Showing papers in "Acta Physiologica Scandinavica in 1982"

Pancreatic polypeptide family (APP, BPP, NPY and PYY) in relation to sympathetic vasoconstriction resistant to α-adrenoceptor blockade

Abstract: Electrical stimulation of the cat cervical sympathetic trunk caused submandibular salivary secretion and vasoconstriction simultaneously with a contraction of the nictitating membrane. Following α- and β-adrenoceptor blockade by phentolamine or phenoxybenzamine combined with propranolol, the salivary response and the nictitating membrane contraction upon sympathetic stimulation were almost abolished. A considerable vasoconstrictor response (up to 40% of control) however still remained in the submandibular gland. This yasoconstriction, which persisted after α-adrenoceptor blockade, was rather slow in onset and had a long duration without any poststimulatory hyperemia. Local intra-arterial infusions of noradrenaline caused submandibular vasoconstriction, salivary secretion and nictitating membrane contraction. The blood flow response to exogenous noradrenaline did, however, not mimic the effects of sympathetic nerve stimulation with regard to vascular escape. Whereas the vascular escape after nerve stimulation was followed by a prolonged vasoconstriction with a gradual decline, the escape after noradrenaline infusions was accompanied by a normalization of blood flow. Local intra-arterial infusions of pancreatic polypeptide (PP)-related peptides caused a slowly developing vasoconstriction with a long duration in the submandibular gland, but no salivary secretion or contraction of the nictitating membrane. The relative molar potencies as vasoconstrictory agents were about PYY: 1, neuropeptide Y (NPY): 5, avian and bovine pancreatic polypeptid 100. The vasoconstrictor effects of PP-related peptides were resistant to α-adrenoceptor blockade and present also in sympathectomized animals, suggesting a direct action on vascular smooth muscle. Combined local infusions of noradrenaline and NPY caused a vascular response in the submandibular salivary gland which was similar to that seen upon sympathetic nerve stimulation. PYY and NPY caused increase in systemic arterial blood pressure upon systemic administration which indicates general vasoconstrictor actions. This effect was accompanied by a transient bradycardia which was due to inhibition of sympathetic tone, since it was absent in animals treated with propranolol. In conclusion, the present findings illustrate the differential sensitivity to α-adrenoceptor antagonists of the submandibular vasoconstriction and salivation as well as smooth muscle contraction of the nictitating membrane induced by sympathetic nerve stimulation. This remaining vasoconstriction may be explained by release of a nonadrenergic, PP-related transmitter such as NPY which may be present together with noradrenaline in the vascular nerves. Release of an additional vasoconstrictory factor may also account for the finding that infusions of noradrenaline do not mimic the vascular effects of sympathetic nerve stimulation in vivo.

Combined effect of elastic energy and myoelectrical potentiation during stretch-shortening cycle exercise

Abstract: In addition to the utilization of muscle's elastic energy enhancement of performance in exercise involving stretch-shortening cycle might be also due to simultaneous increase of myoelectrical activity. This hypothesis was tested by examining three athletes during jumping exercise on force-platform. Vertical jumps were performed with and without preliminary counter-movement, and the jumps were called counter-movement jump (CMJ) and squatting jump (SJ), respectively. In both conditions several jumps were performed also with extra loads on the shoulders (15–220% of b. wt.). Additional droppingjumps (DJ) were executed from different heights (20–100 cm). During jumping exercise myoelectrical activity of selected muscles from the quadriceps femoris was monitored with surface electrodes. The results obtained were similar to those reported in isolated muscle and as expected, the prestretch in CMJ shifted the force-velocity curve of concentric work to the right. In two cases enhancement of performance was attributed primarily to restitution of elastic energy because myoelectrical activity was similar to that observed in SJ. In one subject increased myoelectrical activity was observed during the concentric phase of CMJ. In DJ condition the EMG activity during eccentric phase was much higher than in SJ. Therefore the high performance in this condition was attributed to both elastic energy and reflex potentiation. In eccentric work of CMJ the average force decreased with the increase of stretching speed. This phenomenon was associated with a light increase of EMG activity. The observed results emphasize that both elastic energy and reflex potentiation may operate effectively during stretch-shortening cycle activity.

Morphology and enzymatic capacity in arm and leg muscles in 78-81 year old men and women.

Abstract: Twelve men and twelve women 78-81 years of age were studied with muscle biopsies from the right vastus lateralis and biceps brachii and with measurements of isometric and isokinetic strength for knee-extention and isometric strength for elbow-flexion. Bicycle ergometry with determination of heart rate and oxygen uptake at submaximal (50 W) and "maximal" work loads was also performed. Body cell mass was estimated from measurements of total body potassium. Muscle fibre composition with respect to slow twitch (ST = type I) and fast twitch (FT = type II) fibres did not differ between the sexes and the younger subjects drawn from population studies. The mean fibre areas averaged in vastus lateralis 4.7 and 3.3 micrometers 2 X 10(3) in men and women, respectively. This is less than 10 up to 30% of values found in sedentary younger subjects. The decline dominated in FT fibres, especially FTb fibres. In contrast biceps brachii did not show any matched fibre size reduction. The number of atrophic fibres was high and so was the frequency of "enclosed" fibres and areas with type grouping (ST fibres), indicating denervation--reinnervation. Such abnormalities are rarely seen in younger ages. Correlation analysis showed that only a minor part of the reduction in body cell mass with age could be explained by a reduction in fibre areas and that a reduction with age of the number of muscle fibres of both fibre types must be assumed. Positive correlations were observed between muscle strength and mean fibre and FT fibre areas. Comparing the present findings of skeletal muscle morphology to those in younger age groups, it is apparent that during the 8th decade of life major changes do occur. The measurements of aerobic and anaerobic enzymatic activities and of muscle capillary supply showed that levels comparable to those of younger age groups are maintained. Thus, quantitative rather than qualitative changes may explain the reduction in work performance with age.

Anoxia increases potassium conductance in hippocampal nerve cells

Abstract: The effect of anoxia on nerve cell function was studied by intra- and extracellular micro-electrode recordings from the CA1 and CA3 region in guinea pig hippocampal slices. Hyperpolarization and concomitant reduction of the nerve cell input resistance was observed early during anoxia. During this period the spontaneous activity first disappeared, then the evoked activity gradually disappeared. The hyperpolarization was followed by depolarization and an absence of a measurable input resistance. All the induced changes were reversed when the slice was reoxygenated. Reversal of the electro-chemical gradient for Cl- across the nerve cell membrane did not affect the course of events during anoxia. Aminopyridines blocked the anoxic hyperpolarization and attenuated the decrease of membrane resistance, but had no effect on the later depolarization. Blockers of synaptic transmission, Mn++, Mg++- and of Na+-channels (TTX) were without effect on the nerve cell changes during anoxia. It is suggested that the reduction of nerve cell excitability in anoxia is primarily due to increased K+-conductance. Thus, the nerve cells are hyper-polarized and the input resistance reduced, causing higher threshold and reduction of synaptic potentials. The mechanism of the K+-conductance activation is unknown at present.

Lumbar back muscle activity in relation to trunk movements during locomotion in man

Abstract: The function of lumbar back muscles was studied by relating their activity patterns to trunk movements in 7 healthy adult males during normal walking (1.0-2.5 m/s) and running (2.0-7.0 m/s) on a treadmill. The movements of the trunk in the sagittal and frontal planes were recorded with a Selspot optoelectronic system using infrared light emitting diodes as markers. The electromyographic (EMG) activity from the two main portions of the lumbar erector spinae muscles (Multifidus and Longissimus) was recorded bilaterally with intramuscular wire electrodes. The angular displacements of the trunk showed regular oscillations, but their shape, magnitude and relation to the step cycle were different in the two planes (sagittal and frontal) and varied with speed and mode of progression. The EMG pattern in both muscles showed a bilateral cocontraction with two main bursts of activity per step cycle starting just before each foot was placed on the ground. Relating the EMG to the movements of the trunk indicated that the main function of the lumbar erector spinae muscles is to restrict excessive trunk movements. During walking this restricting action is most evident for movements in the frontal plane, whereas in running the lumbar back muscles mainly control the movements in the sagittal plane.

Neuromuscular function and mechanical efficiency of human leg extensor muscles during jumping exercises.

Abstract: The influence of prestretch amplitude on the mechanical efficiency was examined with 5 subjects, who performed 5 different series of vertical jumps, each of which differed with respect to the mechanics of the knee joint action during the prestretch (eccentric) phase of the contact on the floor. Electromyographic activity was recorded from the major extensor muscles during the entire work period of 1 min per series. In addition, expired air was collected during the test and recovery for determination of energy expenditure. Mechanical work was calculated from the vertical displacement of the body during the jumps. The results indicated that high net efficiency of 38.7% was observed in condition where amplitude of knee bending in eccentric phase was small. In large range motion the corresponding net efficiency was 30.1%. In jumps where no prestretching of extensor muscles occurred the net efficiency was 19.7%. The high efficiency of small amplitude jumps was characterized by low myoelectrical activity of the leg extensor muscles during the positive (concentric) work phase. In addition, the small amplitude jumps had shorter transition time in the stretch-shortening cycle, high average eccentric force and high stretching speed. Therefore the results suggest that the restitution of elastic energy, which was also related to the length change and stiffness of the muscles during stretch, plays an important role in regulating the mechanical efficiency of work.

Store and recoil of elastic energy in slow and fast types of human skeletal muscles

Abstract: Stretch-shortening cycle refers to the mechanical condition in which store and recoil of elastic energy occur in the skeletal muscle. This leads to a greater work output when compared to a simple shortening contraction. The subjects performed vertical jumps with and without preliminary counter-movement and with small and large knee angular displacement. The results indicated that those subjects who had more fast twitch (FT) fibers benefited more from the stretching phase performed with high speed and short angular displacement. The amounts of elastic energy stored in this phase were 30 and 26 N X kgBW-1, respectively, for FT and slow twitch (ST) type subjects. The recoil of elastic energy was proportional to the amount of energy storage. In large amplitude jumps where transient period between stretch and shortening is long the both types of subjects demonstrated similar amount of storage of elastic energy (17 and 16 N X kgBW-1, respectively). However, the re-use of this elastic energy was greater in ST group (24%) as compared to the FT group (17%). The results can be interpreted through differences in sarcomere crossbridge life times between fast and slow muscle fibers. The slow type muscle may be able to retain the cross-bridge attachment for a longer period of time and therefore it may utilize elastic energy better in a slow type ballistic motion.

Adenosine actions and adenosine receptors after 1 week treatment with caffeine.

Abstract: After one week treatment with caffeine (20 mg/kg ip) the number of adenosine receptors, as determined by specific binding of (3H)-L-PIA, in rat cerebral cortical membranes was increased by about 25% Cyclic AMP accumulation induced by adenosine analogues in slices of rat hippocampus was unaffected by caffeine treatment The inhibition of lipolysis in rat fat cells by 2-chloro-adenosine was similarly unaffected The potency of caffeine as an antagonist of these adenosine-receptor mediated effects was not altered by caffeine treatment It is concluded that at least some adenosine receptors are up-regulated as a consequence of prolonged caffeine treatment, but that the increase in receptor number is not related to changes in at least two effects of adenosine and caffeine

Renal function and sympathetic activity during mental stress in normotensive and spontaneously hypertensive rats.

Abstract: The aim of the present study was to explore the role of the renal sympathetic nerves in the urinary sodium excretion response to 'mental stress' in spontaneously hypertensive rats (SHR). In conscious male SHR and male Wistar Kyoto rats (WKY) urinary sodium excretion and renal function were measured both during 'rest' and during a 20 min period of 'mental stress'. Experiments were also performed on renal denervated rats. In addition, renal sympathetic activity was measured in a separate group of rats. Urinary sodium excretion, similar at rest in SHR and WKY, decreased significantly more during the stress period in SHR (-64 +/- 5%) than in WKY (-34 +/- 7%), despite a greater arterial pressure increase in SHR. Renal sympathetic nerve activity which already at rest was higher in SHR than in WKY, also increased much more in SHR during stress than in WKY. The more intense renal sympathetic activation during stress may explain the greater reduction in urinary sodium excretion in SHR, because renal denervation almost abolished this latter response. Thus, during 'mental stress' the increased renal sympathetic activity reduces urinary sodium excretion in SHR despite the pressure rise, perhaps explaining why renal denervation delays the rise in arterial pressure in young SHR. The tachycardia response in SHR gradually subsided towards the end of the stress period, while renal sympathetic activity remained elevated. This indicates that neurogenic heart rate increases if anything underestimate the extent of sympathetic activation to e.g. the renal and splanchnic regions during increased alertness.

Volume regulation of frog skin epithelium

Abstract: Previous results (MacRobbie & Ussing 1961) in combination with published values for cellular chloride concentration and for intracellular potentials show that the chloride concentration in frog skin epithelium cells is higher than predicted for equilibrium with the inside bathing solution. Both the apical and the basolateral membrane of these cells are normally almost tight to chloride, so that the maintenance of the high chloride concentration requires little work. A basolateral permeability to chloride is, however, activated by cell swelling, and the cells lose KCl. It is now shown that the KCl thus lost cannot be regained neither in the absence of sodium in the inside bath nor in the presence of furosemide. The volume regulation reactions are, however, independent of the composition of the outside bath. It is concluded that the recovery of KCl by the epithelium is due to a basolateral co-transport of NaCl from medium to cells, combined with return of Na to the medium via the Na-K pump. The co-transport mechanism thus restores the high chloride concentration of the cells, but seems to be virtually dormant unless the cells have lost chloride.

The needle biopsy technique for fibre type determination in human skeletal muscle--a methodological study.

Abstract: The fibre type composition (type I, IIA and IIB) was determined in repeated needle biopsies from the vastus lateralis muscle of 34 healthy male subjects. Repeated biopsies were taken from one leg (n = 20), and from both legs (n = 14). The variation between duplicate biopsies was 6.2% and 12.3%, with regard to % type I-fibres, respectively. Corresponding variation in % type IIA-fibres was 4.4% and 7.3%, respectively, and in % type IIB-fibres 5.0% and 7.4%, respectively. The variation in fibre type distribution within a single biopsy was 2.2-3.0% when 200 fibres were classified and counted. Increasing the number of fibres did not reduce the calculated variation to any great extent. A major reduction of the methodological error is obtained when two biopsies are taken from the same site of the muscle. The error in the technique in classifying the type I-fibres was slight; the classification between the subgroups of type II-fibres was, however, to some extent subjected to personal estimate. There was no consistent difference in fibre type composition between the right and the left leg.

Effect of diet on the utilization of blood-borne and intramuscular substrates during exercise in man

Abstract: 20 subjects were studied at rest and during a 25 min submaximal exercise (65% of VO2 max) on two occasions, the first preceded by a fat rich diet and the second by a carbohydrate rich diet. Oxygen uptake, respiratory exchange ratio (R) and arterial-femoral venous differences for glucose, lactate, beta-hydroxybutyrate and FFA (based on the fractional extraction of 3H-palmitate) were measured at rest and during exercise. Changes in intramuscular glycogen, triglyceride and lactate concentrations were determined in muscle biopsies taken before and immediately after exercise form m. quadriceps femoris. R was lower after the fat than after the carbohydrate diet and simultaneously the FFA extraction by the exercising leg was higher. The muscle triglycerides did not changes significantly during exercise after either diet. The glucose extraction was insignificantly greater after the fat diet. The glycogen reduction was numerically smaller after the fat diet, but the difference was uncertain and difficult to evaluate due to a large variation after the carbohydrate diet. However, muscle lactate accumulation and release by the exercising leg was smaller after the fat diet, indicating a slower rate of muscle glycogenolysis. It is concluded that a fat rich diet increases the relative contribution of fat to the oxidative metabolism, that this increase, to a great extent, is covered by plasma FFA and that the concomitant decrease in carbohydrate utilization concerns muscle glycogen rather than blood glucose.

Effect of frequency of growth hormone administration on longitudinal bone growth and body weight in hypophysectomized rats.

Abstract: JANSSON, J.-O., ALBERTSSON-WIKLAND, K., EDEN, S., THORNGREN, K.-G. and ISAKSSON, O.: Effect of frequency of growth hormone administration on longitudinal bone growth and body weight in hypophysectomized rats. Acta Physiol Scand 1982, 114:261–265. Received 11 May 1981. ISSN 0001–6772. Department of Physiology, University of Goteborg and Department of Orthopaedic Surgery, University of Lund, Sweden. The effect of frequency of growth hormone (GH) administration on longitudinal bone growth and body weight was studied in hypophysectomized rats. Replacement therapy with 3 different doses of human GH [(hGH) Crescormone®] was started 10–14 days after hypophysectomy and was continued for 5 days. Longitudinal bone growth, as measured by the tetracycline method, and body weight were determined during the injection period. With a daily replacement dose of 128 μg of hGH body weight gain and longitudinal bone growth were significantly higher when the hormone was injected 4 and 8 times per day compared with animals receiving the hormone in one daily injection. When the dose of hGH was 32 or 8 μg per day, longitudinal bone growth and body weight gain were more pronounced in animals receiving the hormone 2 and 4 times per day compared with animals receiving the hormone one or 8 times per day. The results of the present study demonstrate that the frequency of GH administration influence body growth. The findings suggest that the secretory pattern of GH influence the growth rate under in vivo condition.

The effect of nicotinic and muscarinic receptor blockade on cholera toxin induced intestinal secretion in rats and cats.

Abstract: The effects of hexamethonium (cholinergic nicotinic receptor antagonist) and atropine (cholinergic muscarinic receptor antagonist) on cholera toxin induced secretion were investigated in denervated segments of the small intestine of rats and cats. While there was no effect of atropine, hexamethonium markedly inhibited choleraic secretion and turned it into a net fluid absorption in many animals. This observation further strengthens our hypothesis that the enteric nervous system is involved in cholera secretion.

Alpha and beta adrenergic effects on metabolism in contracting, perfused muscle

Abstract: The role of alpha- and beta-adrenergic receptor stimulation for the effect of epinephrine on muscle glycogenolysis, glucose- and oxygen uptake and muscle performance was studied in the perfused rat hindquarter at rest and during electrical stimulation (60 contractions/min) Adrenergic stimulation was obtained by epinephrine in a physiological concentration (24 X 10(-8) M) and alpha- and beta-adrenergic blockade by 10(-5) M phentolamine and propranolol, respectively Epinephrine enhanced net glycogenolysis during contractions most markedly in slow-twitch red fibers In these fibers the effect was mediated by alpha- as well as by beta-adrenergic stimulation, the latter involving production of cAMP, phosphorylase activation and synthase inactivation In contrast, in fast-twitch fibers only beta-adrenergic mechanisms were involved in the glycogenolytic effect of epinephrine Moreover, inactivation of synthase was less in these fibers Epinephrine also increased the net release of lactate from the hindquarter, an effect abolished by combined alpha- and beta-adrenergic blockade but by neither alpha- nor beta-adrenergic blockade alone Epinephrine increased uptake of oxygen and glucose by stimulation of alpha-adrenergic receptors and had a positive inotropic effect during contractions which was abolished by alpha- as well as by beta-adrenergic blockade The results indicate that epinephrine has profound effects on contracting muscle, and that these effects are elicited through different combinations of alpha- and beta-adrenergic receptor stimulation

Blood‐brain barrier permeability and immobilization stress

Abstract: The regional capacity of the blood-brain barrier (BBB) has been investigated in rat brain during normal conditions and after acute immobilization (IMO). The BBB function was monitored by fluorescence microscopical localization of systemically administered vital dye (trypan blue) and by studying the ability of the brain capillaries to decarboxylate and trap injected L-DOPA. The results demonstrated clear signs of dye penetration into the parenchyma of certain brain regions (area preoptica, some hypothalamic nuclei, area ventralis tegmenti and ventral part of the pons and medulla oblongata) in addition to the areas known to be 'outside the BBB' (the circumventricular organ). There was an an apparent increase in dye penetration in these regions after IMO, most pronounced in the reticular formation of the brain stem. In the mesencephalic reticular formation ruptures of a substantial number of vessels occurred after IMO leading to massive leakage of dye into surrounding brain parenchyma. The main finding after L-DOPA administration was indications of a more efficient decarboxylation and trapping of L-DOPA in most brain regions after IMO. The findings of dye penetration in certain brain regions, which are known to be involved in autonomic regulation, may reflect possible ways of chemical communication between the circulation and neuronal structures in these regions and/or possibly constitute the basis for inactivation processes for transport of substances outwards from the brain as well as potential loci for adverse effects and development of pathological conditions.

Is muscle structure influenced by genetical or functional factors? A study of three forearm muscles.

Abstract: Relative fibre type composition and weights of 3 forearm muscles; the m. extensor carpi radialis longus (ECRL), m. extensor carpi radialis brevis (ECRB) and the m. brachioradialis (BR) from both the left and right arm were determined. Fibre type 1 muscle weight of the ECRB, which co-contracts posturally during gripping, was significantly greater in the right than the left forearm. Weights of type 2 fibres in this muscle were, however, similar in the left and right arm. Fibre type weights of both ECRL and BR were also similar in both arms. For all these muscles, intra-individual co-variation in relative fibre type occurrence was found. It is proposed that genetic factors may play a role in determining the relative fibre type composition at least as far as the upper extremities are concerned. However, functional demands are also important determining factors for development of muscle structure.

Regional tissue fluid pressure in rat calf muscle during sustained contraction or stretch.

Abstract: The tissue fluid equilibration pressure in central and peripheral regions of rat calf muscles has been measured by needles with large smoothed sideholes. Short equilibration periods were normally achieved although saline was not infused. Tissue fluid pressure during rest remained constant at -2 to 0 mmHg. During sustained isometric contraction the average tissue fluid pressure rose almost linearly with increasing force of contraction. The average pressure in the central inner zone of the muscle reached 220 +/- 80 mmHg during maximal force, whereas the average pressure in the outer peripheral zone increased to 85 +/- 56 mmHg, markedly less than in the central zone. Thus, this difference in regional tissue pressure may possibly explain the greater impediment to blood flow in central than in peripheral regions during contraction shown previously by Wisnes & Kirkebo (1976). Although a corresponding regional pressure difference was observed during passive stretch of the muscle, the absolute tissue pressures were much smaller. However, the heterogeneous pattern of muscle fiber directions and relative displacement of various muscle elements during work, may induce shear forces causing focal vessel obstructions that are different during contraction and stretch.

Neural beta-adrenergic dilatation of the facial vein in man. Possible mechanism in emotional blushing

Abstract: Ring preparations of the superficial buccal segment of the human facial vein, taken from extirpated tissue in 12 patients during neck surgery, were studied in vitro. The vein developed a maintained intrinsic myogenic tone in response to passive stretch and was supplied with alpha- as well as beta-adrenoceptors, both of which could be influenced by transmural nerve stimulation (TNS) and noradrenaline. These unusual characteristics for a vein are basically similar to the ones described for the rabbit facial vein by Pegram, Bevan & Bevan (1976). In man there seemed to be an inter-individual difference with regard to the abundance of 'innervated' alpha- and beta-adrenoceptors. Facial vein specimens from some subjects thus responded with prompt and pronounced net dilatation to TNS with maximum at 4 Hz and those from others with net constriction with maximum at 16 Hz. The latter showed a reversal into neural beta-adrenergic dilatation after alpha-adrenergic blockade. The human external jugular vein was devoid of intrinsic tone and beta-adrenoceptors. It is tentatively proposed that a beta-adrenergic neuro-effector mechanism in superficial ramifications of the facial vein in man might be involved in the emotional blushing reaction.

Pharmacological characterization of four related substance P antagonists.

Abstract: The purpose of this pharmacological study was to further characterize 4 related substance P (SP) analogues, namely (D-Pro2, D-Phe7, D-Trp9)-SP (I), (D-Pro2, D-Trp7.9)-SP (II), (D-Arg1, D-Pro2, D-Phe7, D-Trp9)-SP (III) and (D-Arg1, D-Pro2, D-Trp7.9)-SP (IV). At a concentration of 10-4 M they were found to have little or no smooth muscle-contracting effect on the guinea-pig ileum, analogues I and II having substantially less agonist activity than III and IV. Pretreatment with the analogues inhibited the contractile responses to SP, but not to histamine or acetylcholine. Of the 4 analogues, II was found to be the most potent SP antagonist. The contractile responses to physalaemin and eledoisin were also inhibited by analogue II. The concentration-response curves for SP were shifted in parallel to higher concentrations in the presence of the analogues. The pA2-values derived from Schild plots were 4.61 for (I), 5.43 for (II), 4.69 for (III) and 5.11 for (IV). Except for (I) the slopes of the regression lines of the Schild plots were close to unity. The data are consistent with simple competitive antagonism over the concentration ranges investigated. Without being secretagogues per se, the analogues inhibited SP-stimulated salivary secretion in the rat. Physalaemin-stimulated secretion was inhibited by analogue II. The inhibitory effect of sequences with D-Arg1 instead of L-Arg1 seemed to be of longer duration. Not one of these analogues blocked the blood pressure-lowering effect of SP, which indicates the existence of more than one type of SP receptor. This study has shown that 4 related SP analogues specifically inhibit the actions of SP and structurally related peptides physalaemin and eledoisin, both in vitro and in vivo. Analogues II-IV seem to inhibit in a simple competitive manner. (D-Pro2, D-Trp7.9)-SP was the most potent of the 4 SP antagonists.

Quantitative measurements of the alcohol concentration and the temperature of breath during a prolonged exhalation

Abstract: After healthy men drank a moderate dose of alcohol their breath-alcohol concentrations and breath-temperatures were quantitatively determined as a function of expired-volume. All test were made in the post-adsorptive phase of ethanol metabolism and breath samples were analysed by gas-liquid chromatography. The temperatures of breath rose steadily from start to end of exhalation with a mean of 34.48 degrees C after a forced vital capacity (FVC) maneuver. The standard deviation of a single measurement of breath-temperature in randomly selected subjects was +/- 0.402 degrees C. No statistically significant increases in the temperature of breath were noted after an expired volume of 70% FVC. At average expired-breath volumes of 13.5%, 26.2%, 52.2%, 71.7% and 94.2% FVC the breath-temperatures were 33.3 degrees C, 33.5 degrees C, 33.9 degrees C, 34.1 degrees C and 34.4 degrees C whereas breath-alcohol concentration were 79.7%, 85.9%, 90.5%, 95.9% and 98.8% of the 100% FVC alcohol levels. When I corrected for the lower temperatures of breath in the early stages of expiration, the concentrations of alcohol were 86.6%, 90.8%, 93.5%, 96.5% and 98.5% of the 100% FVC levels. These results show that at least 70% of a man's vital capacity must be discarded before a breath-concentration plateau for ethanol develops. But even after a discard breath-volume of 10% FVC the concentration of alcohol reaches 80% of the level in end-expiratory breath. I suspect that ethanol dissolves in the mucous-membranes of the upper respiratory tract and equilibrates with breath in the airway dead-space and in the mouth.

Supersensitivity to substance P and physalaemin in rat salivary glands after denervation or decentralization.

Abstract: Substance P, a putative neurotransmitter in mammals, and physalaemin, present in the skin of an amphibian, are both undecapeptides and belong to the family of tachykinins. The secretory effect of these tachykinins on parotid and submaxillary glands of the rat was examined. Dose-response curves showed that in the unoperated glands maximal secretory responses were obtained to an intravenous dose of 5-10 micrograms/kg of the tachykinins, that the amount of saliva secreted from the submaxillary gland was twice that from the parotid gland, and that physalaemin was more potent than substance P. Parasympathetic denervation of the parotid gland and decentralization of the submaxillary gland caused a marked sensitization to the tachykinins, as judged by lowered threshold doses for secretion and increased secretory responses to a series of submaximal doses 3 weeks postoperatively. Sensitization was less marked after sympathetic denervation and decentralization; in the parotid gland decentralization caused, in fact, no sensitization while in the submaxillary gland the degree of sensitization was about the same after the two types of operation. The tachykinins acted directly on the gland cells and the effect was not exerted via cholinergic, alpha-adrenergic or beta-adrenergic receptors. The pattern of sensitization to the tachykinins, found in the present study, after the different types of operation is similar to that previously found to cholinergic and alpha-adrenergic agonists and different from that to a beta-adrenergic agonist. Studies by others have shown that in the rat parotid gland peptidergic receptors share a common intracellular pathway with cholinergic and alpha-adrenergic receptors, whereas beta-adrenergic receptors use another pathway. In the present study it is suggested that this intracellular arrangement is of importance for the development of supersensitivity.

On the significance of the respiratory exchange ratio after different diets during exercise in man

Abstract: Total respiratory exchange ratio (R) was compared to the respiratory exchange ratio over the legs (RQL) during exercise after different diets, to evaluate if R (which represents a mean for the whole body) can be used to estimate the relative proportions of fat and carbohydrate oxidation in exercising muscle. One important prerequisite for this is a steady state acid base balance, 7 subjects were studied at rest and during the later part of a 25 min exercise (65% of Vo2 max) on two occasions, the first preceded by a fat rich diet and the second by a carbohydrate rich diet. Oxygen uptake, R and arterial-femoral venous differences for [O2], [CO2], PCO2 and pH and arterial concentrations for lactate and beta-hydroxybutyrate were measured. Respiratory exchange ratio over the exercising legs (RQL) and ventilation/oxygen uptake were calculated. Arterial pH, PCO2, lactate and beta-hydroxybutyrate as well as specific ventilation attained steady levels during the later part of exercise after both diets. Although arterial lactate and beta-hydroxybutyrate differed between the diets, the arterial pH and specific ventilation were the same. Both R and RQL were higher after the carbohydrate than after the fat diet and there was no systematic difference between R and RQL. Therefore, it seems likely that R estimates the proportion of fat and carbohydrate oxidation in skeletal muscle during submaximal exercise after extreme diets.