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Biomedical subjects

S Lundin

Publications and source records attributed to S Lundin.

At least 19 recordsLinked to original sources
PubMed1992

Degradation and inactivation of rat atrial natriuretic peptide 1-28 by neutral endopeptidase-24.11 in rat pulmonary membranes.

Atrial natriuretic peptide (ANP), a 28-residue peptide with cardiovascular and renal effects, is rapidly cleared from the circulation. Beside renal clearance, an extra-renal metabolism by the enzyme neutral endopeptidase-24.11 (NEP-24.11) has been proposed, since specific NEP-24.11-inhibitors increase endogenous plasma-ANP. NEP-24.11 is present in rat lung but its significance for ANP hydrolysis within the lung is unclear. The aim of this study was to investigate a possible degradation of rat ANP in a membrane preparation from rat lung. Hydrolysis products of ANP were separated by HPLC and further characterized by a pulmonary artery bioassay, by radioimmunoassay with different antisera, by peptide sequencing and by masspectrometry. Rat pulmonary membranes degraded ANP to one main metabolite lacking biological activity and with poor cross-reactivity to an antiserum recognising the central ring-structure of the peptide. Formation of the hydrolysis product was prevented by the NEP-24.11-inhibitor phosphoramidon (1 microM). Peptide sequencing of the metabolite revealed a cleavage between Cys7 and Phe8, which was confirmed by mass-spectrometry. The metabolite had an HPLC elution time identical to that of the product formed by purified porcine NEP-24.11. These findings suggest that ANP is metabolized and inactivated by endopeptidase-24.11 in rat lungs, the first organ exposed to ANP released from the heart.

Amino Acid Sequence↗
PubMed1992

Contractile effect and tissue content of arginine vasopressin in the urinary bladder of Brattleboro rats with hereditary diabetes insipidus.

1. Urinary bladders from male rats of the Brattleboro strain with hereditary diabetes insipidus (DI) were analyzed for presence of immunoreactive arginine vasopressin (ir-AVP). Healthy rats were used as controls. 2. Bladders from the DI rats were heavier than controls. Concentration of ir-AVP was lower in DI bladders, but total amount of ir-AVP was similar to that in controls. 3. EC50 values for the AVP concentration-response relations were similar for control and DI bladder strips. Maximum response to AVP relative to response to K+ high solution was lower in the DI group. 4. An AVP receptor antagonist that significantly blocked response to exogenous AVP had no effect on response to field stimulation. 5. We suggest that AVP is synthetized locally and that AVP is not the non-adrenergic non-cholinergic transmitter responsible for the atropine resistant contraction in rat bladder.

Animals↗
PubMed1991

Administration of antidiuretic peptide (DDAVP) by way of suction de-epithelialised skin.

Transdermal drug delivery seems a promising way of achieving complete, predictable absorption, but the epidermis is a barrier for most drugs. A new technique for transdermal drug delivery, in which a small patch of epidermis was removed, was tested in seven healthy volunteers by means of the antidiuretic peptide 1-deamino-8-D-arginine vasopressin (DDAVP). The epithelium of a small area of forearm skin (diameter 5 mm) was removed painlessly, and in a standard way, by a simple device operating at a present vacuum. DDAVP was given by way of improvised occlusive reservoirs. Plasma DDAVP concentration/time curves conformed closely with zero-order kinetics, which suggests that the bioavailability approached 100%, corresponding to that for direct intravenous infusion. Four volunteers were given DDAVP daily for 4 days by way of the de-epithelialised site; there were no signs that re-epithelialisation hindered permeation. All plasma DDAVP values substantially exceeded the lowest effective therapeutic concentration for patients with diabetes insipidus. The vacuum removal of the epithelium caused pronounced hyperaemia in the de-epithelialised dermis (assessed by laser doppler flow measurement); the hyperaemia persisted, unaffected by DDAVP, and may have contributed to the efficient permeation. The skin spot appeared normal at 6 weeks.

Administration, Cutaneous↗
PubMed1991

Differences in transport rate of oxytocin and vasopressin analogues across proximal and distal isolated segments of the small intestine of the rat.

The transmural intestinal passage of some oxytocin and vasopressin analogues (oxytocin, OT; [Mpa1, D-Arg8]vasopressin, dDAVP; [Mpa1, Tyr (OMe)2, carba6]oxytocin, carbetocin; [Mpa1, D-Tyr (OEt)2, Thr4, Orn8]vasotocin, antocin II; [Mpa1, D-Tyr (OEt)2, Thr4, desPro7Orn8Gly9NH2]tocinoic acid-NH(CH2)3NH2, desPOG-antocin II-NH(CH2)3NH2) was studied using isolated proximal and distal segments in the rat. All peptides (measured as peptide-like immunoreactivity) displayed a higher transport rate across distal intestinal segments as determined by radioimmunoassay (RIA). The smallest peptide, des POG-antocin II-NH(CH2)3NH2, was transported at the fastest rate. No correlation of lipophilicity with transport rate was observed. Determination of the amount of peptide remaining in the mucosal media at the end of the incubation period by HPLC did not reveal any visible degradation products. However, the large difference in transport rate between [3H]OT and immunoreactive OT indicates mucosal metabolism of this peptide. [3H]d-DAVP was distributed in a larger mucosal volume than the extracellular space marker [3H]inulin, indicating tissue uptake, but was too low (less than 100% of buffer concentration) to make an active transport mechanism likely. The differences in peptide transport rates between proximal and distal intestinal segments are most likely due to a higher distal paracellular permeability despite a decreased absorptive surface area at this region.

Amino Acid Sequence↗
PubMed1991

Biliary excretion of the vasopressin analogue DDAVP after intraduodenal, intrajugular and intraportal administration in the conscious pig.

The biliary excretion of the vasopressin analogue 1-deamino-8-D-arginine vasopressin (dDAVP) was determined in the pig after three administration routes, intrajugular venous, intraportal venous and intraduodenal. In all cases the biliary excretion was less than 1% of the administered dose. The plasma/bile concentration ratio was less than 1:1. A significant first-pass effect was found when the liver was exposed to a high intraportal dose of dDAVP. Possible uptake and degradation/biotransformation was evaluated by incubating [3H]dDAVP with liver tissue slices showing that [3H]dDAVP was rapidly removed from the incubation medium. The following conclusions can be drawn from these experiments: 1) The intestinal mucosa constitutes the major barrier to intestinal absorption of dDAVP. 2) dDAVP is excreted in bile in small amounts. 3) Indirect evidence suggests that the dDAVP molecule is degraded/biotransformed in the liver at its C-terminus.

Animals↗
PubMed1991

Studies on binding sites, contents, and effects of AVP in isolated bladder and urethra from rabbits and humans.

The binding sites, contents, and effects of arginine vasopressin (AVP) were studied in isolated bladder and urethral preparations from rabbits and humans. In all tissues, higher levels of AVP-like immunoreactivity (AVP-LI) were detected than those normally found in plasma. Radioligand membrane binding studies using [3H]AVP as the ligand revealed the existence of a single population of binding sites in the rabbit bladder, and displacement experiments indicated that the receptor was of the V1 subtype. By autoradiography, [3H]AVP binding sites in the rabbit bladder were shown to be located on both circularly and longitudinally oriented smooth muscle cells, as well as in the submucosa at the part adjacent to the urothelium. In the rabbit urethra, the binding sites were confined mainly to the circular smooth muscle layer. Neither radioligand membrane binding studies nor autoradiography revealed any specific [3H]AVP binding sites in the human bladder. AVP contracted rabbit bladder and urethral preparations concentration dependently. The contractions were inhibited by the V1-receptor selective antagonist A16 in a noncompetitive manner. However, A16 had no effects on contractions elicited by electrical-field stimulation. In preparations of the human bladder and urethra, AVP in concentrations up to 10(-5) M did not have any contractile effects. These results suggest that in the rabbit and human lower urinary tract, AVP-LI is synthesized locally and/or extracted from the circulation. It is unlikely that AVP is directly involved in the neurotransmission in these tissues, although in the rabbit bladder and urethra a modulatory role cannot be excluded.

Adult↗
PubMed1991

Can galvanic skin response be used as a quantitative estimate of sympathetic nerve activity in regional anesthesia?

To study the relationship between skin sympathetic nerve activity and changes in skin resistance (galvanic skin response--GSR), efferent sympathetic and sensory nerves to the hand were blocked by an axillary nerve blockade in 15 healthy subjects. Subsequently, intraneural electrical stimuli in the median nerve distal to the axillary nerve block were used to evoke changes in skin resistance and in water vapor partial pressure in the sensory and sympathetically denervated hand. With increasing frequency of stimulation, skin resistance decreased and water vapor partial pressure increased until stimuli exceeded 10 Hz. When an additional burst of impulses was added to the background stimulation, GSR amplitude varied in a nonlinear fashion with the background frequency. Stimulation-induced GSR was completely abolished in a dose-dependent manner by systemically (intravenously) administered atropine. The results indicate that GSR depends on the preceding level of nerve traffic in the sympathetic sudomotor nerve fibers. Consequently, skin resistance recordings cannot be used to quantify sympathetic nerve traffic and thus do not express the completeness of sympathetic blockade in regional anesthesia.

Adult↗
PubMed1990

Content and contractile effect of arginine vasopressin in rat urinary bladder.

The contractile response of normal male rat urinary bladders to exogenous arginine vasopressin (AVP) and the AVP content of normal and denervated bladders were investigated. In isolated detrusor strips, the maximal response to AVP was about 12% of the contraction elicited by KCl (124 mM), and the EC50 value was 1.03 +/- 0.13 x 10(-8) M. The response to transmural nerve stimulation was not affected by the presence of AVP. Addition of an AVP receptor antagonist strongly reduced the response to exogenous AVP, but did not affect contractions in response to nerve stimulation. In normal bladders, the concentration of immunoreactive (ir) AVP was 29 +/- 6.0 x 10(-15) mol/g. Three days after denervation the bladders had increased 2.4-fold in weight. At this time, the concentration of irAVP was not different from the control value, but the total content had increased significantly. Characterization of bladder irAVP by reverse-phase HPLC revealed that 66.5% of the total immunoreactivity eluted in the position of synthetic AVP. The results suggest a non-neuronal localization of bladder irAVP.

Animals↗
PubMed1990

Effects of epidural anesthesia on sympathetic nerve discharge to the skin.

Direct intraneural recordings of skin sympathetic activity (SSA) were performed to determine the magnitude of blockade of sympathetic fibers to the lower extremities during epidural anesthesia. Lumbar epidural catheters were inserted in nine volunteers. Multiunit postganglionic sympathetic activity was recorded in a skin fascicle of the peroneal nerve before and after injection of 4 ml of mepivacaine 2% epidurally, followed by an additional 12-16 ml after 5 min. Arousal stimuli such as sudden loud noises and noxious electrical skin stimulation were used to elicit transient sympathetic activation. Epidural anesthesia with upper level of sensory blockade at T4-T8 (n = 7) completely blocked spontaneous SSA and no detectable skin sympathetic activity could be provoked by arousal stimuli later than 14 min after the test dose. Sympathetic blockade was accompanied by marked increases in foot skin blood flow and loss of skin resistance responses to arousal. Epidural anesthesia with sensory blockade up to T10-11 (n = 2) only produced a partial sympathetic blockade. The result shows that epidural anesthesia with sensory blockade at T8 or above is equally as effective as injections of local anesthetics directly at postganglionic nerve fibers or ganglionic blockade in producing a complete sympathetic blockade of intraneurally recorded SSA. This neural blockade was paralleled by skin vasodilatation and a loss of sudomotor responses in the foot.

Adult↗
PubMed1990

Regional differences in vascular responses in the human uterus.

Tissue specimens from the fundus, isthmus and distal cervix were obtained from 14 women at hysterectomy at various phases of the menstrual cycle. Ring preparations of small intramyometrial and intracervical arteries were dissected and mounted in organ baths; isometric tension was recorded and responses to contractile agents were studied. The amplitude of responses to K+ (124 mmol/l) of the vessel preparations ranked fundus greater than or equal to isthmus greater than cervix. While similar pD2 values for noradrenaline (NA) were found, the Emax values ranked cervix greater than or equal to isthmus greater than or equal to fundus (cervix greater than fundus). The pD2 values for arginine-vasopressin (AVP) showed minor differences, while the Emax values for this peptide ranked fundus greater than or equal to isthmus greater than or equal to cervix (fundus greater than cervix). Arteries from the fundus and isthmus displayed weak, inconsistent contractile responses to prostaglandin F2 alpha, but more pronounced contractions were induced by this prostanoid in arterial preparations from the distal cervix. The results suggest regional differences in vascular mechanical responses to endogenous vasoactive agents in the human uterus.

Adult↗
PubMed1989

Decrease in plasma volume from intraabdominal trauma in rats.

Intraabdominal surgery tends to lower circulating blood volume by mechanisms unrelated to bleeding. This phenomenon was investigated in chloralose anesthetized rats. Plasma volume was determined with radiolabelled albumin. Animals were subjected to a standardized abdominal trauma, eliciting minimal bleeding and evaporation, and others served as controls. The trauma decreased plasma volume and increased hematocrit significantly, whereas the plasma concentration of labelled albumin followed a similar time course in traumatized animals and in controls. It is concluded that experimental abdominal trauma may decrease blood volume by a loss of fluid with virtually the same albumin concentration as that of plasma.

Abdomen↗
PubMed1989

Degradation of [mercaptopropionic acid1, D-arginine8]-vasopressin (dDAVP) in pancreatic juice and intestinal mucosa homogenate.

The degradation of the vasopressin analogue dDAVP was studied by reversed phase high-performance liquid chromatography (HPLC) after incubations in pancreatic juice and intestinal mucosa homogenates. dDAVP remained stable in pancreatic juice for a period of 60 min. while the parent hormone arginine vasopressin (AVP) was completely degraded within 5 min. In intestinal mucosa homogenates dDAVP was degraded with half-lives of 9 min. (fast phase) and 161 min. (slow phase), about four times slower than AVP. By amino-acid analysis it was confirmed that the metabolite [Mpa1, Des-D-Arg8-Gly9 NH2]-vasopressin was gradually produced. No other breakdown products were observed. These findings may be of value for the further development of more stable peptide analogues which may be effective upon oral administration.

Animals↗
PubMed1989

Immunoreactive oxytocin and vasopressin in the non-pregnant human uterus and oviductal isthmus.

The regional distribution of immunoreactive OT and AVP in the human uterus was investigated. Specimens of non-pregnant human uterus and oviduct were homogenized and extracted. The tissue levels exceeded the plasma concentrations of the peptides. The largest quantities of both peptides were found in the cervix and oviductal isthmus. The amounts found in the uterine fundus and isthmus were, however, not significantly different. Only 23% of immunoreactive OT eluted in the position of standard peptide on high-performance liquid chromatography. All immunoreactive AVP eluted with standard AVP after additional ether extraction of octadecasilyl extracts. We conclude that the human uterus contains materials immunologically and chromatographically identical to oxytocin and vasopressin.

Adult↗
PubMed1989

Intraneural recording of muscle sympathetic activity during epidural anesthesia in humans.

The extent and magnitude of sympathetic blockade during epidural anesthesia have previously been assessed only by indirect methods. In this study, direct intraneural recordings of muscle sympathetic activity (MSA) in the peroneal nerve was performed to determine the profundity of blockade of sympathetic fibers to the lower extremities during epidural anesthesia. Lumbar epidural catheters were inserted in nine volunteers. Multiunit postganglionic sympathetic activity was recorded in a muscle fascicle of the peroneal nerve before and after epidural injection of 4 mL of 2% mepivacaine followed by an additional 12-16 mL after 5 min. Apnea (30-60 s) was used to elicit transient sympathetic activation. The upper level of sensory blockade was T-3 to T-10. Muscle sympathetic activity decreased after epidural blockade with no spontaneous or apnea-induced sympathetic bursts observed later than 11 min after injection of the initial test dose. Sympathetic blockade was accompanied by increase in foot skin blood flow as well as loss of skin resistance responses to arousal. Results show that epidural anesthesia with sensory blockade above T-10 to T-11 blocks spontaneous peroneal MSA as well as the marked sympathetic activation induced by apnea.

Anesthesia, Epidural↗
PubMed1988

Immunoreactive arginine vasopressin (AVP) and effects of AVP in the human vas deferens.

Immunoreactive (IR) arginine vasopressin (AVP) was found to occur in the epididymal part of the human vas deferens. Segments from nine different subjects all contained IR-AVP in concentrations ranging from 37 to 717 fmol/gm. wet weight, concentrations severalfold higher than those normally found in the circulation. IR-AVP was shown by high performance liquid chromatography to elute in the same position as synthetic AVP. AVP added to isolated preparations of the human vas deferens induced concentration-related repetitive phasic contractions without significant changes of baseline tension. These contractions seemed to be mediated via stimulation of vasopressin V1-receptors and were abolished in the presence of vasopressin antagonists. Contractions induced by electrical field stimulation were frequency-dependent and sensitive to tetrodotoxin and prazosin. They were not affected by the vasopressin antagonists used. AVP increased the response to electrical field stimulation and this effect was inhibited by vasopressin antagonists. The results suggest either that circulating AVP is taken up and accumulated by the human vas deferens, and/or that AVP is synthesized locally. They do not suggest co-release of AVP and noradrenaline from nerve endings. The physiological role of the AVP occurring in the human vas deferens remains to be established.

Adult↗
PubMed1988

Decreased passage of the nonapeptide dDAVP over the intestinal epithelium during development in the young rat.

The nonapeptide 1-deamino-cysteine-8-D-arginine vasopressin (dDAVP) was gavage-fed together with cow's milk whey protein to young, developing rats. The transepithelial passage of dDAVP in the gastrointestinal (GI) tract was assessed by a specific RIA as immunoreactive levels in blood serum extracts and as urinary excretion of dDAVP 0.5-8 h after feeding. In 14-day-old rats the passage of dDAVP was higher than in 30-day-old rats, since the 14-day-old rats had significantly higher serum levels (5-10 times) 0.5-2 h after feeding and a urinary excretion approaching 0.15% of the administered amount after 8 h. In the 30-day-old rats urinary excretion increased up to 0.05% after 2 h and then levelled off. It was also clear that 30-day-old rats had a slower transfer to and faster elimination from serum than 14-day-old rats. dDAVP appeared to be passed over the GI tract mucosa independently of intestinal proteolysis since feeding it to 30-day-old rats together with the proteinase inhibitors, soya-bean trypsin inhibitor and pepstatin did not influence the serum or urinary levels. Thus, dDAVP was taken up from the GI tract into the blood circulation and excreted in the urine of young rats. The decrease in the passage of dDAVP found around weaning appears to be related to developmental processes affecting the permeability of the intestinal epithelium rather than intestinal proteolysis.

Animals↗
PubMed1988

Changes in renal sympathetic nerve activity during experimental septic and endotoxin shock in conscious rats.

Changes in postganglionic renal sympathetic nerve activity, arterial pressure, and heart rate were measured in conscious rats during intravenous infusion of live E. coli bacteria (10(9)/h) or bolus injection of E. coli endotoxin (20 mg/kg). Bacteria infusion was associated with a marked and parallel increase in heart rate and sympathetic activity with only minor changes in mean arterial pressure. The early response to bolus injection of endotoxin was a short-lasting decrease in mean arterial pressure combined with a marked increase in sympathetic activity and heart rate, probably due to baroreceptor unloading. However, when mean arterial pressure returned to pre-endotoxin levels, sympathetic activity and heart rate remained markedly elevated, indicating a partly nonreflexogenic increase in central sympathetic outflow. This study using direct nerve recordings of sympathetic activity in conscious animals confirms earlier clinical observations of an increased activity of the sympathetic nervous system in septic shock.

Animals↗