bluuebunny/crossref_metadata_2025 huggingface dataset:
Endogenous nitric oxide as a probable modulator of pulmonary circulation and hypoxic pressor response in vivo
Authors: PERSSON M. G. , GUSTAFSSON L. E. , WIKLUND N. P. , MONCADA S. , HEDQVIST P.
Published: December 2008

The objective of this study was to investigate the role of endogenous nitric oxide, formed from L‐arginine, in the regulation of pulmonary circulation in vivo, with special reference to the hypoxic pressor response. In artificially ventilated open‐chest rabbits, pulmonary vascular resistance at normoxic ventilation (F102= 21 %) was 78C 16 cmH2O ml‐l min 1000‐1 (mRUL). Hypoxic ventilation (F102= 10%) increased pulmonary vascular resistance to 117 ± 17 mRUL. Nw‐nitro‐L‐arginine methylester (L‐NAME), an inhibitor of nitric oxide synthase, increased pulmonary vascular resistance at normoxic ventilation to 192 ± 28 mRUL and during hypoxic ventilation to 462 ± 80 mRUL. During Nw‐nitro‐l‐arginine methylester infusion there was also an increase in mean arterial blood pressure as well as a decrease in cardiac output that was even more pronounced during hypoxic ventilation. L‐arginine reversed the effect of Nw‐nitro‐l‐arginine methylester on pulmonary vascular resistance at normoxic ventilation to 140 ± 26 mRUL and at hypoxic ventilation to 239 ± 42 mRUL.

In spontaneously breathing closed‐chest rabbits, Nw‐nitro‐L‐arginine methylester evoked a marked decrease in arterial Po2, and increases in respiration frequency and central venous pressure, while blood pH, PCO2 and base excess remained unchanged. Taken together these findings indicate that endogenous nitric oxide, formed from L‐arginine, might be a regulator of ventilation‐perfusion matching at normoxic ventilation, and that nitric oxide acts as an endogenous modulator of the hypoxic pressor response.
Neurotransmitters and pre‐ and post‐junctional receptors involved in the vasoconstrictor response to sympathetic nerve stimulation in rat tail artery
Authors: BAO J. X. , ERIKSSON I. E. , STJÄRNE L.
Published: December 2008

The study was prompted by the need to re‐evaluate, in view of the complexity of the evidence in the literature, the relative roles of different sympathetic transmitters and receptors in the contractile response of the tail artery of adult normotensive rats to electrical field stimulation. By the pharmacological approach employed, noradrenaline and adenosine 5′‐triphosphate appeared to contribute to this response; the possible roles of other putative transmitters such as neuropeptide Y could not be examined due to lack of specific antagonists. Noradrenaline, clearly the main mediator, exerted both excitatory and inhibitory effects, acting in part via different receptors depending on the stimulus parameters. Thus, yohimbine and prazosin (α2‐and α1‐adrenoceptor antagonists, respectively) were about equally effective as inhibitors of the noradrenaline‐mediated contractile response to stimulation with short trains and/or at low frequency, but the response caused by long trains and/or high‐frequency stimulation was much more strongly inhibited by prazosin than by yohimbine. As expected, yohimbine enhanced the [3H]noradrenaline overflow response to long but not to short stimulus trains, presumably because in the latter case the noradrenaline concentration in the relevant biophase was too low to activate the pre‐junctional α2‐adrenoceptors. Finally, propranolol, an unselective β‐adrenoceptor antagonist, enhanced the neurogenic contraction, indicating that noradrenaline restricts this response by effects via post‐junctional β‐adrenoceptors. Adenosine triphosphate appeared to exert dual, excitatory as well as inhibitory, post‐junctional effects. Thus, the P2X‐purinoceptor desensitizing agent, α, β‐methylene adenosine triphosphate, abolished the initial phase, but enhanced the amplitude of the neurogenic contraction, without affecting the nerve stimulation‐induced overflow of [3H]noradrenaline. The results indicate that noradrenaline and adenosine triphosphate, the main mediators of the neurogenic contraction of this preparation, act in a more complex fashion than earlier thought; they argue against a significant direct contribution by other putative transmitters but do not exclude that such agents may act indirectly as modulators of this response.
Evidence from lack of decentralization‐induced supersensitivity that β2‐ adrenoceptors of the cat nictitating membrane are non‐innervated
Authors: BROADLEY K. J.
Published: December 2008

The right superior cervical sympathetic trunk of cats was sectioned preganglionically under anaesthesia. Six days later the blood pressure, heart rate and contractions of the left (control) and right (decentralized) nictitating membranes were recorded under chloralose anaesthesia (80 mg kg‐1). The α‐adrenoceptor‐mediated contractile responses of the nictitating membrane to intravenous adrenaline were greater on the decentralized side than the control side, with a significant shift of the doseresponse curve to the left. After phentolamine (8 mg kg‐1i.v.), adrenaline administered intra‐arterially exerted β‐adrenoceptor‐mediated relaxation of the nictitating membranes. However, there was no difference in the sensitivity or magnitude of responses between decentralized and control sides.

In a separate series of experiments, the α‐adrenoceptor‐mediated contractile responses of the nictitating membrane to intra‐arterial noradrenaline displayed supersensitivity on the decentralized side, the dose‐response curve being significantly shifted to the left. In the same animals, the β‐adrenoceptor‐mediated relaxation responses to intra‐arterial isoprenaline were non‐significantly greater on the decentralized side, presumably because of raised tone. However, when expressed as a percentage of the maximum relaxation, there was no difference in sensitivity. This study shows that the α‐adrenoceptor‐mediated contractile response of the nictitating membrane displays supersensitivity after preganglionic section of the sympathetic innervation. This is presumably because of an up‐regulation arising from loss of sympathetic traffic onto the receptor. The relaxation response is mediated via adrenoceptors of the β2‐ subtype and shows no supersensitivity. This suggests that these receptors are not under the influence of the sympathetic innervation.
Effects of intrathecal substance P and a substance P antagonist on a reflex to noxious heat are independent of changes in tail skin temperature
Authors: EIDE P. K.
Published: December 2008

Substance P or the substance P receptor antagonist (d‐Arg1, d‐Trp7, 9, Leu11)‐substance P (Spantide) was injected into the lumbar subarachnoid space in mice, and the ability to change the tail‐flick reflex and the tail skin temperature was investigated. Tail‐flick latency (the time needed to evoke the tail‐flick reflex by noxious radiant heat) was reduced for 1–4 min after intrathecal administration of substance P (5 μg), but the tail skin temperature was not significantly changed. Nor was the tail skin temperature significantly changed after intrathecal injection of Spantide (5 pg), but this compound significantly increased tail‐flick latencies 5–30 min after injection. Analysis of co‐variance showed that the effects of substance P or Spantide on tail‐flick latency were significant, whereas the influence of tail skin temperature on tail‐flick latency was nonsignificant. Thus, intrathecal substance P induces a short‐lasting increase in nociceptive sensitivity, and intrathecal Spantide produces an antinociceptive effect of longer duration. The results seem not to be the result of changes in tail skin temperature.
Is there an intestinal natriuretic factor?*
Authors: LUNDGREN O. , HANSSON G. C.
Published: December 2008

Intestinal tissue from cats was homogenized and fractionated by ultrafiltration to a molecular range of about 500‐10,000 and separated by gel chromatography. The fractions from the gel filtrations were tested with regard to their ability to inhibit Na,K‐ATPase as assayed with ρ‐nitrophenylphosphate. The fractions that inhibited Na,K‐ATPase were pooled and named pooled fraction 2. Pooled fraction 1 contained molecules larger, and pooled fraction 3 and 4 the molecules smaller, than pooled fraction 2. The four fractions were assayed for natriuretic ‘activity’ on anaesthetized rats. Administering pooled fraction 3 (no Na,K‐ATPase‐inhibiting activity) i.v. augmented renal excretion of sodium and water, whereas the other pooled fractions did not exhibit any consistent natriuretic effect. Cardiac ventricular tissue from cats was fractionated in the same manner as was done for the intestine. None of the cardiac fractions contained any natriuretic material. It is proposed that the cat small intestine contains a natriuretic factor.
Gentamicin inhibition of Na+, K+‐ATPase in rat kidney cells
Authors: FUKUDA Y. , MALMBORG A.‐S. , APERIA A.
Published: December 2008

Na,K+‐ATPase activity is decreased in homogenized renal tissue from GM‐treated rats. This study examines whether the site of the active effect of GM on Na,K‐ATPase activity in the kidney can be localized to the proximal convoluted tubules (PCT) where the drug is taken up and where it will produce necrosis.

In rats treated with gentamicin (50 μg. kg‐1.day‐1i.m.) for 7 days, PCT Na,K‐ATPase activity was reduced as compared to vehicle‐treated rats but returned to control levels 7 days after treatment withdrawal. In another nephron segment, the medullary thick ascending limb of Henle (mTAL), where GM induced lesions are uncommon, Na,K‐ATPase activity was the same in GM‐ and vehicle‐treated rats treatment. To study thein vitroeffect of GM, dissected PCT and mTAL segments from untreated rats were preincubated for 30 min with GM 10‐3m, a dose similar to the tissue concentration in chronically treated rats. In tubule segments that were permeabilized to allow the drug to enter the cells, GM 10‐3msignificantly inhibited Na,K‐ATPase activity both in PCT and mTAL. In non‐permeabilized mTAL segments GM did not inhibit Na,K‐ATPase activity. GM inhibition of Na,K‐ATPase activity in permeabilized PCT segments persisted after the tubules were rinsed in GM free medium. GM does not inhibit Na,K‐ATPase partly purified from the renal cortex. Conclusion. Gentamicin inhibits Na,K‐ATPase activity in renal tubule cells when it has access to the cytoplasm. Treatment with GM will therefore cause a selective inhibition of Na,K‐ATPase in the proximal tubule cells.
Changes in pitutary‐adrenal activity regulate the central vasodepressor responses induced by neuropeptide Y and adrenaline in the awake unrestrained male rat
Authors: AGUIRRE J. A. , FUXE K. , ANDBJER B. , ENEROTH P. , AGNATI L. F.
Published: December 2008

The central cardiovascular responses induced by neuropeptide Y (0.25 nmol) and adrenaline (2.00 nmol) given i.c.v. in close to maximal doses in the awake, unrestrained male rat were studied following changes in the pituitary‐adrenal activity. Adrenalectomy (1 week) alone significantly reduced the vasodepressor response to i.c.v. adrenaline but not to i.c.v. neuropeptide Y. Corticosterone replacement treatment (5 mg kg‐1x 2, i.p., 1 week) significantly reduced both the maximal (peak) and overall (area) vasodepressor responses to i.c.v. adrenaline and neuropeptide Y (only overall responses) in the adrenalectomized rat. Corticosterone treatment alone in the sham‐operated rat highly significantly reduced the vasodepressor responses to both i.c.v. adrenaline and neuropeptide Y. The bradycardic action of centrally administered neuropeptide Y was no longer significant after alterations in pituitary‐adrenal activity.

The present results suggest that corticosterone treatment can abolish the centrally evoked vasodepressor responses to close to maximal doses of adrenaline and neuropeptide Y, which may contribute to their hypertensive properties in man. Finally, after adrenalectomy the central vasodepressor responses to neuropeptide Y dominate, since the adrenergic vasodepressor responses are selectively reduced. This dominance is reduced by corticosterone replacement treatment. The results indicate an antagonistic role of adrenocortical steroids in control of centrally induced acute vasodepressor responses to neuropeptide Y and adrenaline.
Characterization of contraction‐mediating prostanoid receptors in human hand veins: effects of the thromboxane receptor antagonists BM13, 505 and AH23848
Authors: ARNER M. , HÖGESTÄTT E. D. , USKI T. K.
Published: December 2008

The effects of prostaglandin F2α, prostaglandin E1, prostaglandin E2and the thromboxane A2analogue U46619 were determined in ring segments of human hand veins. All prostanoids except prostaglandin E1elicited contraction. The order of potency was U46619 > prostaglandin F2α> prostaglandin E2. The thromboxane receptor antagonists BM13, 505 and AH23848 both caused a parallel rightward displacement of the concentration‐response curve for U46619 without depression of the maximum contraction, suggesting competitive antagonism. Schild plots for both antagonists yielded regression lines with slope indices not significantly different from unity. The pA2values for BM13, 505 and AH23848 were 7.9 and 8.4 respectively. Both antagonists also effectively inhibited prostaglandin F2α‐induced contractions. However, AH23848 significantly reduced the maximum response, and the results with BM13, 505 gave no clear indication of the type of inhibition. In vein segments submaximally contracted by 5‐hydroxytryptamine, prostaglandins E1and E2produced a biphasic response with a relaxation at low and a contraction at high concentrations. Prostaglandin F2αand U46619 failed to elicit relaxation under these conditions. However, in the presence of either thromboxane receptor antagonist, prostaglandin F2αbut not U46619 produced a relaxation. The results are compatible with the presence of at least two prostanoid receptors in human hand veins, a contraction‐mediating thromboxane receptor and an as yet unclassified receptor eliciting relaxation. U46619 was a potent agonist at the thromboxane receptor and prostaglandin E1and E2preferentially stimulated the relaxation‐mediating receptor, whereas prostaglandin F2αappeared to be active at both receptor sites.
Effect of training on central factors in fatigue following two‐ and one‐leg static exercise in man
Authors: RUBE N. , SECHER N. H.
Published: December 2008

Leg strength and fatigue developed during 150 repeated two‐ and one‐leg isometric maximal voluntary contractions were determined before and after a 5‐week one‐ (n = 6) or two‐ (n = 7) leg training programme including a control group of five subjects. Two‐ and one‐leg training increased two‐ and one‐leg strength by 59 (range 8–107) and 36% (–1–69) respectively (P < 0.01) with no significant difference between the two groups. Two‐leg training decreased (P < 0.05) fatigue only during two‐leg maximal voluntary contractions (from 20 [11–26] to 13% [6–27]); and one‐leg training fatigue only during one‐leg maximal voluntary contractions (from 20 [15–23] to 11% [9–24]) despite the fact that both legs were trained. Surface electromyographic activity decreased during both repeated two‐ and one‐leg maximal voluntary contractions (P < 0.01) but a reduction in electromyographic decay was seen (P < 0.05) during two‐leg maximal voluntary contractions after two‐leg training. Training increased fast‐twitch b fibre size (P < 0.01), and glycogen depletion was seen in fast‐twitch (a and b) fibres, but the relative fast‐twitch b area did not increase significantly. No training effects were seen in the control group. The results show that an approximately 47% increase in muscle strength may take place without a significant change in the relative percentage of muscle fibre types or in the average muscle fibre size. Furthermore, the specificity of the training response to fatigue developed during repeated two‐ and one‐leg maximal voluntary contractions suggests a change in the nervous influence on the motor units.
Metabolic correlates to pacemaker activity in the smooth muscle of guinea‐pig mesotubarium
Authors: LYDRUP M.‐L. , HELLSTRAND P.
Published: December 2008

Oxygen consumption (Jo2) and lactate production (Jo1ac) were measured during spontaneous activity in the guinea‐pig mesotubarium. During spontaneous contractions Jo2 increased to maximally 0.270±0.025 μmol min‐1 g‐1 (n= 23), followed by a rapid immediately upon relaxation. In the relaxed period (5–15 min) between spontaneous contractions Jo2M/sb> continued to slowly decrease by about 25% towards a final value of 0, 150±0.01 μmol min‐1 g‐1. J1ac showed no consistent variation during the relaxed period. Ouabian (10‐6 M) produced a contracture, which was abolished by the Ca2+‐antagonist felodipine (10‐6 M). In the presence of felodipine, addition of oabian caused depolarization and a decrease of oxygen consumption by 21% and of lactate production by 31%. Exchange of glucose in the Physiological Krebs solution for β‐hydroxybutyrate did not influence spontaneuous activity, while subsequent addition of cyanide (2mM) abolishd contractions and caused a hyperpolarization of 15 mV. Blockade of ATP‐dependent K+ channels by addition of glibenclamide (10‐7 M) to the relaxed muscle in this situation caused spontaneous contractile activity to reappear. In glucose‐containing Krebs solution glibenclamide had no effect on the sponstaneous contractile and electrical activity and contractions persisted after addition of cyanide. The relaxing and hyperpolarizing effect of pinacidil could be counteracted by addition of glibenclamide. The result suggest that a decrease in electrogenic Na+/K+‐pump activity in the course of the relaxed period between contractions could contribute to the pacemaker behaviour. ATP‐dependent K+ channels, while having little influence on the spontaneous contractile activity under normal metabolic conditions, could be activated during blockade of aerobic and anaerobic metabolism, leading to inhibition of pacemaker activity.
Compartment analysis of vascular effects of neuropeptides an capsaicin in the pig nasal mucosa
Authors: STJÄRNE P. , LACROIX J. S. , ÄNGGÅRD A. , LUNDBERG J. M.
Published: December 2008

The vascular effects of local infusion of capsaicin, substance P (SP), calcitonin generelated peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were monitored in an experimental model on the pig nasal mucosa. Arterial, venous and superficial mucosal blood flow (laser‐Doppler flowmetry) as well as mucosal volume, reflecting changes in capacitance vessels were studied in parallel. All substances induced concentration dependent increases in the parameters studied with the exception of the decrease in the superficial mucosal flow induced by vasoactive intestinal polypeptide. This latter finding was interpreted as a stealing phenomenon and suggests that vasoactive intestinal polypeptide mainly exerts its vasodilatory effect in the deeper glandular layers of the nasal mucosa. The vasodilatory effect of capsaicin, except the laser‐Doppler signal, was markedly reduced by pretreatment with a combination of the ganglionic blocking agent chlorisondamine and atropine implying that capsaicin evokes a central reflex with a final parasympathetic pathway and release of agents like vasoactive intestinal polypeptide. The remaining capsaicin response may depend on a local effect with axon reflexes and the release of sensory neuropeptides with actions on superficial mucosal blood flow.
Effects of calcium supplementation and deoxycorticosterone on plasma atrial natriuretic peptide and electrolyte excretion in spontaneously hypertensive rats
Authors: PÖRSTI I. , WUORELA H. , ARVOLA P. , MÄMMI P. , NURMI A.‐K. , KOISTINAHO J. , LAIPPALA P. , VAPAATALO H.
Published: December 2008

The effects of calcium and the mineralocorticoid deoxycorticosterone (DOC) on blood pressure were studied in four groups of spontaneously hypertensive rats (SHR): (1) control; (2) calcium; (3) deoxycorticosterone and; (4) deoxycorticosterone + calcium. Calcium was given as 1.5% calcium chloride in drinking fluid and deoxycorticosterone by weekly subcutaneous injections (25 mg kg‐1). During the nine weeks of treatment the increase in systolic blood pressure was enhanced in the deoxycorticosterone and attenuated in the calcium group, whereas the deoxycorticosterone + calcium group did not deviate from control. Total plasma calcium was elevated in the calcium group. Plasma concentrations of sodium and atrial natriuretic peptide (ANP) were increased by deoxycorticosterone while neither of the calcium‐treated groups differed from control in these respects. Urinary excretions of calcium and sodium were increased in both groups receiving calcium, and also the deoxycorticosterone group excreted more calcium into urine than the control. Adrenergic nerve density in a section of the mesenteric artery and the urinary excretion of noradrenaline and adrenaline were similar in all study groups. The results indicate that calcium supplementation can attenuate the development of hypertension and prevent the deoxycorticosterone‐induced blood pressure rise in SHR, possibly by influencing sodium metabolism as seen in increased natriuresis, and by preventing the actions of deoxycorticosterone on sodium balance.
Protective role of sympathetic nerve activity to exercising skeletal muscle in the regulation of capillary pressure and fluid filtration
Authors: MASPERS M. , EKELUND U. , BJÖRNBERG J. , MELLANDER S.
Published: December 2008

This study describes the integrated sympathetic/metabolic control of capillary pressure (Pc) and filtration in cat skeletal muscle as studied during graded exercise and superimposed graded (2, 6 and 16 Hz) vasoconstrictor nerve excitation. The applied technique permitted simultaneous analysis of the underlying changes of resistance in the whole vascular bed (RT) and in its large‐bore arterial resistance vessels (> 25 μm), small arterioles (< 25 μm) and veins. Graded exerciseper secaused graded increases in capillary pressure, which at heavy work exceeded the resting control value by 12.2 mmHg, in turn leading to marked loss of plasma fluid by filtration. Sympathetic nerve stimulation was much more efficient in lowering capillary pressure during exercise than at rest, in spite of an exercise‐induced marked attenuation of the vasoconstrictor response (RT). The sympathetically evoked capillary pressure fall per unit resistance increase was larger the greater the degree of exercise vasodilatation, implying a highly nonlinear relation between capillary pressure and RTand also between the more direct determinant of capillary pressure the post‐ to precapillary resistance ratio, and RT. Strenuous exercisein vivois known to be associated with a markedly increased reflex sympathetic discharge to exercising muscle which has been a puzzling feature in view of its untoward restriction of the exercise hyperaemia response. To the extent the present results are representative for thisin vivosituation, they suggest that sympathetic discharge to exercising muscle, in spite of some flow restricting effect, might serve a highly beneficial function, causing effective protection against excessive work‐induced rise of capillary pressure and harmful plasma fluid loss into the extravascular space of working muscle.
Lactate transport in skeletal muscle cells: uptake in L6 myoblasts
Authors: BEAUDRY M. , DUVALLET A. , THIEULART L. , ABIDA K. EL , RIEU M.
Published: December 2008

During exercise, lactate is produced by degradation of glucose‐6‐phosphate during glycolysis in the contracting muscles. This lactate is metabolized during and after exercise in the muscle itself and also in the liver and other muscles, which can use it as an energy metabolite or can resynthetize glycogen. Lactate is transported in the blood, and the rate of muscular utilization may be limited by two factors: the rate of metabolic utilization by the muscle cell; and the rate of transport across the membrane regulating lactate transfer from the blood to the cell. We have studied lactate uptake in L6 muscle cells by incorporation of 14C‐lactate. The uptake rates were linear for 20 seconds with 5 mM lactate and 10 seconds with 20 mM. The uptake during 10 seconds for physiological lactate concentrations (1–20 mM) gave a straight line passing through the origin. Lactate uptake was not altered by specific inhibitors of lactate transport (2.5 mM α cyano‐4‐hydroxycinnamic acid. 5 μM 4, 4′‐diisothiocyanostilbene‐2, 2'disulphonic acid) or by the stereospecific D‐lactate inhibitor. The results suggest that L‐lactate uptake in L6 cells occurs by passive diffusion.
The axonal transport motor ‘kinesin’ is bound to anterogradely transported organelles: quantitative cytofluorimetric studies of fast axonal transport in the rat
Authors: DAHLSTRÖM A. B. , PFISTER K. K. , BRADY S. T.
Published: December 2008

Monoclonal antibodies to the axonal transport ATPase kinesin were used in an immunofluorescent study on mammalian nerves. Following crushing of the sciatic nerve and the ventral roots of adult rats, immunoreactive material was found to accumulate rapidly, mainly proximal to a crush but also, to some degree, distal to a crush. The strongest immunofluorescence was observed after incubation with the H2 antibody against the heavy subunit of kinesin. Using the cytofluorimetric scanning (CFS) procedure, the accumulated amounts were quantified and it was found that the retrogradely accumulating kinesin‐like immunoreactivity (IR) was about 4–12% of the anterogradely transported kinesin‐IR. The results were compared to the vesicle marker p38 (synaptophysin), which was found to accumulate to a significant extent on both sides of the crush. Cytofluorimetric scanning measurements indicated that nearly 50% of the anterogradely accumulated p38–IR was recycling to the cell body. The results demonstrate that kinesin in the living axon is affiliated with anterogradely transported organelles. Retrogradely transported organelles appeared to carry very little kinesin‐IR, suggesting that kinesin may be subject to turnover, distinct from that of p38, in the distal regions of the axon.
The contribution of ultrafiltration pressure for glomerular hyperfiltration in young nephrectomized rats
Authors: CELSI G. , SAVIN V. J. , HENTER J. I. , SOHTELL M.
Published: December 2008

Ablation of renal tissue in infancy is followed by increased ultrafiltration pressure, enlarged filtering area and decreased hydraulic conductivity of the glomerular capillaries. This study examines the effect of a calcium channel blocker, felodipine, on ultrafiltration pressure and renal function in rats uni‐nephrectomized at 5 days of age. The rats were treated with felodipine from 24 to 60 days of age or left untreated. Sham‐operated untreated rats were used as controls. Arterial blood pressure levels were similar in the three groups of rats. Glomerular filtration rate and renal plasma flow in the left kidney were significantly higher in treated and untreated rats than in sham‐operated untreated rats; significantly higher values were also found in treated than in untreated rats. Single nephron glomerular filtration rate was significantly higher in treated and in untreated than in sham‐operated untreated rats, but was not different in treated and untreated rats. Ultrafiltration pressure was significantly higher in untreated rats than in treated and in sham‐operated untreated rats; no difference was found between treated and sham‐operated untreated rats. Ultrafiltration coefficient (Kf) was significantly higher in treated rats than in untreated and sham‐operated untreated rats. Hydrolic conductivity of the glomerular capillaries was significantly lower in untreated than in treated and in sham‐operated rats, but was not different in treated and sham‐operated rats. Glomerular volume was higher in treated and untreated rats than in sham‐operated rats. Conclusion: high ultrafiltration pressure is not an absolute requirement for the hyperfiltration that follows infant nephrectomy.
Relaxation of sheep urethral muscle induced by electrical stimulation of nerves: involvement of nitric oxide
Authors: Garcia‐Pascual A. , Costa G. , Garcia‐Sacristan A. , Andersson K.‐E.
Published: December 2008

Isolated smooth muscle preparations from the sheep urethra responded to electrical field stimulation with contraction when basal tension was low (5–6 mN), but with relaxation when the preparations were contracted with noradrenaline (NA), clonidine, or prostaglandin F2α. No relaxant response could be elicited in high K+ (124 mM) contracted preparations. Electrically induced relaxations had a threshold of less than 1 Hz and a maximum at 8 Hz. Both contractant and relaxant responses were abolished by tetrodotoxin, indicating that they were caused by transmitters released from nerves.

The amplitude of the relaxant responses showed a highly significant correlation to the tension induced by noradrenaline. A coefficient (R/T) was calculated relating relaxation to noradrenaline‐induced tension. In this way it is possible to separate the effect of drugs on muscle tension (non‐specific effect) from their action on the electrically induced relaxation (specific effect). Chemical sympathectomy with 6‐OHDA did not significantly modify the relaxant response to 6 Hz in noradrenaline contracted strips, as evaluated by the R/T coefficient. The electrically induced relaxation was not affected by hexamethonium, propranolol, phentolamine, muscarinic receptor blockade, cocaine, indomethacin, or methysergide. Both nifedipine and Bay K 8644 inhibited significantly the response induced by electrical stimulation, decreasing its maximum. Nifedipine, but not Bay K 8644, significantly reduced the level of tension induced by noradrenaline, and its effect, evaluated by the R/T coefficient, was an increase in the electrically induced relaxation, whereas Bay K 8644 had a significant inhibitory effect. Pre‐treatment with NG‐nitro‐L‐arginine (L‐NOARG) for 30 minutes did not significantly change resting tension, but concentration‐dependently reduced the relaxant responses, and at the highest L‐NOARG concentration used, relaxation was changed into a contraction. NO (present in acidified solution of NaNO2) still produced relaxation. NG‐nitro‐D‐arginine (D‐NOARG) had no effects.

It is suggested that in contracted sheep urethral muscle, the relaxation produced by electrical stimulation of nerves is mediated by NO.
Effect of felodipine on the myogenic response to dynamic stretch in vascular smooth muscle
Authors: Bülow A. , Johansson B.
Published: December 2008

In the present experiments we examined the effect of felodipine, a vasoselective dihydropyridine calcium antagonist, on contractile responses to dynamic and static stretch of the isolated portal vein of the rat. Dynamic stretch was applied to the vascular smooth muscle at graded rates (from 0.5‐1.5% muscle length s‐1). Earlier observations (Johansson & Mellander 1975) of a rate‐dependent excitation of the vascular smooth muscle by dynamic stretch were confirmed. Addition of felodipine, 3 nM, reduced the spontaneous activity at static lengths to about 50% but resulted in much stronger inhibition of the dynamic stretch responses. Particularly the rate‐dependent increase in active force was no longer evident since the response at high rates of passive lengthening was most clearly reduced by felodipine.

By contrast, lowering of the extracellular Ca2+concentration resulted in a comparable attenuation of the spontaneous contractile activity and of the dynamic stretch responses which still showed the typical rate dependence. Therefore, the pronounced inhibition by felodipine of the dynamic myogenic reactivity of the rat portal vein appeared to be a specific effect and not simply related to the overall reduction in contractile activity. We suggest that felodipine, in addition to its inhibition of action potentials and excitation‐contraction coupling may exert a special negative influence on the mechano‐electrical coupling, i.e. the process that couples dynamic stretch of the vascular smooth muscle to membrane excitation.
The adenosine analogue R‐PIA interacts with substance P binding in rat brain and spinal cord
Authors: Stiller C.‐O. , Fastbom J. , Fredholm B. B. , Brodin E.
Published: December 2008

The adenosine analogue R‐PIA interacts with substance P binding in rat brain and spinal cord
The effect of meal size on postprandial increase in cardiac output
Authors: WAALER B. A. , ERIKSEN M. , TOSKA K.
Published: December 2008

Heart rate, stroke volume, cardiac output and mean arterial blood pressure were followed from the resting primal situation and for 2 hours after intake of standardized meals in four healthy individuals. Continuous records of stroke volume and cardiac output were achieved with an improved method of Doppler ultrasonography. A smallish meal and one 2 1/2 times larger were both given twice and in random order to each of the four test persons.

The consumption of a meal invariably resulted in a cardiac output increase, which developed gradually to reach a maximum level 30 to 60 min after end of the meal. The postprandial cardiac output increase resulted from significant increases in both heart rate and stroke volume.

There were distinct and significant differences between the circulatory responses to small and large meals. The increase in cardiac output after a large meal was considerably larger and lasted for longer than the increase after a small meal. Two hours after a small meal cardiac output was nearly or fully back to pre‐meal values, while cardiac output was still markedly elevated 2 hours after a large meal. Consequently, the total ‘extra’ amount of blood delivered by the heart over 2 post‐meal hours was significantly — about 100%— larger after the large meal than after the small one.

Mean arterial blood pressure either fell or remained almost unchanged in the hour after a meal, so that total peripheral resistance was consistently and significantly reduced in the postprandial period — and considerably more so after a large meal than after a small one.
Pulmonary vascular pressure profile in adult ferrets: measurements in vivo and in isolated lungs
Authors: RAJ J. USHA , KAAPA P. , HILLYARD R. , ANDERSON J.
Published: December 2008

We have determined the vascular pressure profile in lungs of adult ferrets utilizing an anaesthetized open chested preparation and have compared the pressure profile in vivo with that in isolated, perfused lungs. Ten adult ferrets, mean body weight 980 ± 108 g, were studied. For in vivo measurements, five ferrets were anaesthetized, mechanically ventilated and the left chest wall resected. Pressures were measured in the pulmonary artery, left atrium and by micropuncture, in 20–50 μm diameter subpleural arterioles and venules. During micropuncture, ventilation was stopped for 1–2 min and the lungs kept distended at an airway pressure of 6 cmH2O. Left atrial pressure was raised to ˜ 8 cmH2O with saline infusion so that lungs were in Zone 3. Cardiac output was measured by thermodilution. Lungs of five other ferrets were isolated and perfused with a steady flow roller pump. In these lungs blood flow was adjusted so that pulmonary artery pressure was similar to that in anaesthetized ferrets, with airway and left atrial pressures at 6 and 8 cmH2O respectively (Zone 3). Blood haematocrit (35 ± 7%) was similar in the two groups. In lungs of anaesthetized ferrets total arteriovenous pressure drop was 12.l ± 1.9 cmH2O, with cardiac output being 210 ± 80 ml kg body weight‐1 min‐1. Fractional resistance in arteries was 37%, 37% in microvessels and 26% in veins. In isolated ferret lungs, though blood flow was only 48 ± 10 ml kg body wt‐1 min‐1 for the same total arteriovenous pressure drop as in vivo, the longitudinal distribution of vascular resistance was similar to that in live ferrets. We conclude that in the ferret, the contribution of arteries, microvessels and veins to total vascular resistance is similar in isolated lungs and lungs in vivo.
Localization of severa G‐protein subunits to the apical and basolateral membranes of cortical tubular cells from the rat kidney
Authors: VAN DER PLOEG I. , FREDHOLM B. B. , CARLQUIST M. , BERTORELLO A. , APERIA A. , CELSI G.
Published: December 2008

Dopamine was shown to affect Na+, K+‐ATPase activity in basolateral membranes of the rat kidney via a pertussis toxin dependent mechanism. In order to examine if some form of pertussis toxin sensitive G‐protein is present exclusively in the basolateral membrane of the rat renal cortex we examined the G‐protein composition of both apical and basolateral membrane vesicles. Western blots showed an essentially uniform distribution of Gαtotal,Gαsand Gβ over the two membranes. Gocould not be detected with western blot technique in the vesicle preparations. By contrast, the distribution of ADP‐ribosylation with the bacterial toxins pertussis toxin and cholera toxin depended on the amount of detergent in the assay and perhaps other factors, and thus could not be used to evaluate the relative amounts of G‐protein subunits. Thus, in contrast to the situation in cultured renal cells, unequal distribution of receptor and G‐protein substrates is apparently not paralleled by an unequal distribution of the detected forms of G‐proteins under physiological conditions.
Extracellular levels of adenosine and its metabolites in the striatum of awake rats: inhibition of uptake and metabolism
Authors: BALLARÍN M. , FREDHOLM B. B. , AMBROSIO S. , MAHY N.
Published: December 2008

The level of purines in the striatum of awake, freely moving rats was studied using microdialysis. The calculated extracellular concentration of adenosine and its metabolites inosine and hypoxanthine was very high immediately after implantation of the dialysis probe but decreased within 24 h to a level which remained stable for two days. Using in vitro calibration to determine the relative recovery of the dialysis probes we estimated resting levels in the striatal extracellular space to be 40, 110 and 580 nm, respectively. Inhibition of adenosine deaminase by deoxycoformycin produced a significant 1.4‐fold increase in extracellular adenosine levels and a fall in inosine and hypoxanthine. A combination of three uptake blockers (dipyridamole, lidoflazine and nitrobenzylthioinosine), caused a 4.5‐fold increase in extracellular adenosine levels without any change in inosine or hypoxanthine levels. After uptake inhibition deoxycoformycin did not have any significant effect. The present results show that the microdialysis technique can be used to determine levels of purines in the extracellular fluid of defined brain regions in awake animals. The high levels recorded during the first several hours after implantation may be artefactually high and reflect trauma. The results also show that adenosine levels can be altered in vivo by inhibitors of adenosine transport and adenosine deaminase. The present results indicate that the physiological adenosine level in striatal extracellular space is in the range 40–460 nm.
Juxtacellular histamine concentration governs histamine release from rat peritoneal mast cells
Authors: UVNÄS B. , ÅBORG C. ‐H. , LYSSARIDES L. , DANIELSSON L. G.
Published: December 2008

Isolated rat peritoneal mast cells release histamine when superfused with isoosmotic salt or sucrose solutions. The release was ascribed by us to an intracellular ion exchange between potassium and histamine at granule sites, resulting from a flux of cytoplasmic potassium across the granules secondary to the disturbance of the ‘state of equilibrium’ at the cell surface caused by the superfusion (Uvnäset al. 1989). In the present article is shown that the histamine releasing effect is counteracted by the addition of histamine to the superfusion fluid. The inhibition is concentration‐dependent and accompanied by concomitant changes in the potassium efflux. A 50% inhibition of the histamine release requires an external histamine concentration of 40 μm and extrapolation of the equilibrium curve hints at a total inhibition at concentrations around 170 μm.

The observations are taken to indicate that reduction of the juxtacellular histamine concentration caused by the superfusion disturbs the histamine equilibrium at the mast cell surface resulting in the activation of the histamine secretory mechanism. In other words, the secretory activity of the mast cell is checked by the juxtacellular concentration of histamine. When the juxtacellular histamine is removed e.g. on isolation procedures, other experimental situations such as superfusion, or by consumptionin vivothe mast cell delivers histamine to restore the juxtacellular equilibrium.
The action of 2,3‐butanedionemonoxime on the inotropic state in guinea‐pig myocardium
Authors: MÖRNER S. E. J. N. , WOHLFART B.
Published: December 2008

Isolated papillary muscles from guinea‐pig right ventricles were used (temperature 33 °C, stimulation frequency 0.5 Hz). Isometric twitch and action potentials were recorded. Upon addition of 2, 3‐butanedionemonoxime (BDM) (2 mm) the peak twitch force was reduced from 4.17 ± 0.4 mN/mm2to 1.68 ± 0.3 mN/mm2(n =9,P< 0.001). The time course of the isometric twitch was slightly altered. Time to peak tension (TPT) was reduced by 12.0 ± 3% (n =9,P< 0.001) whereas time to half relaxation (THR) was left unaffected. The rate of rise offorce was reduced by 35 ± 3.2 mN/mm2s i.e. 46 ± 3 %. The action potential duration and amplitude was not significantly changed by the drug. The shape of the curve relating peak twitch force of an extra beat to the preceding test interval, i.e. mechanical restitution, was affected by 2 mM 2,3‐butanedionemonoxime. The curve reached its maximum faster after addition of the drug. Maximum postextrasystolic potentiation (force in response to the prepreceding test interval) was 3.2 ± 0.4 mN/mm2in 2 mm 2,3‐butanedionemonoxime and 7.6 ± 0.7 mN/mm2in control (n= 6). However the percentage potentiation was very similar in control (82%) and in presence of 2,3‐butanedionemonoxime (91%). Peak twitch force in relation to peak force of the preceding potentiated contraction during decay of postextrasystolic potentiation was analysed. There was a linear relation between the variables, the slope being 0.34 ± 0.04 in control and 0.30 ± 0.02 in 2J‐butane dionemonoxime. This suggests that the drug is without an action on the fraction of calcium recirculating within the cell. As previously suggested the negative inotropic action of BDM can be explained by an action on cross‐bridge kinetics, however the effects on the mechanical restitution curve suggests an additional action on the calcium handling by the sarcoplasmic reticulum.
Decreased insulin‐stimulated 3–0‐methylglucose transport in in vitro incubated muscle strips from type II diabetic subjects
Authors: ANDRÉASSON K. , GALUSKA D. , THÖRNE A. , SONNENFELD T. , WALLBERG‐HENRIKSSON H.
Published: December 2008

Peripheral insulin resistance in type II diabetes mellitus has been attributed to alterations in skeletal muscle glucose metabolism. However the direct dose‐response relationship between insulin and glucose transport has not yet been studied in human skeletal muscle. We investigated 3–O‐methylglucose transport in in vitro incubated skeletal muscle strips from eight healthy controls (age 61 ± 6 yrs) and six lean type II diabetic patients treated with oral antidiabetic medication (age 73 ± 3 yrs). Rectus abdominis muscle samples (˜ 1 g), obtained during elective abdominal surgery, were clamped at their resting length in vivo, whereupon strips (20–50 mg) were prepared for in vitro incubation. Measurements of high‐energy phosphates and glycogen levels revealed that the muscle strips maintained energy levels during the incubation period. Glucose transport responded to insulin in a dose‐response manner in the control group, with a 2‐fold increase following maximal stimulation. Muscle strips from the diabetic group demonstrated a marked decrease in the insulin dose‐response curve (P < 0.01), when compared to healthy muscle strips. At a maximal insulin concentration (10,000 μU × ml‐1), the response of the diabetic muscle tissue was 50% less than that of the healthy control tissue (P < 0.05). This report demonstrates a dose‐response curve for insulin stimulated 3–0‐methylglucose transport in in vitro incubated human skeletal muscle strips. Furthermore, in type II diabetic muscle, our results provide evidence for one or several defects at a postreceptor level.
Changes in plasma hypoxanthine and free radical markers during exercise in man
Authors: SAHLIN K. , EKBERG K. , CIZINSKY S.
Published: December 2008

Eight men cycled for about 6 minutes at workloads corresponding to 44 and 72% of maximal oxygen uptake and to fatigue at 98 % maximal oxygen uptake. Blood samples from a brachial artery and a femoral vein were taken at rest and during exercise. Hypoxanthine, xanthine and urate in plasma were significantly elevated at fatigue and after 10 minutes of recovery. Only hypoxanthine showed a significant arterio‐femoral venous difference. The release of hypoxanthine from the legs increased during the recovery period and was three‐fold higher 10 minutes post exercise than at the end of exercise. It is concluded that the marked increase in plasma hypoxanthine which occurs during intensive exercise originates from the working muscle whereas the transformation to xanthine and urate may occur in other tissues. Glutathione, methemoglobin and malondialdehyd (MDA) were used as plasma markers of free radicals. Total glutathione (glutathione + glutathionedisulfide) in blood and plasma increased during intensive exercise and may be indicative of free radical formation. However, MDA was not detectable in plasma during any conditions (< 0.1 μmol × I‐1 plasma) and methemo globin decreased slightly during exercise. Further studies using more specific techniques are required to determine whether the formation of free radicals is increased after brief intensive exercise.
In vitrocharacteristics of spontaneous airway tone in the guinea‐pig
Authors: LINDÉN A. , LÖFDAHL C. G. , ULLMAN A. , SKOOGH B. E.
Published: December 2008

Spontaneous airway tone has been demonstrated in the guinea‐pig and manin vitrobut little data on the magnitude and time‐course of this phenomenon is available. Moreover, the literature on possible mediators is conflicting. In the presentin vitrostudy, spontaneous airway tone (measured as spontaneous active tension) was examined in frontally‐opened guinea‐pig airway rings (n= 4–8). The examination related to magnitude, time‐course and segmental differences as well as the role of eicosanoids, acetylcholine and adrenergic mechanisms. Spontaneous active tension of considerable magnitude (approximately 40% of maximum active tension) and stability was recorded during the second hour of the experiments. An initial small segmental difference between the trachea and the main bronchus gradually decreased during the first hour of observation. Cyclooxygenase inhibition by indomethacin completely abolished the spontaneous active tension. The leukotriene antagonist FPL 55712 reduced the active tension, whereas the leukotriene antagonist L‐648,051 did not significantly affect it. Muscarinic blockade and adrenergic depletion had no effect. We conclude that the spontaneous active tension is of such a large magnitude and stability that it may play an important role in maintaining normal airway tone and that there are no pronounced segmental differences. The complete inhibition by indomethacin and the lack of effect by L‐648,051 indicate that the spontaneous airway tone is primarily maintained by prostanoids and suggest that leukotriene D4 is of minor importance. The effect of FPL 55712 was probably due to inhibition of phosphodiesterase.