bluuebunny/crossref_metadata_2025 huggingface dataset:
Ischaemia‐induced injury in glycogen‐depleted skeletal muscle. Selective vulnerability of FG‐fibres
Authors: JENNISCHE EVA
Published: December 2008

JENNISCHE, E. 1985. Ischaemia‐induced injury in glycogen‐depleted skeletal muscle. Selective vulnerability of FG‐fibres. Acta Physiol Scand, 125,727–734. Received 16 April 1985, accepted 20 July 1985. ISSN 0001–6772. Department of Histology, University of Göteborg, Sweden.

The effect of preischaemic glycogen‐depletion on the development of skeletal muscle injury was investigated in rats subjected to tourniquet hind‐limb ischaemia. Glycogen depletion was performed by direct electrical stimulation of the extensor digitorum longus (EDL) muscle during ischaemic conditions. The metabolite load during the subsequent 2.5 h of ischaemia was modified by allowing, or not allowing, a short reperfusion period after termination of the electrical stimulation. The extent of injury was evaluated morphologically after 5 or 15 h of reperfusion, by the combination of an intravital dye exclusion test and a histochemical staining, demonstrating calcium‐precipitates‐Alizarin red S. Minimal damage was found in animals subjected to ischaemia without preceding glycogen depletion. In both groups of preischaemically glycogen‐depleted animals, significant irreversible injury occurred. The injury was significantly less in animals in which a wash‐out period was allowed after termination of stimulation. Fast‐glycogenolytic fibres (FG) were most sensitive to the ischaemic insult during both experimental conditions, while slow‐oxidative fibres (SO) were spared. Fast‐oxidative‐glycogenolytic fibres (FOG) showed an intermediate response. The injury seemed to be established after 5 h of reperfusion, indicating that cells react with an all‐or‐nothing response in the present model.
Effects of a‐adrenoceptor subtype‐selective antagonists on the human saphenous vein in vivo
Authors: STEEN STIG , CASTENFORS JAN , SJÖBERG TRYGVE , SKÄRBY TOR , ANDERSSONJ KARL‐ERIK , NORGREN LARS
Published: December 2008

The effects of the α‐adrenoceptor subtype‐selective antagonists prazosin (α1) and yohimbine (α2) on the saphenous vein of six healthy male subjects were investigated in vivo. The drugs were infused locally into the congested (40 mmHg), long saphenous vein constricted by simultaneous local infusion of noradrenaline (NA). Prazosin 10‐9 M (concentration in the infusion solution, infusion rate 0.3 ml min_I) did not reduce the NA‐induced venoconstriction, but at a concentration of 10‐8 M there was a significant reduction; in two subjects no response to NA could be elicited in the presence of 10‐8 M prazosin. Prazosin 10‐7 M caused no further reduction of the NA effect compared to that produced by 10‐8 M in three of the subjects, whereas in one, prazosin 10‐9, 10‐8 and 10‐7 M caused a dose‐dependent blockade. Yohimbine, 10‐9, 10‐8 and 10‐7 M caused a dose‐dependent reduction of the NA‐induced venoconstriction in all subjects. The results suggest that the human saphenous vein is endowed with functionally important populations of both α2‐ and a1‐adrenoceptors.
Release of substance‐P‐like immunoreactivity in dog paw lymph after scalding injury
Authors: JONSSON CARL‐EVERT , BRODIN ERNST , DALSGAARD CARL‐JOHAN , HAEGERSTRAND ANDERS
Published: December 2008

The level of substance‐P‐like immunoreactivity (SPLI) in dog paw lymph was determined before and after scalding injury of the paw. At basal conditions, no SPLI could be detected in the paw lymph. Scalding induced an immediate increase of the SPLI‐levels. Within 5–10 min after the scalding injury the levels increased up to 28 fmol ml‐1and then gradually decreased within 30–90 min after the injury. It is suggested that scalding injury results in release of substance P from sensory nerve endings, and that this release may contribute to the inflammatory response to scalding injury and, possibly, also wound healing.
Complementary action of substance P and vasoactive intestinal peptide on the rat parotid secretion
Authors: EKSTRÖM JÖRGEN , OLGART LEIF
Published: December 2008

Augmentation of the rat parotid salivary secretion to intravenous injections of substance P (SP) occurred when SP was combined with vasoactive intestinal peptide (VIP), or stimulation of the auriculotemporal nerve in the presence of atropine and the adrenergic blockers, dihydroergotamine and propranolol. The largest increase was obtained when SP (0.5 μg kg‐1) was used together with subthreshold doses of VIP (84% at 0.05 μg kg‐1 and 105% at 0.5 μg kg‐1) and low frequency stimulation (92% at 2 Hz and 97% at 5 Hz), which did not produce any salivary secretion by itself. There was no facilitated secretion when VIP and nerve stimulation were combined. Amylase output was much larger (250–500%) when SP was combined with nerve stimulation (0.5‐5 Hz) or VIP (0.005‐5 μg kg‐1) than when SP was used alone. Similar results were obtained in rats where the auriculo‐temporal nerve was stimulated during the early phase (24–90 h) of Wallerian degeneration, when the nerve‐induced responses were seemingly completely blocked. Our results are consistent with the hypothesis that both VIP and SP contribute to the atropine‐resistant parotid secretion, and that they have a complementary role in the rat parotid exocrine function.
Histochemical and metabolic characteristics of human skeletal muscle in relation to age
Authors: ESSÉN‐GUSTAVSSON B. , BORGES O.
Published: December 2008

Muscle fibre composition, fibre areas and enzyme activities were determined in muscle biopsy samples (m. vastus lateralis) from both legs of 34 clinically healthy men and 31 clinically healthy women (aged 20–70 years). No significant difference was found in any of the three variables between the right and left leg. In the whole material the mean percentage of type I fibres was significantly higher in men, whereas that of type IIA fibres was significantly higher in women (men 58% I, 27% IIA, 13% IIB, women 51% I, 32% IIA, 15% IIB). The areas of all fibre types were significantly larger in men than in women. When the subjects were divided into age groups of 20, 30, 40, 50, 60 and 70 years, respectively, the fibre composition was found to be similar at different ages in both men and women, but changes in fibre areas were observed. The 70‐year‐old men and women showed significantly reduced areas of both type I and II fibres compared with the 60‐year‐olds. Only minor changes were seen in enzyme activities in relation to age. Men of the youngest age group had significantly higher levels of citrate synthase activity than those of the older age groups. Similar findings were seen for women except for the 60‐year‐olds, who had as high activity levels of citrate synthase as the 20‐year‐olds.
Dopamine release is enhanced while acetylcholine release is inhibited by nimodipine (Bay e 9736)
Authors: NORDSTRÖM ÖIE , BRAESCH‐ANDERSEN STEN , BARTFAI TAMAS
Published: December 2008

The calcium‐channel ligand, nimodipine (Bay e 9736), in submicromolar concentrations (10‐7 to 10‐5 M), enhanced the potassium (25 mM) or electrical stimulation (1 Hz, 1 ms, 180 pulses) evoked release or [3H]dopamine from rat striatal slices, while it inhibited the release of [3H]acetylcholine. Nimodipine had similar effects on slices from the cerebral cortex loaded with [3H]dopamine or [3H]acetylcholine, the electrical stimulation evoked release of the catecholamine was enhanced, while release of f3H]acetylcholine was suppressed. The data indicate that nimodipine may distinguish between Ca2+channels in dopaminergic and cholinergic nerve‐terminals. The simultaneous elevation of dopamine release and suppression of acetylcholine release may prove useful in the treatment of Parkinson's disease.
Adrenergic innervation and neurogenic response in large and small arteries and veins from the rat
Authors: NILSSON HOLGER , GOLDSTEINJ MENEK , NILSSON OLA
Published: December 2008

A combined morphological and physiological analysis of the properties of the adrenergic vasoconstrictor innervation was carried out in the splanchnic vasculature in the rat. Three generations of vessels were studied: (1) the abdominal aorta and the caval vein; (2) the superior mesenteric artery and vein; (3) 200 μm branches of the superior mesenteric artery and their parallelling veins. The adrenergic innervation was visualized by the Hillarp‐Falck fluorescence technique, and by the immunohistochemical localization of immunoreactivity to tyrosine hydroxylase and dopamine‐β‐hydroxylase. Determination of responses to applied noradrenaline, to transmural nerve stimulation and to direct activation of the muscle was made on ring preparations mounted in a myograph. All vessels were found to be innervated at the adventitio‐medial border by noradrenergic nerves with varying density; the small arteries had the highest nerve density, the abdominal aorta was least innervated. When related to the maximal isometric response to applied noradrenaline, the maximal neurogenic response parallelled the density of the adrenergic innervation. Variations in frequency for half‐maximal response among the vessels could not, however, be ascribed to innervation properties only. The constriction under isotonic conditions amounted to 20% of the initial circumference in the aorta, and to 30% in the small arteries and veins. The relation between response to applied noradrenaline and to nerve stimulation was similar for isometric and isotonic responses. In the smaller veins, a β‐receptor‐mediated decline in the response to applied noradrenaline was seen. This decline was much less pronounced in neurogenic responses. The results indicate a gradation from proximal to peripheral arteries towards denser innervation and greater neurogenic responses. On the venous side only minor differences were found.
Electrophysiological properties of calcitonin‐secreting cells derived from human medullary thyroid carcinoma
Authors: SAND O. , JONSSON L. , NIELSEN M. , HOLM R. , GAUTVIK K. M.
Published: December 2008

Primary cultures of human medullary thyroid carcinoma tissue were prepared from lymph node metastases in two patients. The parenchymal, cultured cells displayed positive immunocytochemical staining for CT, and the cells also released the hormone into the culture medium. The membrane potential and resistance of the CT‐producing cells were 50.1 ± 8.9 mV and 634 4±154 Mf2 (mean ± SD, n = 46). TTX sensitive action potentials with maximum rate of rise up to 51 V s‐1 were evoked by current injection in Na+‐containing solution, whereas TTX insensitive action potentials with maximum rate of rise up to 9 V s‐I were generated in Na+‐free solution. These action potentials were reversibly blocked by D‐600. We conclude that the action potentials of the human MTC cells have both a Na+ and a Ca2+ component. Ejection of Ca2+‐free solution close to the cells caused membrane hyperpolarization associated with decreased membrane resistance. The reversal potential of this response was —66.2 ± 10.9 mV (n = 10), indicating that a permeability increase to Cl‐ and/or K+ may be involved. We suggest that elevated plasma Ca2+ concentration in vivo may cause increased excitability due to membrane depolarization and resistance increase, thus leading to enhanced Ca2+ influx and hormone secretion.
Central and peripheral motor effects of morphine on the rat urinary bladder
Authors: SILLÉN U. , RUBENSON A.
Published: December 2008

Intravesical pressure recordings were performed in anaesthetized rats, and the effect of morphine on urinary bladder function was studied. The action of morphine was registered as its influence on bladder hyperactivity induced by central catecholaminergic stimulation with 1‐dihydroxyphenylalanine (L‐DOPA) after peripheral decarboxylase inhibition, and as its action on the response to regional injection of receptor agonists (acetylcholine (ACh), substance P (SP)) and peripheral motor nerve stimulation (PNS). The bladder response to L‐DOPA was inhibited by intracerebroventricularly (i.e.v., fourth ventricle, 10 μg), as well as by systemically administered (1–5 mg kg‐1i.p.), morphine. Intravenous and i.e. v. naloxone antagonised the inhibitory actions of i.v. and i.c.v. morphine, respectively. Regional intra‐arterial administration of morphine (0.01–5 mg) induced a weak bladder contractionper se, with a subsequent slight depression of bladder reactivity to ACh, SP and PNS. It is suggested that the inhibitory effect of morphine on bladder motility in the rat, is mainly mediated by central opioidreceptors. The direct peripheral effects on the detrusor muscle are weak, with an initial contraction followed by slight depression of the reactivity.
Co‐release of neuropeptide Y and catecholamines upon adrenal activation in the cat
Authors: LUNDBERG JAN M. , FRIED GABRIEL , PERNOW JOHN , THEODORSSON‐NORHEIM ELVAR
Published: December 2008

The release of neuropeptide Y (NPY)‐like immunoreactivity (‐LI) in relation to catecholamines from the cat adrenal was studied in anaesthetized animals. Abdominal surgery increased plasma levels of NPY‐LI from 65± 6 to 149 ± 26 pmol 1‐1. A positive veno‐arterial concentration gradient over the adrenal gland was found for both NPY‐LI, adrenaline (Adr) and noradrenaline (NA) during basal conditions. Asphyxia for 2 min increased the output of both NPY‐LI and catecholamines from the adrenal. Electrical stimulation of the splanchnic nerve caused a marked increase in adrenal output of NPY‐LI and catecholamines. The adrenal content of NPY‐LI, as well as the release of NPY‐LI from the adrenal, was at least 1000‐fold lower on a molar basis than that of catecholamines. The concentration of NPY‐LI in the adrenal vein upon splanchnic nerve stimulation was in the nM range. Reversed‐phase HPLC characterization revealed that NPY‐LI in the adrenal, and in the adrenal venous plasma collected during splanchnic nerve stimulation, was closely related to synthetic porcine NPY. Stimulation with bursts of 20 Hz for 1 s with 10 s intervals for 2 min caused a four‐fold higher output of NPY‐LI and Adr compared to a continuous stimulation with 2 Hz, giving the same number of impulses. The NA output, however, was only slightly increased by burst stimulation. Guanethidine did not reduce the adrenal output of NPY‐LI or catecholamines induced by splanchnic nerve stimulation, while the release was abolished by chlorisondamine. NPY enhanced the in vitro contractile activity of Adr and NA on the a. profunda femoris from the cats used in the functional experiments. The threshold concentration of NPY for this enhancement was 250 pM. The NPY in higher concentrations (> 10‐8 M) had contractile effects per se. In conclusion, the present data suggest a functional relationship between adrenal release and effects of NPY and Adr.
Mechanisms underlying pre‐ and postjunctional effects of neuropeptide Y in sympathetic vascular control
Authors: PERNOW JOHN , SARIA ALOIS , LUNDBERG JAN M.
Published: December 2008

The effects of porcine neuropeptide Y (NPY) regarding sympathetic vascular control were studiedin vitroon isolated rat blood vessels. The 10‐9M NPY enhanced (about two‐fold) the contractile responses to transmural nerve stimulation (TNS), noradrenaline (NA) and adrenaline (about two‐fold) in the femoral artery. Higher concentrations of NPY (> 10‐8M) caused an adrenoceptor‐resistant contractionper se.The TNS‐evoked [3H]NA efflux was significantly reduced by NPY in a concentration‐dependent manner (threshold 10‐9M). The calcium antagonist, nifedipine, abolished the contractile effects of NPY and the NPY‐induced enhancement of NA contractions but did not influence the prejunctional inhibition of [3H]NA release. Receptor‐binding studies showed that the ratio of alpha1‐ to alpha2‐adrenoceptors in the femoral artery was 30:1. The NPY did not cause any detectable change in the number of alpha1‐ or alpha2‐adrenoceptor binding sites or in the affinity of alpha2‐binding sites, as revealed by prazosin‐ and clonidine‐binding, respectively. The NPY also inhibited the TNS‐evoked [3H]NA release (by 42–86%) in the superior mesenteric and basilar arteries and in femoral and portal veins. The NPY still depressed TNS‐evoked [3H]NA secretion from the portal vein in the presence of phentolamine. The NPY caused a clear‐cut contraction in the basilar artery, increased the contractile force of spontaneous contractions in the portal vein, while only weak responses were observed in the superior mesenteric artery and femoral vein. The NA‐induced contraction was markedly enhanced by NPY in the superior mesenteric artery, only slightly enhanced in the portal vein and uninfluenced in the femoral vein. In conclusion, in all blood vessels tested, NPY depresses the TNS‐evoked [3H]NA secretion via a nifedipine‐resistant action. Furthermore, NPY exerts a variable, Ca2+‐dependent vasoconstrictor effect and enhancement of NA and TNS contractions.
Effect of renal nerve activity on tubular sodium and water reabsorption in dog kidneys as determined by the lithium clearance method
Authors: ABILDGAARD ULRIK , HOLSTEIN‐RATHLOU NIELS‐HENRIK , LEYSSAC PAUL P.
Published: December 2008

The reliability of the lithium clearance method in studies of the effect of renal nerve activity upon tubular sodium and water handling in the dog kidney was investigated. Following unilateral acute surgical denervation of the kidney a significant increase in urinary flow rate (40 ± 7%), sodium clearance (26 ± 4%), lithium clearance (9 ±2%) and fractional lithium clearance (8 ± 2%) was seen, as compared to the contralateral kidney with preserved innervation. Calculated absolute proximal reabsorption rate decreased significantly by 7 ± 2 %, while calculated absolute rates of distal reabsorption of sodium and water increased significantly by 9 ± 2% and 8 ± 2%. Low‐frequency electrical stimulation of the distal nerve bundle of the denervated kidney caused a significant decrease in urine flow rate (37 ±6%), sodium clearance (31 ±4%), lithium clearance (17 ± 5%) and in fractional lithium clearance (18 ± 5%). Calculated absolute proximal reabsorption rate increased significantly by 17 ± 3%, while calculated absolute rates of distal sodium and water reabsorption decreased significantly by 16 ± 5% and 16 ± 5%. These changes in tubular sodium and water reabsorption during alterations in renal nerve activity occurred without measurable changes in renal blood flow (RBF) and glomerular filtration rate (GFR). Administration of amiloride had no significant effect either on the lithium clearance, RBF or GFR, while the sodium excretion rate increased and potassium excretion rate decreased, supporting that significant distal lithium reabsorption did not occur under the present experimental conditions. The present data suggest that the lithium clearance method is a reliable method for estimating the effect of efferent nerve activity upon proximal and distal tubular reabsorption of sodium and water in the dog kidney.
Further studies on oscillating tubulo‐glomerular feedback responses in the rat kidney
Authors: LEYSSAC PAUL P.
Published: December 2008

Free flow microperfusion (closed feedback loop) experiments in halothane–nitrous oxide‐anaesthetized rats demonstrate two distinct oscillating TGF pressure responses to pertubations in early distal tubular flow. Flow rate changes of 2–8 nl min‐1 induced a 0.02‐0.03 Hz rhythm, while changes above 25 nl min ‐1 often induced a 0.17‐0.18 Hz rhythm in proximal tubular pressures. Following interruption of microperfusion, the intratubular pressure showed an initial undershoot and a gradual oscillating return to the control level. Each nephron responded individually to systemic changes with oscillations differing in frequency, phase and amplitude from that of its neighbour. Postglomerular vascular pressure (Psv) oscillated synchronous with the proximal luminal pressure (Pprox) of the same nephron; the amplitude of the Psv might be larger than that of the corresponding Pprox‐ The Psv decreased by 2–3 mmHg as Henle loop flow was increased by 7 nl min‐1. Furosemide (0.1‐0.2 mM) in the microperfusate abolished the oscillations, and caused Psv and Pprox to increase by 3–4 mmHg. This effect was rapidly reversible.
Regional glucose metabolism in the rabbit brain in control and TRH‐treated animals
Authors: KOSKINEN LARS‐OWE D. , SPERBER GÖRAN O.
Published: December 2008

The local cerebral metabolism in urethane anaesthetized control and TRH‐treated rabbits was studied with the [14C]2‐deoxyglucose method. In the controls, the glucose use was found to be highest in regions known to have a high blood flow and low in regions with low flow. The glucose consumption was, calculated using the constants found by Kennedy et al. in monkeys, 23.5 ± 6.0 μmol 100 g‐1 min‐1 in parietal cortex. The TRH was infused at a dose of 0.06 mg kg‐1 min‐1 which is known to cause vasodilation in the brain. No marked influence of the peptide on the glucose use was detected. It was concluded that the previously reported cerebral vasodilation caused by TRH is not due to an increase in cerebral metabolism.
Sympathetic inhibition after surgical reversal of renovascular hypertension in rats. Role of vagal nerves
Authors: GÖTHBERG GUNNAR , THORÉN PETER
Published: December 2008

The present study was undertaken to study the changes in efferent renal sympathetic nerve activity (RSNA) and heart rate (HR) during the acute fall in blood pressure after surgical reversal of two‐kidney, one‐clip renovascular hypertension in rats, and to explore if cardiopulmonary vagal afferents can influence sympathetic outflow in this situation. In 14 rats with a MAP of 199 ± 6 mmHg the renal artery clip was surgically removed and after 90 min MAP had decreased to 109 ± 7 mmHg. The HR had then decreased by 26 ± 15 beats min‐1 (P < 0.05) and RSNA did not increase as expected, but was somewhat reduced (84 ± 8 % of control). In contrast, lowering pressure with nitroprusside to the same extent produced large and significant increases in HR and RSNA in seven other renal hypertensive rats. Acute bilateral vagotomy was performed in seven of the declipped rats, which induced an immediate increase in MAP (+ 35 ± 10 mmHg, P < 0.05), HR + 28 ± 10 beats min‐1, P < 0.05) and RSNA (+ 51 ± 19%, P < 0.05). A few minutes afterwards the vagotomy pressure again started to fall and was, after another 90 min 107 ± 10 mmHg together with slight reductions in HR and RSNA. Another group of six rats were initially exposed to bilateral vagotomy. In these vagotomized rats declipping also induced hypotension (204 ± 10 to 95 ± 7 mmHg, P < 0.001), together with tendencies of decreases in HR (425 ± 17 to 397 ± 17 beats min‐1) and in RSNA (‐4 ± 6%). In conclusion, this study shows that the response pattern induced by removing a renal artery obstruction is characterized by a slight reduction in heart rate and renal sympathetic nerve activity despite a rapid fall in blood pressure. This suppression of the expected baroreceptor reflex may at least partly be elicited by an activation of caridiopulmonary vagal afferens, since acute bilateral vagotomy induces an immdiate rise in RSNA and HR. However, other unknown mechanisms also contribute.
Disuse as cause of supersensitivity in the rat urinary bladder*
Authors: EKSTRÖM JÖRGEN , MALMBERG LARS
Published: December 2008

Ureterostomiain situwas performed to reduce the nervous reflex activation of the bladders without concomitant hypertrophy. In muscle strips of these disused and non‐hypertrophied bladders, supersensitivity to methacholine was demonstrated, which did not increase between 1 and 3 weeks. The supersensitivity did not increase further by combining urinary diversion with section of the preganglionic bladder nerves (decentralization). From the present results it may be concluded that in decentralized and hypertrophied bladders not only hypertrophyper se, previously studied (Ekströmet al.1985), but also loss of nerve impulse traffic (cf. urinary diversion) contribute to the development of supersensitivity.
Influence of heat exposure on acid/base and fluid balance in hyperhydrated goats
Authors: AUGUSTINSSON O. , HOLST H. , FORSGREN M. , ANDERSSON H. , ANDERSSON B.
Published: December 2008

Hyperhydrated goats were exposed to an environmental temperature of 45 d̀C (relative humidity 70%) for 120 min. After 90 min, rectal temperature and respiratory frequency reached plateau levels of 40.5 d̀C and 280 respirations min‐1, respectively. Measurements of arterial and venous blood acid‐base parameters revealed that respiratory alkalosis had started to develop after 60 min, and had become obvious at the end of the heat exposure period. Renal compensation (evidenced by gradual increases in urinary pH and renal Na excretion) developed in parallel with the respiratory alkalosis. The heat exposure elicited a moderate, temporary inhibition of the water diuresis, but no obvious increase in the renal excretion of arginine vasopressin (antidiuretic hormone, ADH). Preliminary determinations of plasma aldosterone did not show any change during the actual heat exposure period, but a 50% temporary decrease in plasma aldosterone 30 min thereafter. The study confirms the susceptibility of goats to develop respiratory alkalosis during thermoregulatory panting, and shows that this is not to any appreciable extent diminished during hyperhydration. It can further be concluded that a heat‐induced rise in body temperature to 40.5 d̀C is no powerful stimulus for vasopressin release in the hyperhydrated goat. The determinations of plasma aldosterone suggest that reduced liberation of the hormone does not contribute to the immediate renal compensation of respiratory alkalosis, but that respiratory alkalosis reaching a certain intensity inhibits aldosterone secretion.
Pilocarpine‐stimulated salivary flow rate and salivary glucose concentration in alloxan diabetic rats. Influence of severity and duration of diabetes
Authors: REUTERVING C.O.
Published: December 2008

Pilocarpine‐stimulated salivary flow rate and glucose concentration were estimated in short‐term (1 month) and long‐term (12 months) alloxan diabetic rats and in age‐matched nondiabetic controls. Diabetic rats had significantly decreased salivary flow rate which was negatively correlated to blood glucose concentration. They also had increased salivary glucose levels, which were positively correlated to blood glucose values, when the blood glucose values were above 15 mmol 1‐1, suggesting a threshold mechanism for salivary glucose excretion. The long‐term diabetic rats had significantly higher salivary flow rates than the short‐term diabetics. Insulin therapy in short‐term diabetic rats improved the salivary parameters and normalized blood glucose levels, indicating that the salivary abnormalities are reversible ‐ at least in the short‐term perspective ‐ and reflect the metabolic derangements of the diabetes. The results suggest that reduced salivary flow rate and increased salivary glucose concentration might be of importance for the development of the periodontal disease and caries seen in diabetic rats.
The phorbol ester TPA induces hormone release and electrical activity in clonal rat pituitary cells
Authors: C.0STBERG B. , SAND O. , BJ0RO T. , HAUG E.
Published: December 2008

The phorbol ester TPA activates the protein kinase C in a similar way as 1,2‐diacylglycerol. The effect of TPA on prolactin (PRL) secretion and electrical properties of rat pituitary cells in culture (GH4C1 cells) were compared with the effects of thyroliberin (TRH) on the corresponding parameters. The rate of hormone release was measured using a parafusion system optimized to give high time resolution. Samples for PRL measurements were taken every 4 s. The TRH evoked a biphasic PRL release, with a transient peak after about 30 s followed by a lower but sustained enhancement of the secretion. The TPA mimicked the late phase of the secretory response to TRH. The TPA analogue, 4α‐PDD, had no effect on the PRL release. The TRH also evoked biphasic membrane potential changes in the GH4C1 cells; the late phase consisting of membrane depolarisation associated with increased input resistance and enhanced firing of Ca2+ dependent action potentials. The TPA mimicked to a great extent these late phase effects of TRH, whereas the inactive analogue 4α‐PDD was ineffective. Continuous exposure to TPA masked the late phase of the electrophysiological response to TRH, suggesting that TPA and TRH share common mechanisms in their action on GH4C1 cells. We suggest that TRH enhances the electrical activity in these cells due to protein phosphorylation induced by diacylglycerol activation of protein kinase C, which in turn suppresses the membrane permeability to K+.
The adrenergic nervous control of fluid transport in the small intestine of normotensive and spontaneously hypertensive rats
Authors: SJÖVALL H. , ELY D. , WESTLANDER G. , KÖHLIN T. , JODAL M. , LUNDGREN O.
Published: December 2008

Intestinal net fluid transport in normotensive Wistar Kyoto rats (WKR) and spontaneously hypertensive rats of the Okamoto strain (SHR) were studied during ‘rest’, during electrical stimulation of the regional sympathetic fibres as well as after acute denervation and α‐adrenergic receptor blockade (phentolamine). During ‘rest’ no statistically significant difference in fluid transport rate could be demonstrated between WKR and SHR. Cutting the left splanchnic nerve, severing the periarterial nerves or giving phentolamine turned net fluid absorption to net fluid secretion in most SHR, whereas fluid absorption was little influenced in WKR by these procedures. Stimulating the left splanchnic nerve (2, 4, 8 Hz) markedly increased net fluid uptake or decreased net fluid secretion in SHR in a frequency‐dependent manner. A small effect was seen in WKR at a stimulation rate of 4 Hz. The ‘spontaneous’ fluid secretion in denervated intestinal segments of SHR was accompanied by a net chloride secretion. Giving hexamethonium i.v. turned net fluid and chloride secretion into water and ion absorption, suggesting that the secretion was evoked by secretory nervous pathways in the enteric nervous system. It is concluded that the ‘spontaneous’ fluid and electrolyte secretion seen in denervated intestines of SHR is normally ‘concealed’ by an augmented rate of firing in the regional adrenergic nerve fibres controlling fluid and electrolyte transport. The possible importance of the ‘spontaneous’ intestinal secretion in SHR in the patho‐physiology of arterial hypertension is tentatively discussed.
Effects of spinal cord lesions and rhizotomies on cholinergic and opiate receptor binding sites in rat spinal cord
Authors: GILLBERG P.G. , WIKSTEN B.
Published: December 2008

Changes in the distribution of [3H]quinuclidinylbenzilate ([3H]QNB), [3H] alpha‐bungaro‐toxin [3H]alpha‐Btx) and [3H]etorphine binding sites were studied autoradiographically, and cholinacetyltransferase (ChAT) activity radioenzymatically, in the C6–7 segments of rats 1–20 days after combined dorsal and ventral C3–8 rhizotomies and spinal cord lesions at C3. After dorsal and ventral rhizotomies the number of [3H]QNB, [3H]alpha‐Btx and [3H]etorphine binding sites were reduced ipsilaterally in the dorsal horn and those of [3H]QNB and [3H]alpha‐Btx in the ventral horn. In the ventral horn ChAT activity was significantly reduced. After a unilateral spinal cord lesion at C3, ChAT activity was reduced in the ipsilateral ventral horn at C6–7 caudal to the lesions, whereas no change in receptor binding sites was observed.
Erythropoiesis‐stimulating factor(s), erythropoiesis and erythrocyte 2,3‐diphospho‐glycerate in young rabbits with marked postnatal fall in haemoglobin
Authors: HOLTER P. H. , SANENGEN T. , HALVORSEN S. , REFSUM H. E.
Published: December 2008

The erythropoietic activity and erythrocyte 2,3‐diphosphoglycerate (2,3‐DPG) were studied during and after the nadir of the post‐natal anaemia in normal, rapidly growing rabbits, from the 12th to the 35th day after birth. Whole blood haemoglobin (Hb) decreased from 9.3 g dl‐1 on the 12th to 4.9 g dl‐1 on the 25th day, while erythropoiesis‐stimulating factor(s) (ESF) in plasma (determined by a cell culture assay) concomitantly rose from undetectable to high levels. In spite of marked rise in body weight, from 250 to 480 g, estimated haemoglobin mass (Hb mass) and reticulocyte mass production rate (Rt prod) remained essentially the same, about 1.8 g and 0.3 ml day‐1. From the 25th to the 35th day, ESF decreased to a lower level, while Hb increased to 10.8 g dl‐1 and Hb mass and Rt prod rose sharply, to 6.9 and 1.2 ml day‐1. The 2,3‐DPG rose markedly during the observation period, but showed a transient decline on the 29th day, simultaneously with the peak in reticulocyte counts (Rt) (24%) and release of young erythrocytes with low 2,3‐DPG. The data indicate that the regions governing the erythropoietin production/release became increasingly sensitive to hypoxia during the observation period. The possibility also exists that the increase in ESF was due only in part to hypoxic stimulation. It could be related to the maturation of the animal in other ways, such as shift from extra‐renal to renal erythropoietin production and the growth. The lack of response to increasing stimulation indicates that the erythropoiesis was restricted by the availability of iron and/or other factors necessary for erythrocyte and haemoglobin production.
Temperature effects on catecholamine accumulation in neuronal and extraneuronal compartments in the cod spleen
Authors: UNGELL A.L.
Published: December 2008

The effects of temperature on the accumulation of radiolabelled adrenaline and noradrenaline were studied in the perfused spleen of the Atlantic cod,Gadus morhua.A decrease in temperature from 20–24 to 10 d̀C showed a corresponding decrease in the neuronal and extraneuronal accumulation of both adrenaline and noradrenaline. The Q10‐values for the neuronal accumulation of adrenaline and noradrenaline were 3.6 and 2.1, respectively. This indicates that adrenaline is accumulated neuronally by an active process. An increased perfusing time resulted in an even more pronounced difference in the neuronal accumulation between the two amines. The extraneuronal accumulation of both amines was only slightly affected by a 10 d̀C decrease in temperature, and with increasing perfusion time, the accumulation increased as in a passive diffussion. There are strong indications that adrenaline and noradrenaline not only accumulate differently from each other in the adrenergic neurons of the cod spleen, but also that the adrenaline uptake mechanism neuronally might resemble the characteristic mammalian catecholamine uptake while noradrenaline seems to accumulate by a more primitive mechanism, not sensitive to a reduction in temperature. This might be physiologically important for the cod, since the spleen can synthetize adrenaline from noradrenaline and the uptake of adrenaline from the circulation is therefore less important.
The relation between intradental nerve activity and pulpal pain after heat stimulation
Authors: AHLQUIST M. L. , FRANZÉN O. G. , EDWALL L. G. A. , FORS U. G. , HAEGERSTAM G. A. T.
Published: December 2008

The effects of tooth surface stimulation on intradental nerve activity (INA) and subsequent pain perception were studied in human lower incisors later to be extracted for periodontal reasons. The INA elicited by hot guttapercha briefly applied to the tooth surface was monitored by means of labial electrodes deeply implanted in the dentin and perceived pain was continuously rated using a finger‐span technique. After each stimulation the subject was also requested to select a sensory descriptor that was appropriate to describe the maximal pain intensity. The very first application of heat induced a typical pattern of nerve activity consisting of three phases. An initial burst of 3–5 s duration, phase I, was followed by a depression relative to the baseline lasting for 20–30 s, phase II, that gradually turned into phase III constituting a slowly increasing firing rate. The spontaneously emerging activity (phase III) in the absence of a physical stimulus passed unnoticed by all the subjects despite an average increase in firing rate of 67% relative to the prestimulus noise level. Repeated heat applications at short intervals led to a decrease and finally to abolishment of the whole nerve response. The lack of pain during phase III may be explained in two ways: (i) the rate of increase in firing frequency may be too slow to trigger those perceptual pathways involved in processing of pain; (ii) the slow development of the increased sensory nerve activity may lead to central habituation. It is concluded that the third phase of the triple response to heat is an electrophysiological sign of hyperexcitability of the pulpal A‐delta nerves due to an inflammation in its initial state. On the basis of the present findings we would like to caution against the use of repeated heat stimulation of teeth since it may induce damage in the pulp organ, especially in teeth with advanced periodontal disorders.
Effects of small changes of plasma vasopressin on subcutaneous and skeletal muscle blood flow in man
Authors: HAMMER M. , SKAGEN K.
Published: December 2008

The effect of vasopressin (AVP) on subcutaneous blood flow was studied by the133Xenon wash‐out method in 13 healthy subjects during three consecutive infusions of synthetic AVP, using increasing infusion rates. In seven of them, both subcutaneous and skeletal muscle blood flows were measured during the first infusion. The preinfusion, and infusion pAVP levels were 1.6 ± 0.4, 34 ± 0.4, 4–9 ± 0.5 and 8.8 ± 0.7 PS ml‐1, respectively (mean ± SE). The values are within the range normally found during dehydration. During the AVP infusions, the blood flow in subcutaneous tissues decreased 30–40% and the vascular resistance increased 60–80%. Neither heart rate nor blood pressure changed significantly during the infusions. Plasma renin activity(PRA)decreased significantly. After cessation of the infusions, blood flow and vascular resistance rapidly returned to preinfusion values, while PRA increased very slowly. Skeletal muscle and subcutaneous tissues blood flows were found to be equally sensitive to small changes in the pAVP level. The present study has demonstrated that even minor increments of pAVP levels, as seen during dehydration, can significantly alter the regional blood flow in subcutaneous and skeletal muscle tissues in man.
The effect of isoflurane on unmyelinated and myelinated fibres in the rat brain
Authors: BERG‐JOHNSEN J. , LANGMOEN I. A.
Published: December 2008

The effect of isoflurane on unmyelinated and myelinated fibres of the rat brain was investigatedin vitro.The amplitude of the unmyelinated fibre potential (the prevolley of the hippocampal CAi region) was reduced in a dose‐dependent manner with increasing isoflurane concentrations (up to 5 %). The conduction velocity was slightly decreased. The minimal alveolar concentration (MAC) anaesthetizing 50% of the animals is 1.38%. At this concentration the presynaptic volley was reduced by 18% and the conduction velocity was decreased by about 1 %. The effect on myelinated fibres (fimbria) was small and significantly different from the effect on unmyelinated fibres (P= 0.03 and 0.005 at 1 and 2% isoflurane, respectively).
Leakage of macromolecules from guinea‐pig tracheobronchial microcirculation. Effects of allergen, leukotrienes, tachykinins, and anti‐asthma drugs
Authors: PERSSON C. G. A. , ERJEFALT I. , ANDERSSON P.
Published: December 2008

The tracheobronchial mucosa of anaesthetized guinea‐pigs (normal or sensitized with ovalbumin to produce IgE and IgG antibodies) was superfused (0.02 ml min‐1, 5 min) with saline, mediators, and (in sensitized animals) ovalbumin via a catheter atraumatically introduced orally. The intravascular blood pool and amount of macromolecules in excised trachea and adjoining main bronchi were quantified by measuring erythrocytes, that had been labelledin vivowith99Tcm, and analysing for FITC‐dextran, MW = 70,000, that had been given i. v. Extravasation of macromolecules was determined as the analysed total content minus the calculated intravascular content of FITC‐dextran. Capsaicin 0.1 nmol extravasated 223 μg of FITC‐dextran per g wet weight of airway tissue (P< 0.001). Substance P 0.1 nmol, 41 μg g‐1(P> 0.05); substance P 0.3 nmol, 142 μg g_1(P< 0.001); eledoisine 0.1 nmol, 101 μg g_1(P> 0.01); ovalbumin 0.1 μg, 179 μg g‐1(P< 0.001); LTC4, 0.2 pmol, 180 μgg‐1(P< 0.001); LTD40.2 pmol 223 μg ml‐1(P< 0.001). Bronchi and trachea were similarly affected by these agents. Prior superfusion. (0.02 ml min‐1, 30 min) with terbutaline 0.06 nmol, enprofylline 12 nmol, or lidocaine 6 nmol significantly reduced the effect of capsaicin. Enprofylline also reduced significantly the effect of LTC4. The degree of extrevasation in this study was smaller than could be detected by changes in tissue wet to dry weight ratios. The present data support the view that tracheobronchial vasculr permeability to macro‐molecules is subject to physiological and pharmacological control.
Inhibitory effects of chemically‐different ‘loop’ diuretics on chloride transport across the bullfrog cornea
Authors: ERIKSSON Ö. , WISTRAND P. J.
Published: December 2008

Frog (Rana catesbeiam) corneas were mounted in an Ussing chamber, modified to facilitate dissection and to avoid edge damage to the epithelial tissue during mounting and measurements. When bathed in Conway solution of pH 7.4 the corneas displayed highly stable electrical properties, with a transepithelial potential difference (PD) of 16.6 ± 1.0 mV and a short‐circuit current (SCC) of 10.3 ± 0.8 μA cm‐2. The DC resistance was 2.0 ± 0.15 k. cm2(mean ± SE,n= 45). An increase in the intracellular cyclic AMP level induced by prostaglandin E2and by 3‐isobutyl‐i‐methylxanthine (IBMX) resulted in an increase in SCC. Ortho‐vanadate, an inhibitor of Na+‐K+‐ATPase, reduced SCC. The acidic loop diuretics furosemide, bumetanide and the le vorotatory form of indacrinone (MK‐196) reduced SCC byaboutso%at concentrations of 500,100 and 46 μM, respectively. The (–)form of MK‐196 was four times more active than the (+)form. Dimethylation of the SO2NH2group reduced the activity of bumetanide. The basic diuretics muzolimine (Bay G 2821) and MK‐447, were found, similarly, to reduce SCC by about 50% at concentrations of 500 μM. In view of their ‘high ceiling’ type of saluretic effects in whole animals, these basic agents should therefore be classified as ‘loop’ diuretics. The effects of these structurally highly different ‘loop’ diuretics are similar in epithelia which secrete (cornea) and in those which absorb (the renal thick ascending limb of Henle's loop; TALH) chloride ions. This could indicate that they interact with the same ‘diuretic receptor’ and have a common mode of action in both types of epithelia. Moreover, their effects on chloride transport parallel their saluretic effects. Amphibian cornea should therefore be a convenient model tissue for studies of the modes of action and the structure‐activity relationships of loop diuretics.
Indacrinone (MK‐196) ‐ a specific inhibitor of the voltage‐dependent CI‐ permeability in toad skin
Authors: DÜRR J. E. , LARSEN E. HVIID
Published: December 2008

The effect of indacrinone (MK‐196) on Cl‐transport through toad (Bufo bufo) skin epithelium was studied by the voltage clamping technique. At the transepithelial potential, V = 50 mV (serosal bath grounded) the unidirectional fluxes, governed by a Cl‐self‐exchange diffusion pathway, were not affected by 1 mM racemic MK‐196 in the outer bath. Likewise at V = 0 mV, the unidirectional fluxes as well as the active (net) inward flux of Cl‐were unaffected by MK‐196. Voltage clamping the epithelium in the physiological range of potentials activated a Cl‐specific passive conductance that saturated for V ±– 90 mV. The influx and efflux of Cl‐through this pathway were inhibited by MK‐196, and the (passive) Cl‐current was inhibited in a dose‐dependent way for [MK‐196] ± 50 μM with about 70% inhibition for [MK‐196] = I mM. The maximum Cl‐conductance was decreased without shifting the position along the V‐axis of the inverted S‐shaped conductance–voltage relationship. The time constants for the voltage‐stimulated Cl‐conductance activation were not affected by MK‐196 (50 μM ± [MK‐196] ± 1 mM). The (+) and (–) isomers and racemic MK‐196 affected the voltage‐dependent Cl‐conductance in similar ways. It is concluded that MK‐196 has the properties of a Cl‐channel blocker which is specific for the voltage‐dependent Cl‐permeability of the epithelium. The time course for development of inhibition exhibited a fast (min) and a slow (h) component. The fast component may reflect a direct interaction of MK‐196 with an extracellular site of the Cl‐channel, whereas the slow one may reflect impairment of a metabolic pathway regulating the Cl‐permeability, or an interaction of MK‐196 with a cytoplasmic site of the anion permeation pathway.
Naloxone and haemorrhagic hypotension in rats. Evidence against sympathetic nervous system as the primary mediator of improved cardiovascular haemodynamics
Authors: MANSSON J. , SKOOG P. , THORÉN P.
Published: December 2008

Release of endogenous opiate‐like substances seem to occur in different forms of stress. Earlier studies have shown that the opiate antagonist, naloxone, has a positive effect on cardiac performance and blood pressure in animals with haemorrhagic shock. In the present study, we have examined the involvement of the sympathetic nervous system in this response. Two groups of anaesthetized normotensive Wistar‐Kyoto rats were studied. Both groups were bled rapidly (about 5 min) down to an arterial pressure of 50 mmHg and were kept at that level for 30 min. At the end of the 30‐min bleeding period, naloxone 1, 2, or 5 mg kg‐1 was injected i.v. in a small volume of saline. In the first group of rats (n= 6), the aortic pressure was kept constant at 50 mmHg by further bleedings after naloxone. In the other group (n= 7), the arterial pressure was allowed to rise after naloxone. As reported earlier, haemorrhagic hypotension caused a pronounced inhibition of renal sympathetic nerve activity. Naloxone injected after 30 min of hypotension caused an immediate rise in blood pressure, followed 1–2 min later by a rise in sympathetic nerve activity (SNA). In animals in which pressure was held constant by further bleeding after naloxone, only small and insignificant changes in SNA were observed. The conclusions are the following: injection of naloxone increases blood pressure in rats exposed to severe haemorrhage (Faden & Holiday 1979). The rise in aortic pressure is followed 1–2 min later by a rise in SNA. Our data speaks against a role of central endorphin systems as being the primary mechanism by which naloxone increases blood pressure in haemorrhagic shock.
24‐h evaporative and sensible heat losses in relation to ambient humidity at 24 °C in clothed human subjects
Authors: GARBY L. , LAMMERT O. , NIELSEN E.
Published: December 2008

The effect of ambient humidity on the energy expenditure of clothed subjects was investigated. Fifty‐six healthy men and women, weighing about 65 kg, spent 24 h in a large human calorimeter at 24 °C and performed either of two fixed activity programmes. The ambient humidity varied between experiments from 3 to 11 g m‐3. The sensible heat output did not vary significantly with humidity but the evaporative heat loss decreased by about 1.5 W for each g m‐3 increase in humidity.