required in order to maintain unaltered ventilation at the same degree of loading as before denervation. The results indicate that the pharyngeal dilator muscles have a role in compensation of added inspiratory load. Activation of these muscles facilitate the load compensating function of `pump' muscles by decreasing airway resistance. Tracheostomy did not reduce the genioglossus response to inspiratory loading, ruling out any role for upper airways receptors in the genioglossus response to inspiratory load compensations.
Induction of heme oxygenase in guinea‐pig stomach: roles in contraction and in single muscle cell ionic currents
Authors: Kadinov B. , Itzev D. , Gagov H. , Christova T. , Bolton T. B. , Duridanova D.
Published: March 2003

The role of heme oxygenase reaction products in modulation of stomach fundus excitability was studied. The presence of constitutive heme oxygenase 2 was verified in myenteric ganglia by immunohistochemistry. The role of inducible heme oxygenase isoenzyme was investigated after invivo treatment of animals with CoCl2 (80 mg kg−1 b.w) injected subcutaneously 24 h before they were killed. This treatment resulted in increased production of bilirubin and positive staining for the inducible isoform in stomach smooth muscle and vast induction in the liver. In both control and treated animals haemin, applied to the bath as a substrate of heme oxygenase caused significant decrease of prostaglandin F2α‐induced tone, and ameliorated the relaxatory response of the fundic strips to electrical field stimulation. Both effects were antagonized by Sn‐protoporphyrin IX, competitive heme oxygenase inhibitor, and were found to be neuronally dependent. In single freshly isolated smooth muscle cells from control animals haemin caused a concentration‐dependent increase of the whole cell K+ currents, which was not affected by Sn‐protoporphyrin IX, cyclic guanosine monophosphate (cGMP)‐dependent protein kinase or guanylyl cyclase antagonists, but was reversed by various antioxidants and abolished by an NO scavenger. In cells from treated animals the K+ current increasing effect of haemin did not depend on the presence of antioxidants, but was abolished by protein kinase G and guanylyl cyclase inhibitors, depletors of intracellular Ca2+ pools or Sn‐protoporphyrin IX. Biliverdin did not affect contraction or ionic currents. Thus, this is the first study demonstrating that heme oxygenase is an inducible enzyme in guinea‐pigs, which exerts a modulatory role on gastric smooth muscle excitability via carbon monoxide production.
Exposure of rats to hyperoxia enhances relaxation of isolated aortic rings and reduces infarct size of isolated hearts
Authors: Tähepõld P. , Elfström P. , Eha I. , Kals J. , Taal G. , Talonpoika A. , Valen G. , Vaage J. , Starkopf J.
Published: March 2003

Exposure of rats to hyperoxia before organ harvesting protected their isolated hearts against global ischaemia–reperfusion injury in a previous study. The present study investigates whether hyperoxia influences vasomotor function and regional ischaemia of the heart. Isolated rings of the thoracic aorta were obtained from rats immediately or 24 h after in vivo exposure to 60 min of hyperoxia (>95% O2), and the in vitro dose–response to phenylephrine (PHE), prostaglandin F2α (PGF2α) and endothelin‐1 (ET‐1), acetylcholine (Ach) and sodium nitroprusside (SNP) was assessed. Hyperoxia in vivo increased the relaxation of aortic rings to Ach and SNP, while it delayed contraction to PHE. The effect was more evident when the vessels were harvested immediately rather than 24 h after hyperoxic exposure. In separate experiments rat hearts were isolated immediately after hyperoxia, buffer‐perfused, and subjected to 30 min of regional ischaemia and reperfused for 120 min. Infarct size was determined by triphenyl tetrazolium chloride staining. Hyperoxia significantly reduced infarct size. In normoxic controls 23.0 ± 8.3% of the area at risk was infarcted, while in hyperoxic animals infarct size was 14.8 ± 5.6% of the area at risk (P = 0.012). Exposure of rats to hyperoxia modifies the vasomotor response of isolated aortic rings, and reduces the infarct size of isolated rat heart. These novel aspects of hyperoxic treatment require further studies to explore the potential of its clinical application.
Absorption of biologically active peptide hormones from the small intestine of rat
Authors: Wheeler S. , Mcginn B. J. , Lucas M. L. , Morrison J. D.
Published: March 2003

Absorption of the 4, 10 and 34 amino acid forms of gastrin from the small intestine has been investigated in anaesthetized rats. The method of assessment of successful absorption of the hormone into the systemic circulation was when the amount of acid secreted by the stomach over consecutive 15‐min periods was increased. When the natural hormones were infused into the ileum in a relatively high dose, there was no increase in gastric acid secretion, indicating that they had not been absorbed. Each of the forms of gastrin was conjugated at the free amino terminus to the carboxyl group of cholic acid. Subsequent infusion of the conjugated form of gastrin into the ileum, this time in relatively low doses, resulted in substantial and prolonged increases in gastric acid secretion, indicating that these hormones had been successfully absorbed. In addition, conjugation of the 10 and 34 amino acid forms of gastrin with cholic acid was shown to increase markedly the potency in evoking an increase in gastric acid secretion in response to intravenous injection of the hormone. Absorption of the gastrin conjugates was specific to the ileum thus indicating that they had been absorbed through the bile salt transporters.
Intimal plaque development and oxidative stress in cholesterol‐induced atherosclerosis in New Zealand rabbits
Authors: Heinle H. , Brehme U. , Friedemann G. , Frey J.‐C. , Wolf A. T. , Kelber O. , Weiser D. , Schmahl F. W. , Lang F. , Schneider W.
Published: March 2003

Although oxidative stress is well known in atherogenesis, the origin, nature and kinetics of free radicals involved have not been well described till now. Here, we correlated parameters of oxidative stress with cellular components during induction and stabilization of aortic intimal lesions which were induced in rabbits by feeding a cholesterol‐enriched diet for 6 weeks and a normal diet for further 68 weeks. Plasma lipids, aortic plaque size and composition (macrophages, smooth muscle cells, oxidized LDL by morphometry), as well as aortic radical production (by luminol‐enhanced chemiluminescence and TEMPO‐9AC fluorescence) were measured after various time points. The parameters of oxidative stress were correlated with the different cellular components of the aortic plaques. The plaques increased until week 21, no significant regression was found until week 74, plasma cholesterol was maximal at week 6. Macrophages, oxidized LDL and generation of different species of free radicals were increased during plaque development, yet with different time kinetics. Whereas chemiluminescence correlated only weakly with the amount of intimal macrophages, strong correlations were found between TEMPO fluorescence and smooth muscle cells (r = 0.4778, P < 0.001) and between macrophages and oxidized LDL (r = 0.5896, P < 0.0001). Different indicators of oxidative stress were increased during plaque progression and stabilization. However, the various correlations show, that distinct types of reactive species secreted probably from macrophages and smooth muscle cells contribute to oxidative stress in the different phases of plaque development.
Vasopressin increases milk flow and milk fat concentration in the goat
Authors: Olsson K. , Malmgren C. , Olsson K. K. , Hansson K. , Häggström J.
Published: March 2003

Aim:  The aim of this study was to investigate whether physiological doses of vasopressin affect milk flow and milk composition in goats.

Methods:  Six goats were given vasopressin intravenously at doses of 0.1 ng kg−1 min−1 (a low dose, VL), 0.3 ng kg−1 min−1 (a medium dose, VM) and 1.0 ng kg−1 min−1 (a high dose, VH), oxytocin at 10 ng kg −1min−1 and 0.15 m NaCl during 90 min at random.

Results:  Milk flow increased from 1.3 ± 0.2 to 3.5 ± 1.0 g min−1 (VL), from 1.8 ± 0.4 to 4.3 ± 0.6 g min−1 (VM) and from 1.5 ± 0.2 to 7.9 ± 0.9 g min−1 (VH) during the first 30‐min infusions (all P < 0.001), respectively, and then declined. The response to oxytocin corresponded to that of VH. Milk fat concentration increased from 2.1 ± 0.1 to 3.3 ± 0.4% during VH and from 2.8 ± 0.6 to 4.1 ± 0.6% during oxytocin (both P < 0.001), and tended to increase during VM and VL. The mammary blood flow of four goats was studied with ultrasound during VH and oxytocin infusion. Milk flow increased from 1.8 ± 0.4 to 4.7 ± 1.0 g min−1 during VH and from 1.9 ± 0.3 to 12.4 ± 2.4 g min−1 during oxytocin (both P < 0.001). Mammary blood flow decreased from 262 ± 37 to 53 ± 7 mL min−1 (P < 0.001) during VH, but did not change during oxytocin.

Conclusion:  We conclude that vasopressin increases milk flow and milk fat concentration and suggest that vasopressin, like oxytocin, acts on the myoepithelial cells.
Effects of heat stress on baroreflex function in humans
Authors: Crandall Craig G. , Cui Jian , Wilson Thad E.
Published: March 2003

Introduction: Heat stress significantly reduces orthostatic tolerance in humans. The mechanism(s) causing this response remain unknown. The purpose of this review article is to present data pertaining to the hypothesis that reduced orthostatic tolerance in heat stressed individuals is a result of heat stress induced alterations in baroflex function.

Methods: In both normothermic and heat stressed conditions baroreflex responsiveness was assessed via pharmacological and non‐pharmacological methods. In addition, the effects of heat stress on post‐synaptic vasoconstrictor responsiveness were assessed.

Results: Generally, whole body heating did not alter baroreflex sensitivity defined as the gain of the linear portion of the baroreflex curve around the operating point. However, whole body heating shifted the baroreflex curve to the prevailing (i.e. elevated) heart rate and muscle sympathetic nerve activity. Finally, the heat stress impaired vasoconstrictor responses to exogenous administration of adrenergic agonists.

Conclusion: Current data do not support the hypothesis that reduced orthostatic tolerance associated with heat stress in humans is due to impaired baroreflex responsiveness. This phenomenon may be partially due to the effects of heat stress on reducing vasoconstrictor responsiveness.
Why do human postganglionic neurones primarily only fire once during a sympathetic burst?
Authors: Macefield V. G. , Elam M.
Published: March 2003

Aim:  Single‐unit recordings from muscle vasoconstrictor, cutaneous vasoconstrictor and sudomotor neurones in awake human subjects have shown that they tend to fire only once per sympathetic burst. We review the firing properties of human sympathetic neurones and examine the idea that the short duration of a sympathetic burst may limit the number of times a neurone can fire, using the human skeletomotor system as a model for the sympathetic nervous system.

Results:  It is known that human α motor neurones usually fire in long trains during voluntary contractions, but what of their pattern when constrained by a brief burst? We recorded from single motor units in the tibialis anterior muscle while subjects generated brief electromyogram bursts in the intervals between heart beats, with a duration similar to that of muscle sympathetic bursts. Eight motor units fired mostly one spike per burst, with a pattern identical to that of sympathetic neurones.

Conclusion:  These results suggests that were it not for the constraint of the bursting pattern, individual sympathetic neurones would – like α motor neurones – tend to fire in long trains.
Sympathetic nerve activity in obstructive sleep apnoea
Authors: Narkiewicz K. , Somers V. K.
Published: March 2003

The mechanisms underlying the link between obstructive sleep apnoea (OSA) and cardiovascular disease are not completely established. However, there is increasing evidence that autonomic mechanisms are implicated. A number of studies have consistently shown that patients with OSA have high levels of sympathetic nerve traffic. During sleep, repetitive episodes of hypoxia, hypercapnia and obstructive apnoea act through chemoreceptor reflexes and other mechanisms to increase sympathetic drive. Remarkably, the high sympathetic drive is present even during daytime wakefulness when subjects are breathing normally and no evidence of hypoxia or chemoreflex activation is apparent. Several neural and humoral mechanisms may contribute to maintenance of higher sympathetic activity and blood pressure. These mechanisms include chemoreflex and baroreflex dysfunction, altered cardiovascular variability, vasoconstrictor effects of nocturnal endothelin release and endothelial dysfunction. Long‐term continuous positive airway pressure treatment decreases muscle sympathetic nerve activity in OSA patients. The vast majority of OSA patients remain undiagnosed. Unrecognized OSA may contribute, in part, to the metabolic and cardiovascular derangements that are thought to be linked to obesity, and to the association between obesity and cardiovascular risk. Furthermore, acting through sympathetic neural mechanisms, OSA may contribute to or augment elevated levels of blood pressure in a large proportion of the hypertensive patient population.
A seasonal feast: long‐term analysis of feeding behaviour in the spotted hyaena (Crocuta crocuta)
Authors: Cooper Susan M. , Holekamp Kay E. , Smale Laura
Published: March 2003

The feeding behaviour of the Talek clan of spotted hyaenas in the Masai Mara National Reserve, Kenya, was monitored continuously for 7 years. Talek hyaenas adapted to large temporal variations in prey abundance by being opportunistic predators. During the first half of the year, the hyaenas fed on resident ungulates, and their diet consisted mainly of topi and Thomson's gazelles. Upon arrival of the migratory herds of wildebeest and zebra from the Serengeti, Talek hyaenas switched to feeding on the wildebeest which provided them with a superabundance of food for about 3 months. After the migratory animals returned to the Serengeti, Talek hyaenas experienced a period of reduced prey abundance due to the temporary dispersion of resident ungulates. At this time hyaenas hunted the few remaining wildebeest, and also increased their use of the remaining resident animals. Although Talek hyaenas were generally opportunistic in their feeding behaviour, they did exhibit clear dietary preference for larger prey species, particularly wildebeest. Finally, carrion comprised only 5% of the biomass consumed by Talek hyaenas, the lowest proportion of carrion in the diet of any Crocuta population studied to date.