bluuebunny/crossref_metadata_2025 huggingface dataset:
Agonist and antagonist characterization of the P2‐purinoceptors in the guinea pig ileum
Authors: WIKLUND N. PETER , GUSTAFSSON LARSE.
Published: December 2008

When adenine nucleotides were administered to isolated guinea pig ileum longitudinal muscle, two immediate effects were observed: a contractile effect and a concomitant inhibition of the responses elicited by transmural nerve stimulation. At concentrations up to 10‐4mthe order of potency for the contractile effect was α,β‐MeADP =α,β ‐MeATP > ADP = ATP = AMPPNP =β,t‐MeATP > 2′‐deoxy AMP = 2′‐deoxy ADP. AMP and adenosine did not show any contractile effect, whereas both compounds dose‐dependently and reversibly inhibited the nerve‐induced contractile responses. ADP, ATP, β,t‐MeATP and AMPPNP also inhibited contractile responses to transmural nerve stimulation, whereas 2′‐deoxy AMP, 2′‐deoxy ADP, α,β ‐MeADP and α,β ‐MeATP showed but weak inhibitory effects, 2′‐deoxyadenosine, IMP, IDP, ITP, 8‐BrATP and TDP lacked significant contractile effects and did not exert a significant inhibition on nerve‐induced contractions.p‐chloromercuribenzene sulphonic acid (PCMBS) irreversibly antagonized the contractile effects of ADP, ATP and the α,β ‐methylene derivatives, whereas dantrolene sodium, tetrodotoxin, scopolamine and 8‐p‐sulphophenyltheophylline were without effect on nucleotide‐induced contractions.

The contractile effect of ADP or ATP was unaffected by indomethacin, whereas the contractile effect by α,β ‐methylene derivatives was abolished by indomethacin. ADP, ATP and α,β ‐MeADP enhanced contractile responses to exogenous acetylcholine, α,β‐MeADP being most effective. This enhancement was blocked by indomethacin. We suggest that ADP and ATP contracted the guinea pig ileum by an action at postjunctional P2‐purinoceptors with different characteristics from prejunctional P1‐purinoceptors. The α,β‐methylene analogues seemed to act at least at one different excitatory site and promotion of prostaglandin biosynthesis was critical for their effect.
Increased plasma levels of oxytocin in response to afferent electrical stimulation of the sciatic and vagal nerves and in response to touch and pinch in anaesthetized rats
Authors: STOCK S. , UVNÄS‐MOBERG K.
Published: December 2008

This study was performed in order to investigate whether activation of sensory fibres within the sciatic and vagal nerves might influence the release of oxytocin. In anaesthetized rats the sciatic and vagal nerves were stimulated electrically in an afferent direction with a variety of stimuli. Rats were also stroked on their backs or nociception was inflicted by pinching a foot. Plasma oxytocin levels were measured with a highly sensitive radioimmunoassay in samples drawn from the carotid artery. Afferent electrical stimulations of both sciatic and vagal nerves at 5 V, 0.2‐2 ms and 3–10 Hz caused immediate significant elevations of oxytocin levels. Thus, basal levels increased by 30–184%. Furthermore, in response to touch and nociceptive stimuli, oxytocin levels rose by 181 % and 206%, respectively. These data indicate that oxytocin can be released by stimulation of peripheral nerves originating in the skin and/or muscle and in the gastrointestinal tract and thus these organs may be involved in the control of oxytocin secretion.
Possible involvement of neuropeptide Y in sympathetic vascular control of canine skeletal muscle
Authors: PERNOW J. , KAHAN T. , HJEMDAHL P. , LUNDBERG J. M.
Published: December 2008

Sympathetic nerve stimulation (2 min, 2 and 10 Hz) increased perfusion pressure in the blood perfused canine gracilis muscle in situ after pretreatment with atropine, desipramine and beta‐adrenoceptor antagonists. This vasoconstriction was accompanied by clear‐cut increases in the overflow of endogenous noradrenaline (NA) at both frequencies and, at 10 Hz but not at 2 Hz, also of neuropeptide Y‐like immunoreactivity (NPY‐LI). The irreversible alpha‐adrenoceptor antagonist phenoxybenzamine enhanced the nerve stimulation induced overflows of NA and NPY‐LI five‐ to eightfold and threefold, respectively. The fractional overflows of NA and NPY‐LI per nerve impulse were similar in response to the high‐frequency stimulation, indicating equimolar release in relation to the tissue contents of the respective neurotransmitter. The maximal vasoconstrictor response elicited by 10 Hz was reduced by about 50% following a dose of phenoxybenzamine which abolished the effect of exogenous NA and the remaining response was more long‐lasting. Local i.a. infusion of NPY evoked long‐lasting vasoconstriction in the presence of phenoxybenzamine, while the stable adenosine 5′‐triphosphate (ATP) analogue α‐β‐methylene ATP was without vascular effects. Locally infused NPY reduced the nerve stimulation evoked NA overflow by 31% (P <0.01) at 1 μM in arterial plasma, suggesting prejunctional inhibition of NA release. In conclusion, NPY‐LI is released from the canine gracilis muscle upon sympathetic nerve stimulation at high frequencies. There is nerve stimulation evoked vasoconstriction, which is resistant to alpha‐adrenoceptor blockade. This may in part be mediated by NPY released together with NA from the sympathetic vascular nerves.
Influence of renal denervation on vascular responsiveness of isolated rat intrarenal arteries
Authors: HÖGESTÄTT E. D. , JOHANSSON O. , ANDERSSON K.‐E. , KULLENDORFF C.‐M.
Published: December 2008

Microsurgical renal denervation of the rat has been reported to increase blood loss and bleeding time after a standardized kidney resection. To investigate the vascular effects of denervation, isolated intrarenal arteries were studied using sensitive ‘isometric’ recording equipment. Four pieces of evidence were obtained to indicate an effective functional denervation 1 week after renal nerve transection: (i) Phentolamine reduced the K+‐induced contraction in controls but not in denervated arteries, (ii) The K+‐induced contraction was significantly smaller in denervated than in control arteries, (iii) Noradrenaline (NA) was a significantly more potent vasoconstrictor (4 x) in denervated than in control arteries, (iv) Cocaine increased the NA sensitivity in control arteries (3 x), whereas it failed to do so in denervated vessels. Vasopressin, 5‐hydroxytryptamine (5‐HT), NA (in the presence of cocaine), prostaglandin F2α(PGF2:α) and dopamine (DA) produced concentration‐dependent contractions in the mentioned order of potency. Denervated arteries were found to be about two to three times more sensitive to the vasoconstrictors than control arteries. Angiotensin I and II had no contractile effect in any of the vessel segments examined. Indomethacin‐pretreated arteries also failed to respond to angiotensin II. Neuropeptide Y produced only weak contractions and failed to influence the NA concentration‐response relationship in either control or denervated arteries. In conclusion, renal denervation caused a general supersensitivity of the vascular smooth muscle cells to both circulating and non‐circulating vasoconstrictors. Our results cannot explain the increased blood loss and bleeding time seen after denervation, but rather support the view that the enhanced bleeding was caused by an interrupted vasoconstrictor influence of the sympathetic nerves.
Furosemide causes acute and long‐term hyperglycaemia and reduces glucose tolerance in mice
Authors: SANDSTRÖM P.‐E. , SEHLIN J.
Published: December 2008

The effect of furosemide on carbohydrate metabolism was studied in mice. Single‐dose administration (200 mg kg‐1body weight) resulted in transient hyperglycaemia and a rise in the glucose/insulin ratio within 60 min. The glucose tolerance was impaired with elevated serum glucose and reduced insulin response 2 h after the furosemide injection, but had recovered within 24 h. In mice made hypoglycaemic by prior injection of insulin, the basal serum glucose and the glucose tolerance were impaired 22 h after the injection of furosemide. It is suggested that furosemide has both acute and long‐term effects on carbohydrate metabolism in mice and that, at least in part, this is due to reduced insulin secretion. Glucose may protect against the diabetogenic action of furosemide.
Sympathetic vascular control of the pig nasal mucosa: (I) increased resistance and capacitance vessel responses upon stimulation with irregular bursts compared to continuous impulses
Authors: LACROIX J. S. , STJÄRNE P. , ÄNGGÅRD A. , LUNDBERG J. M.
Published: December 2008

An in vivo model is described in which pentobarbital anaesthetized pigs were used to study the sympathetic nervous control of the nasal mucosal vascular bed. Changes in blood flow in the sphenopalatine artery (representing nasal blood flow) and in the volume of the nasal cavity (mainly reflecting blood content in venous sinusoids), upon electrical stimulation of the cervical sympathetic trunk, were recorded simultaneously. Single impulses (15V, 5 ms) reduced both the arterial flow and the volume of the nasal mucosa. The effects of nerve stimulation with a continuous train of impulses at 0.59, 2 and 6.9 Hz were compared with those caused by stimulation with the irregular bursting pattern, triggered by recorded human sympathetic vasoconstrictor nerve activity, with the same average frequencies. Both types of stimulation reduced nasal blood flow and volume, but the responses were significantly larger with burst stimulation at 0.59 Hz. The volume reduction was already maximal at 0.59 Hz while the blood flow response increased further higher frequencies. Local intra‐arterial pretreatment with the α‐adrenoceptor antagonist phenoxybenzamine significantly attenuated the flow and volume responses to single impulses, while clear‐cut reductions in blood flow (by 40%) and volume (by 80%) remained, upon stimulation, at 6.9 Hz. Noradrenaline given intra‐arterially caused a dose‐dependent reduction in nasal blood flow and volume. The noradrenaline effects were blocked by phenoxybenzamine treatment.

The results show that the pig nasal mucosa represents a model where both blood flow and volume changes can be studied in parallel in vivo. Furthermore, stimulation with the firing pattern of human vasoconstrictor nerves, i.e. irregular bursts, causes larger vascular responses in the pig nasal mucosa compared to a continuous stimulation. The large residual vascular responses to sympathetic nerve stimulation at high frequency after a‐adrenoceptor blockage may be mediated by some other non‐adrenergic transmitter substance(s).
Differential vasomotor action of noradrenaline, serotonin, and histamine in isolated basilar artery from rat and guinea‐pig
Authors: CHANG J.‐Y. , HARDEBO J. E. , OWMAN CH.
Published: December 2008

Vasomotor effects of the amines, serotonin (5‐hydroxytryptamine; 5‐HT), noradrenaline (NA) and histamine, were studied in isolated basilar arteries (BA) of the rat and guinea‐pigin vitro.5‐HT produced marked contraction in rat BA, about 70% of that induced by high (124 mM) K+solution. This response was inhibited by the specific 5‐HT2receptor antagonist, ketanserin, with a pA2value of 9.35. In the guinea‐pig, 5‐HT caused only moderate contraction amounting to 30% of that produced by K+. Ketanserin at concentrations up to 10‐6M showed a comparatively small, non‐surmountable inhibition of the contraction.EC50values for 5‐HT in the guinea‐pig and rat were 5.65 times 10‐8m and 3.70 times 10‐7M, respectively. NA had no effect on rat BA, but moderately contracted guinea‐pig BA. The contraction was not altered by yohimbine but was inhibited by prazosin. Histamine contracted guinea‐pig BA with a maximum that was 110% of the K+‐induced contraction. It was not changed by the H2antagonist, cimetidine. The H1antagonist, pyrilamine, caused competitive inhibition with a pA2of 9.20 at a slope of 0.94. In preconstricted rat BA, histamine induced vasodilatation in a concentration‐dependent manner. The Hj agonist, pyridylethylamine (PEA), and the H2agonist, impromidine, dilated less effectively than histamine. The vasodilatation induced by histamine was inhibited by the H2antagonist, cimetidine, and to a smaller extent by the H1‐receptor antagonist, pyrilamine. Removal of the endothelium abolished the vasodilator effect of PEA but not that of impromidine. In vessels with intact endothelium, the vasodilatation caused by histamine was slightly reversed by pyrilamine, which did not affect the dilatation in endothelium denuded vessels. Cimetidine markedly reversed this vasodilator effect in both intact and endothelium denuded preparations; in the latter the counteraction was almost complete. In precontracted guinea‐pig vessels, histamine failed to induce dilatation even in the presence of the H1antagonist, pyrilamine. Thus, 5‐HT‐induced contraction is mediated by 5‐HT2receptors in the rat and probably by 5‐HT1receptors in the guinea pig. NA failed to contract rat BA but contracted guinea‐pig BA through α1receptors. Histamine was a potent dilator agent in rat BA through a combination of both H1and H2receptors. The dilatation mediated by the H1receptors, but not that mediated by H2receptors, was endothelium‐dependent. Histamine caused strong vasoconstriction in the guinea‐pig BA through H1receptors.
Differing expression of insulin‐like growth factor I in the developing and in the adult rat cerebellum
Authors: Andersson I. K. , EDWALL D. , NORSTEDT G. , ROZELL B. , SKOTTNER A. , HANSSON H.‐A.
Published: December 2008

Insulin‐like growth factor I (IGF‐I; somatomedin C) is a trophic peptide of importance for the development of several tissues and organs. In the present study we have mapped the cellular distribution and dynamic changes of IGF‐I immunoreactivity in the rat cerebellum from its postnatal development to maturity. In vitro hybridization of IGF‐I mRNA was used to demonstrate that the IGF‐I immunoreactive material was synthesized in the cerebellum during a limited time period of cerebellar differentiation.

IGF‐I immunoreactivity was absent in primordial nerve cells but was present in neuroglial cells during the first two days after birth and then rapidly increased in intensity in the latter during the next few days. Proliferative nerve cells in the external granular layer did not express IGF‐I immunoreactivity, while migrating and differentiating nerve cells as well as neuroglial cells showed intense labelling. Starting about 2 weeks postnatally, the IGF‐I immunoreactivity declined, first in the neuroglial cells and eventually in the nerve cells. No IGF‐I immunoreactivity could be demonstrated in the normal adult cerebellum. Colchicine pretreatment did, however, enable demonstration of IGF‐I immunoreactivity in adult cerebellar nerve cells but not in neuroglial cells. In vitro hybridization revealed IGF‐I mRNA in the developing cerebellum but only at very low levels in the adult cerebellum.

It is concluded that IGF‐I is likely to be a factor of importance for the development and maturation of nerve cells and neuroglial cells in the brain. The neuroglial cells in normal adult cerebellum as well as in other parts of the central nervous system do not show any IGF‐I immunoreactivity, in contrast to neuroglial cells in the automatic and peripheral nervous systems.
Calcitonin gene‐related peptide: release by capsaicin and prolongation of the action potential in the guinea‐pig heart
Authors: FRANCO‐CERECEDA A. , LUNDBERG J. M. , SARIA A. , SCHREIBMAYER W. , TRITTHART H. A.
Published: December 2008

The mechanisms underlying the stimulatory effects of capsaicin on the contractility of the guinea‐pig heart were studiedin vitro. Capsaicin (10‐1to 10‐5M) caused an increased overflow of immunoreactive material, suggesting release of calcitonin gene‐related peptide (CGRP)‐and neurokinin A (NKA)‐like immunoreactivity (‐LI), but not of neuropeptide Y (NPY)‐LI from the isolated Langendorff‐perfused whole heart. The capsaicin‐induced release was calcium‐dependent. During exposure to capsaicin, the heart rate was increased, while the contractile force was reduced. In addition to releasing CGRP and NKA‐LI, potassium (60 mM) also increased the overflow of NPY‐LI. The potassium‐induced release of peptides was less calcium‐dependent than the response to capsaicin. Considerably higher tissue levels of CGRP‐LI were found in the atria (about 30 pmol g‐1) than in the ventricles (about 10 pmol g‐1). In experiments on the right atria using transmembrane action‐potential recordings of myocytes, CGRP induced a prolongation of the action potential concomitantly with an increase in rate and contractile force, which was similar to the effect of noradrenaline. Furthermore, CGRP increased the contractile force and relaxation velocity of the electrically stimulated atria. Capsaicin (10‐7M) also increased the duration of the atrial action potential. In conclusion, CGRP‐like material is released by capsaicin from the isolated guinea‐pig heart. Both CGRP and capsaicin prolong the plateau phase of the action potential of atrial myocytes. Therefore, the present data give further evidence that CGRP release from sensory nerves within the heart underlies the cardiostimulatory actions of capsaicin.
Effects of acute haloperidol treatment on regional catecholamine levels and utilization in rats exposed to toluene
Authors: VON EULER G. , FUXE K. , HANSSON T. , ENEROTH P. , AGNATI L. F. , HÄRFSTRAND A. , GUSTAFSSON J.‐Å.
Published: December 2008

The aim of the present investigation was to evaluate whether the responses of central catecholamine (CA) neurons to CA receptor blockade by haloperidol are altered upon toluene exposure. Male rats were exposed to air or toluene (80 ppm) for 5 and 4 days, 6 h day‐1. CA levels and utilization were determined in discrete regions of the forebrain and hypothalamus as well as in the substantia nigra (SN) and anteromedial frontal cortex (AMFC). Serum levels of corticosterone, thyroid stimulating hormone, luteinizing hormone and prolactin were determined by radioimmunoassay procedures. Toluene exposure led to increased dopamine (DA) utilization in the AMFC and increased CA utilization in the paraventricular hypothalamic nuclei. In air‐exposed rats haloperidol (1 mg kg‐1, i.p., 2 h before killing) increased DA utilization in the marginal part of the nucleus caudatus putamen (CAUD). In toluene‐exposed rats, haloperidol induced significant depletions of DA stores in the SN and in the medial and central parts of the CAUD. In the posterior nucleus accumbens (ACC) DA utilization was significantly increased. Combined haloperidol and toluene treatment selectively decreased DA levels in the ACC and SN, and significantly increased DA utilization in the CAUD, as compared with the air‐exposed control group. Furthermore, after combined treatment, there was a specific increase in noradrenaline (NA) utilization in the SN and in CA utilization in the medial palisade zone of the median eminence. Serum prolactin levels were substantially raised in both the air and toluene groups after the haloperidol treatment. In conclusion, acute haloperidol treatment preferentially reduces DA levels and increases DA and NA utilization in the SN and in discrete tel‐ and diencephalic areas in rats exposed to toluene.
Chronic uridine treatment reduces the level of [3H]spiperone‐labelled dopamine receptors and enhances their turnover rate in striatum of young rats: relationship to dopamine‐dependent behaviours
Authors: FARABEGOLI C. , PICH E. MERLO , CIMINO M. , AGNATI L. F. , FUXE K.
Published: December 2008

The effect was studied of chronic uridine treatment on the recovery of striatal D‐2 dopamine (DA) receptors after their irreversible blockade byN‐ethoxycarbonyl‐2‐ethoxy‐1,2‐dihydroquinoline (EEDQ) in young (40 days old) and adult (14 months old) male rats using [3H]spiperone as radioligand. Chronic uridine treatment (15 mg kg‐1day‐1, i.p., 14 days) causes a reduction of [3H]spiperone binding sites in striatum of young rats. This treatment also produces an increase in the rate of recovery of striatal [3H]spiperone‐labelled DA receptors in young, but not in adult rats. Catalepsy and exploratory locomotor activity, two behaviours associated with blockade versus activation of DA receptors, were evaluated in the same rats. The behavioural recovery from the EEDC^induced syndrome is more rapid in the young rats treated with uridine than in the saline‐treated group. The behavioural recovery in old rats was not affected by chronic uridine treatment. Thus, in young rats the pyrimidine nucleoside uridine may modulate the steady state and the turnover rate of striatal D‐2 DA receptors.
Tetrodotoxin‐resistant contractions induced by electrical stimulation of bladder muscle from man, rabbit and rat
Authors: FOVAEUS M. , ANDERSSON K.‐E. , ANDERSSON P. O. , MALMGREN A. , SJÖGREN C.
Published: December 2008

Isolated detrusor preparations from man, rabbit and rat were suspended in an organ bath and isometric tension was recorded. The preparations were stimulated electrically in the presence of Bay K8644 and nifedipine before and after neuronal blockade with tetrodotoxin. Transmural electrical stimulation produced frequency‐dependent contractions in all preparations. Bay K8644 significantly increased and nifedipine decreased these contractions. TTX effectively suppressed the response to electrical field stimulation in all species. When Bay K8644 was added to TTX blocked preparations, the responses to electrical stimulation were partly restored in bladder strips from man and rat. No increase in response was seen in the rabbit preparations. However, if the extracellular K+‐concentration was increased to 10 mM (whichper sedid not affect the response) Bay K8644 significantly increased the contractions. All responses elicited by electrical stimulation in the presence of TTX were abolished by nifedipine. It is concluded that if the bladder smooth muscle is exposed to factors that can increase its sensitivity to contractile agents, this may result in uncontrolled (unstable) bladder contractions. Such contractions may use the ‘normal’ transmitter substances, but may be triggered at a lower stimulus intensity than normal. As a non‐specific increase in membrane excitability seems to be associated with an influx of calcium through voltage‐sensitive calcium channels, calcium antagonists, together with agents specifically blocking relevant transmitter substances, would offer an effective therapy against the unstable bladder.
Endorphin mechanisms are responsible for the beneficial effects of opioid antagonists on cerebral function during relative cerebral ischaemia in rats
Authors: SKARPHEDINSSON J. O. , THOREN P.
Published: December 2008

The present study was conducted to examine the mechanisms behind the previously reported beneficial effects of high doses of naloxone on impaired cerebral function due to hypotensive haemorrhage in spontaneously hypertensive rats (SHR). The stereo‐specificity of the effects of two opioid receptor antagonists, naloxone (Nal) and Win 44.441‐3 (Win), was tested. The effects of thyrotropin releasing hormone (TRH) were also examined, because this peptide has been shown to have beneficial effects in neuronal ischaemia due to spinal injury. In addition, we were interested in seeing what effect the GABA antagonist, bicucculine (Bic), had on cerebral function during relative ischaemia, because Nal in high doses is suspected to antagonize GABA transmission. Mean arterial pressure (MAP), heart rate (HR) and somatosensory evoked potentials (SEP) were recorded in chloralose‐anaesthetized SHR. The rats were bled and MAP was rapidly lowered to 50 mmHg. This resulted in transient bradycardia and attenuated SEP. When the first SEP component had decreased to 40–50% of control, the animals were retransfused to a MAP of 60–80 mmHg, to prevent further deterioration of SEP, and maintained at the new pressure level for the rest of the experiment. Fifteen to twenty minutes later, Nal, Win, TRH or Bic was injected i.v. Both (–)Nal (5 mg kg‐1) and (–)Win (imgkg‐1) improved SEP in a stereospecific manner. (+)Naloxone or (+)Win did not affect SEP significantly. Thyrotrophin releasing hormone (2 mg kg ‐1) caused further attenuation of a late SEP component. The effects of Bic (0.15‐0.25 mg kg‐1) varied between animals but, on average, no significant effects were observed. Thus, the results strongly indicate the involvement of endogenous opioids in the pathophysiology of cerebral ischaemia and indicate beneficial effects of opioid receptor antagonists on cerebral function in this model of relative cerebral ischaemia.
Selective α2‐adrenoceptor activation by clonidine: effects on45Ca2efflux and insulin secretion from isolated rat islets
Authors: SKOGLUND G. , LUNDQUIST I. , AHRÉN B.
Published: December 2008

A possible role for Ca2+in the α‐adrenoceptor‐induced inhibition of glucose‐stimulated insulin secretion was studied in isolated rat islets by the use of the selective α2‐adrenoceptor agonist clonidine. We found that clonidine, in contrast to the a,‐adrenoceptor agonist phenylephrine, inhibited glucose‐stimulated insulin secretion at dose levels below 10‐6mol l‐1. In islets preloaded with46Ca2+and perifused at 2 mmol llCa2+, clonidine (10‐6moll‐1) reduced the glucose (13.3 mmol l‐1)‐stimulated46Ca2+efflux during both the first and second phases of insulin secretion. Furthermore, the inhibitory effect of clonidine on glucose (13.3 mmol l‐1)‐stimulated insulin secretion was partially counteracted by raising the extracellular Ca2+concentrations. Moreover, the calcium channel agonist Bay K 8644 counteracted the inhibition by clonidine on glucose‐stimulated insulin secretion. Our results suggest that selective α2‐adrenoceptor‐induced inhibition of glucose‐stimulated insulin secretion is mediated, at least partially, by restraint of Ca2+‐influx. This action might in turn be exerted through interference with the voltage‐dependent calcium channels.
The consequences of fibre heterogeneity on the force‐velocity relation of skeletal muscle
Authors: JOSEPHSON R. K. , EDMAN K. A. P.
Published: December 2008

The consequences of fibre heterogeneity on the collective force‐velocity properties of bundles of parallel fibres were examined in a simulation model. The model was tested by comparing the actual force‐velocity curve of a bundle of three fibres, each of which had been individually characterized, with the force‐velocity curve predicted by the model for the bundle based on the individual fibre properties. The predicted and measured force‐velocity curves were in excellent agreement. The curvature of the force‐velocity relation for a muscle, as indicated by a/P0 in Hill's (1938) hyperbolic equation, increases with increasing heterogeneity in the maximum shortening velocities (Vmax(1)) of the individual fibres in the muscle. In a muscle that is heterogeneous with respect to Vmax(1), the maximum shortening velocity determined by the slack test method (Vo) can be expected to represent the fastest fibre(s) in the muscle. The maximum velocity of shortening (Vm), determined by extrapolation from a hyperbola that is fitted to force‐velocity data at finite loads, is substantially lower than Vo. The difference in estimates of Vo and Vm is a function of: (i) the degree of heterogeneity of the muscle with respect to Vmax(1) and the curvature of the force‐velocity relationship of the individual fibres, and (ii) the force range used to establish the hyperbola from which Vm is derived. The ratio of Vm to VO can be used as an index to estimate the degree of variability in the maximum velocity of shortening among individual fibres in a muscle.
The effects of tenotomy and overload on the postnatal development of muscle fibre histochemistry in the cat triceps surae
Authors: GOLLVIK L. , KELLERTH J.‐O. , ULFHAKE B.
Published: December 2008

Five to seven day‐old kittens were subjected to partial tenotomy of the Achilles (triceps surae) tendon. The effects of tenotomy and overload on the development of muscle fibre histochemistry and fibre sizes were investigated when the cats had reached the adult stage. The examined muscles were the uniform soleus and the mixed medial gastrocnemius. Tenotomized muscles of both types had lower weights than their controls. Tenotomized soleus showed a redistribution of succinic dehydrogenase (SDH) activity, together with signs of muscle fibre death. Tenotomized medial gastrocnemius muscles displayed more severe degenerative signs than the soleus, together with signs of fibre death. The fibre death seemed to affect mainly fibres of type lib. Moreover, a less distinct differentiation in histochemical staining pattern between muscle fibre types was found in these muscles. Overloaded soleus muscles had greater weights than their controls, while no difference could be shown for the overloaded medial gastrocnemius. The overloaded medial gastrocnemius showed a uniform hypertrophy of all fibre types. Also, overloaded soleus showed a uniform hypertrophy. Both types of muscle showed a normal histology as well as normal staining characteristics (SDH and AcATPase). It is concluded that both soleus and medial gastrocnemius are sensitive to loss of muscle tension during development. The basic features of muscle morphology and histochemistry were normal, though, and it is suggested that other factors account for most of the normally occurring development and differentiation.
Properties of the macula densa mechanism for renin release in the dog
Authors: BUGGE J. F. , STOKKE E. S. , KIIL F.
Published: December 2008

To study the macula densa mechanism for renin release, both the macula densa and the haemodynamic mechanisms were activated in anaesthetized dogs with denervated kidneys, either by renal arterial constriction to a renal arterial pressure (RAP) of 52 ±2 mmHg or by ureteral occlusion to a ureteral pressure of 95–105 mmHg, 20–25 mmHg below RAP. Renal arterial constriction increased renin release from 0.3+0.2 to 16 + 4 μg AI min‐1. At low RAP, renin release was subsequently reduced to 7 ± 3 μ AI min‐1when sodium excretion was raised far above control values by plasma volume expansion and acetazolamide infusion. Ethacrynic acid (3 mg kg‐1body wt.) restored renin release to pre‐expansion values, and a large dose (25 mg kg‐1body wt.) prevented renin release from falling even after unclamping the artery. During ureteral occlusion with stopped glomerular filtration, plasma volume expansion, acetazolamide and ethacrynic acid infusion did not alter renin release. On the other hand, β‐adrenergic stimulation by isoproterenol raised renin release equally (by 30–40 μg AI min‐1) before and after plasma volume expansion, during both renal arterial constriction and ureteral occlusion. Indomethacin (10 mg kg‐1body wt.) abolished renin release induced by ethacrynic acid infusion and ureteral occlusion. We conclude that the macula densa mechanism for renin release is inactivated by high NaCl reabsorption during plasma volume expansion and acetazolamide infusion, reactivated by inhibition of NaCl reabsorption with ethacrynic acid and completely inhibited by indomethacin. The degree of activation does not influence the renin release induced by β ‐adrenergic stimulation.
Increased behavioural response to intrathecal substance P after intracerebroventricular 5,7‐dihydroxytryptamine but not after p‐chlorophenylalanine administration
Authors: EIDE P. K. , HOLE K. , BROCH O. J.
Published: December 2008

The behavioural response to intrathecally injected substance P (SP, 1.25 ng) was investigated in mice after lesioning of serotonergic (5‐HT) pathways by intracerebroventricular 5,7‐dihydroxytryptamine (5,7‐DHT, 80 μg base/mouse) and after 5‐HT synthesis inhibition by P‐chlorophenylalanine (PCPA, 400 mg kg“1 for 6 consecutive days). Pretreatment with 5,7‐DHT and PCPA reduced the 5‐HT level in the spinal cord to 6 and 7% of controls and the noradenaline (NA) level to 69 and 84% of controls, respectively. Intrathecally injected SP produced a response consisting of vigorous biting, licking and scratching of the caudal part of the body. The response to SP was significantly increased 5 days after injection of 5,7‐DHT, but only a non‐significant tendency towards enhancement of the response was found after 24 h. There was no change in the response to SP 24 h after the last injection of PCPA. It is suggested that 5,7‐DHT but not PCPA induces receptor supersensitivity to SP, and that reduction in spinal SP by 5,7‐DHT may be a factor in this change in receptor sensitivity.
Adenosine as a modulator of sympathetic nerve‐stimulation‐induced release of noradrenaline from the isolated rabbit heart
Authors: WENNMALM M. , FREDHOLM B. B. , HEDQVIST P.
Published: December 2008

The ability of adenosine to inhibit sympathetic nerve‐stimulation‐induced overflow of noradrenaline was studied in isolated rabbit hearts with intact sympathetic innervation. Noradrenaline in the heart effluents was measured by HPLC with electrochemical detection. The drugs used, adenosine, theophylline, and 8‐parasulphophenyltheo‐phylline, were administered via the perfusion fluid. Adenosine (1–100 μM) dose‐dependently inhibited stimulation‐evoked outflow of noradrenaline from the heart, by up to 47%: the inhibition was completely antagonized by theophylline (200μM), AND by 8‐parasulphophenyltheophylline (100 μM). Neither theophylline nor 8‐parasulpho‐phenyltheophylline didper seaffect basal or stimulation‐evoked outflow of noradrenaline. Simultaneous infusion of adenosine (100μM) AND theophylline (200 μM) significantly increased the outflow of noradrenaline during nerve stimulation, by almost 40%. No such effect was observed by adenosine (100 μM) AND 8‐parasulphophenyltheophylline (100 μM), indicating that theophylline may facilitate transmitter release by an action dissociated from purinoceptor antagonism. It is concluded that (a) adenosine inhibits depolarization‐induced liberation of sympathetic transmitter in the rabbit heart, (b) this inhibition is mediated by activation or purinoceptors, probably located on the presynaptic nerve terminals, and (c) brief periods of sympathetic stimulation in the normoxic heart does not release sufficient amounts of adenosine to cause significant inhibition of transmitter release.
The development of homeothermy in common eider ducklings (Somateria mollissima)
Authors: STEEN J. B. , GABRIELSEN G. W.
Published: December 2008

Oxygen consumption (V02), body temperature (TB) and electric muscle activity (EMG) were measured at varying ambient temperatures (TA) in common eider ducklings from the eggs pipped to 1 day after hatching. Eggs at pipping and ducklings still wet from hatching doubled their V02 at TA= 2–4 °C compared with Ta= 27 °C, but were unable to maintain constant TB. Increased EMG activity was recorded from ducklings 30 min after hatching. Artificially dried i‐h‐old ducklings maintained normal TB (39.0–40.5) for at least 90 min at TA= 2 °C. Ducklings older than 24 h maintained homeothermy even when the pelt was artificially wetted. Oxygen consumption at thermoneutrality increased about 50% from hatching to 12 h of age. The specific thermal conductance of ducklings at different ages indicates that the youngest ducklings maintain homeothermy by having a cold periphery in addition to pelt insulation and increased VQ2, while ducklings older than 12 h rely on pelt insulation and increased Vo2 only.
Effect of hypoxia on nerve‐stimulation‐induced release of noradrenaline from the rabbit heart
Authors: WENNMALM M.
Published: December 2008

The present study addressed the hypothesis that cardiac production of adenosine (ADO) and/or prostacyclin (PGI2) during hypoxia is augmented to a level sufficient to affect nerve‐stimulation‐induced release of noradrenaline (NA). Innervated rabbit hearts were perfused at high (95% O2) or low (8% O2) oxygen pressure. The effluxes of NA and purines from the heart were determined by HPLC and that of the PGI2 metabolite by radioimmunoassay. Five minutes of hypoxia elevated effluent purines (sum of ADO, inosine, and hypoxanthine) from 1.1 μM to 6.2 μM, but did not affect the outflow of NA. The ADO receptor antagonists THEO (100–200 μM) and 8PSØT (100 μM) given during hypoxia increased the evoked outflow of NA by 77% (P < 0.01) and 37% (P < 0.05), respectively. Indomethacin (30 μM, a prostaglandin synthesis inhibitor) reduced the efflux of PGI2 metabolite by 93 % but did not per se affect NA outflow during simultaneous administration of THEO, either under normoxia or hypoxia. It is concluded that ADO, but not PGI2, plays a role in reducing transmitter release during hypoxia. In addition, hypoxia leads to an enhancement of transmitter release, probably unrelated to ADO or purines. The lack of effect of hypoxia alone on evoked outflow of transmitter seems to be the result of a combination of these two processes.
Renal effects of Atriopeptin II and dopamine receptor blockade in acutely volume‐expanded rats
Authors: HANSELL P. , MICHAELSSON K. , ULFENDAHL H. R.
Published: December 2008

Studies were made of the effects of continuous intravenous infusion of a synthetic atrial natriuretic factor (ANF) or, pre‐treatment with the dopamine receptor antagonist haloperidol, on the renal response in anaesthetized rats subjected to volume expansion with an isotonic solution at 2% kg‐1body weight (wt) h‐1. A time‐control group receiving vehicle alone was studied in parallel. Measurements were compared 75 and 145 min after initiation of the volume expansion. Seventy minutes of Atriopeptin II infusion at 10 μg h‐1kg‐1body wt did not significantly alter the glomerular filtration rate [control value 1.29 ± 0.10 ml min‐1g‐1kidney wt (n ‐7, mean ± 1 SEM), experimental value 1.20 ± 0.12], but increased sodium excretion by 49% (from 2.87 ± 0.56 to 4.27 ± 0.45 μmol min‐1). The arterial blood pressure was reduced by 9%. In previous investigations we found that in the same dosage Atriopeptin II increased sodium excretion 10‐fold in euvolaemic animals. In the time‐control group (n= 7) the response was similar to that in the atrial natriuretic factor‐treated animals with the exception that the blood pressure was unaltered. Thus, glomerular filtration rate showed no statistically significant change (1.28 ± 0.06vs.1.27 ± 0.09 ml min‐1g‐1kidney wt) while the sodium excretion increased by 96% (from 2.29 ± 0.22 to 4.50 ± 0.49 μmol min‐1). In animals pretreated with haloperidol (n= 5), the natriuretic response to the volume expansion was attenuated and was about ten times below that in the time‐control group. However, sodium excretion increased from 0.25 ± 0.14 to 0.69 ± 0.34 μmol min‐1and glomerular filtration rate from 1.06 ± 0.08 to 1.64 ± 0.10 ml min‐1g‐1kidney wt. Blood pressure remained unaltered. In conclusion, the natriuretic effect of Atriopeptin II is reduced in rats subjected to volume expansion while the hypotensive effect persists. This relative natriuretic hyporesponsiveness is, presumably, partly due to the previously documented increase in release of endogenous atrial natriuretic factor caused by the volume expansion, leading to receptor occupation. Haloperidol attenuates the natriuretic response to volume expansion. In the light of our previous finding that haloperidol can block the natriuretic effect of synthetic atrial natriuretic factor, we conclude that ANF is of importance in the natriuretic response following volume expansion.
Contractile properties during development of hypertrophy of the smooth muscle in the rat portal vein
Authors: MALMQVIST U. , ARNER A.
Published: December 2008

Department of Physiology and Biophysics, University of Lund, Sweden

Structural and mechanical alterations during hypertrophy of the rat portal vein were investigated. Growth of the vessel was induced by a partial ligature of the vessel causing an increased transmural pressure. Vessel segments from animals kept with ligature for 1, 3, 5 and 7 days, were compared with vessels from sham‐operated animals. Maximal active force and vessel cross‐sectional area increased with time in the ligated group. On day 7, force and cross‐sectional area at the optimal length, were markedly increased in the ligated group (21.1 ± 1.0 mN, 0.55 ± 0.04 mm2,n= 9) compared with the control vessels (11.7 ± 1.0 mN, 0.30 ± 0.02 mm2,n= 7). Light and electron microscopy of preparations fixed at optimal length showed that the amount of smooth muscle and the cross‐sectional area of cell profiles were almost doubled in the ligated group on day 7, consistent with hypertrophy of the smooth muscle. The force per smooth muscle cell area was similar in the two groups (ligated: 132 ± 15; control: 145 ± 16 mN mm‐2,n= 4–5). The maximal shortening velocity was significantly lower in the hypertrophied group (ligated: 0.28 ± 0.02;control: 0.41 ± 0.01 optimal length s‐1,n= 6). In chemically skinned preparations, activated by maximal thiophosphorylation of the myosin light chains, force was higher in the ligated group compared to the controls but no difference in maximal shortening velocity was observed. In conclusion, the increased transmural pressure is associated with a rapid increase in the amount of smooth muscle in the portal vein. The mechanical data show that after 7 days the force generating ability of the contractile system has increased in proportion to the smooth muscle cell mass. The unaltered maximal shortening velocity in the skinned hypertrophied preparations suggests that the kinetic properties of the maximally activated contractile system are unaltered. The decreased maximal shortening velocity in the intact hypertrophied preparations may reflect alterations in the excitation‐contraction coupling.
The relation between force and intracellular pH in fatigued, single Xenopus muscle fibres
Authors: WESTERBLAD H. , LÄNNERGREN J.
Published: December 2008

Intracellular pH (pH,) has been measured before fatiguing stimulation and during recovery in single toe‐muscle fibres of Xenopus at room temperature. Liquid ion‐sensor microelectrodes were used for pH1 measurements. The pH1 measured before fatiguing stimulation was 6.93 ± 0.11 (mean ± SD, n= 9) in type 1 fibres and 6.99 ± 0.10 (n= 4) in type 2 fibres. About 1 min after tension had been suppressed to approximately 40% of the original by repeated tetanic contractions, pH, was measured again; it was then reduced to 6.34 ± 0.13 (range 6.15‐6.50) and 6.71 ± 0.17 (range 6.50‐6.85) in type 1 and type 2 fibres, respectively. The pH1 recovered at a rate of about 0.05 pH units min‐1 and was always normalized well before tension. Fibres which exhibited post‐contractile depression (PCD), a delayed force suppression during the recovery period, had similar pH1 normalization rates to those of other fibres. The large variation in pH1 values obtained in fibres fatigued to a standard tension level leads us to conlude that an intracellular acidification is not likely to be the major cause of fatigue produced by intermittent tetanic stimulation. However, an important inhibitory effect in the most acidified fibres, cannot be excluded. Furthermore, we conclude that force recovery in our experiments is controlled by factors other than pH1.
Increased IMP content in glycogen‐depleted muscle fibres during submaximal exercise in man
Authors: NORMAN B. , SOLLEVI A. , JANSSON E.
Published: December 2008

To study the relationship between glycogen depletion and IMP accumulation in different fibre types, single fibres were dissected from biopsies taken at rest and after one hour of exercise at 70% of maximal oxygen uptake. These fibres were analysed histochemically for glycogen and fibre types and pooled into classes of type I or type II fibres with low, medium or high glycogen content, in a total of six classes. These pools were analysed for ATP, ADP, AMP and IMP contents by high performance liquid chromatography. The contents of ATP, ADP and AMP at rest, and immediately after exercise, were not significantly different between the six fibre classes. The IMP content in glycogen‐depleted fibres obtained after exercise was, however, higher than in pools of glycogen‐filled fibres obtained both at rest and after exercise. In conclusion, the elevated IMP content in glycogen‐depleted but not in glycogen‐filled type I and type II muscle fibres during prolonged submaximal exercise indicates a decreased ATP regeneration rate in glycogen‐depleted fibres, which may be a factor limiting exercise duration during prolonged submaximal exercise.
Different effects of neuropeptide Y on electrically induced contractions in the longitudinal and circular smooth muscle layers of the female rabbit urethra
Authors: SJÖGREN C. , ANDERSSON K.‐E. , ANDERSSON P.‐O. , MATTIASSON A. , UVELIUS B.
Published: December 2008

The effects of neuropeptide Y (NPY) on preparations of isolated longitudinal and circular smooth muscle from rabbit urethra were studied. In both types of muscle, electrically induced contractions and relaxations could be abolished by tetrodotoxin, (TTX). In the longitudinal muscle preparations the contraction was slightly reduced by prazosin, but markedly reduced by scopolamine and NPY. The NPY effect was not influenced by pretreatment with rauwolscine. Pretreatment with NPY had no effect on contractions induced by noradrenaline (NA) or carbachol and the peptide did not relax preparations contracted by these agents. In circular muscle an initial, fast response, not sensitive to prazosin or scopolamine was occasionally observed following electrical stimulation. A slow contraction component was regularly seen; this response was abolished by prazosin. Neuropeptide Y did not influence any of these responses. The preparations were concentration‐dependently contracted by NA, whereas carbachol had no effect. Pretreatment with NPY did not affect contractions induced by NA, nor did the peptide relax NA‐contracted preparations. In neither longitudinal nor circular muscle strips did NPY affect the electrically induced TTX sensitive relaxation of NA‐contracted preparations. The results suggest that in the rabbit urethra NPY reduces contractions in the longitudinal muscle layer by selectively inhibiting the release of acetylcholine from cholinergic nerves. Neuropeptide Y did not appear to have any significant postjunctional effects nor to interfere with the release, or effects of NA or other transmitter agents. The physiological importance of the urethral effects of NPY remains to be established.
Effects of bumetanide on bile flow in the pig
Authors: GROTMOL T. , BUANES T. , SØRENSEN H. , RÆDER M. G.
Published: December 2008

This study was performed on 12 anaesthetized pigs in order to examine the effect of the ‘loop’ diuretic bumetanide (inhibitor of Na, K, Cl‐co‐transport) on ductular bile secretion. It has previously been shown that administration of furosemide (a less potent ‘loop’ diuretic) to dogs and rats increases bile flow due to inhibition of ductular reabsorption of electrolytes and water. In group I (n= 6) bumetanide (median biliary concentration: 8.4 times 10‐3mol l‐1) increased bile flow and biliary concentration of HCO3by 200% (116–320) and 50% (26–96), respectively. Biliary concentration of Cl was significantly decreased by 6% (2–12) following administration of bumetanide. In group II (n= 6) bile secretion was measured during secretin infusion (3 CU kg b. wt h‐1) in the arterial pH range of 7.40‐7.00, both before and after bumetanide administration in each animal. Bumetanide (median biliary concentration: 2.7 times 10‐3mol 1‐1) did not significantly alter biliary secretion of water, HCO3, Na, K or Cl. Bile acid secretion was reduced by 30% from 43 (28–55) to 30 (17–41) μmol mu‐1(P< 0.05) while hepatic venous concentration of bile acids was raised by 90% (54–126) from 184 (113–309) to 350 (229–502) μmol 1‐1(P< 0.05) at slightly increased hepatic blood flow. Hepatic venous serum concentration of bumetanide was 4.8 (2.1–7.4) x io‐4mol 1‐1(unbound fraction). If the choleretic effect of bumetanide was due to inhibition of an apical Na, K, Cl‐co‐transport in bile duct cells, biliary concentration of Cl would have increased rather than decreased following bumetanide administration. Further, the choleretic effect of bumetanide was abolished in the presence of secretin. It is concluded that bumetanide has a secretin‐like effect rather than inhibiting a putative Na, K, Cl‐co‐transport. Bumetanide reduced bile acid secretion by impairing hepatocellular uptake of taurocholic acid.