Signalling pathways involved in sildenafil-induced relaxation of human bladder dome smooth muscle.

BACKGROUND AND PURPOSE: The mechanism(s) of action responsible for the beneficial effects of phosphodiesterase 5 (PDE5) inhibitors including sildenafil on lower urinary tract symptoms suggestive of benign prostate hyperplasia are unclear. In particular, the role of the NO-cGMP signalling pathway in regulating human bladder dome smooth muscle relaxation is questionable. Thus, we assessed the ability of a PDE5 inhibitor, sildenafil, to relax such tissue, and identified the signalling pathways involved in this relaxation. EXPERIMENTAL APPROACH: Human bladder samples were obtained from 20 patients with no overactive bladder undergoing cystectomy for bladder cancer. Detrusor strips were mounted isometrically in Krebs-HEPES solution. Concentration-response curves for sildenafil (10 nM-30 microM) were generated in the presence of various inhibitors on carbachol-induced pre-contraction. KEY RESULTS: Sildenafil relaxed carbachol-pre-contracted human detrusor strips, starting at 3 microM. This effect was not modified by NO donors, S-nitroso-N-acetylpenicillamine (10 microM) or sodium nitroprusside (300 nM), but was significantly inhibited by inhibition of guanylate cyclase (with ODQ, 10 microM) or adenylyl cyclase (with MDL-12,330A, 10 microM), by the ATP-sensitive potassium channel inhibitor, glibenclamide (10 microM), or inhibition of the large (with iberiotoxin, 30 nM) or small (with apamin, 100 nM) conductance calcium-activated potassium channels. CONCLUSIONS AND IMPLICATIONS: Sildenafil-induced relaxation of human detrusor smooth muscle involved cGMP-, cAMP- and K(+) channel-dependent signalling pathways, with a minor contribution from NO. The effect of this sildenafil-induced relaxation on the clinical benefit of PDE5 inhibitors on urinary storage symptoms in men deserves further investigation.

Endothelial dysfunction in insulin-resistant rats is associated with oxidative stress and COX pathway dysregulation.

Because insulin resistance is inevitably associated with cardiovascular complications, there is a need to further investigate the potential involvement of oxidative stress and the cyclo-oxygenase (COX) pathway in the vascular modifications associated to this pathological context. Endothelial function was evaluated in control and fructose-fed rats (FFR) by i) in vitro study of endothelium-dependent and -independent relaxations of aortic rings, and ii) in vivo telemetric evaluation of pressor response to norepinephrine. After 9 weeks of diet, FFR displayed hypertriglyceridemia, hyperinsulinemia and exaggerated response to glucose overload. Aortic rings from control rats and FFR exhibited comparable endothelium-dependent relaxations to Ach. In the presence of indomethacin, relaxations were significantly reduced. FFR showed exaggerated pressor responses to norepinephrine that were abolished with indomethacin. Urinary nitrites/nitrates, 8-isoprostanes and thromboxane B2 excretion levels were markedly enhanced in FFR, whereas the plasma levels of 6-keto prostaglandin F1alpha were unchanged. In conclusion, fructose overload in rats induced hypertriglyceridemia and insulin resistance associated with an enhanced oxidative stress. This was associated with COX pathway dysregulation which could be one of the contributors to subsequent vascular dysfunction. Consequently, reduction of oxidative stress and regulation of the COX pathway could represent new potential therapeutic strategies to limit vascular dysfunction and subsequent cardiovascular complications associated with insulin resistance.

Piboserod (SB 207266), a selective 5-HT4 receptor antagonist, reduces serotonin potentiation of neurally-mediated contractile responses of human detrusor muscle.

The aim of this study is to evaluate the potency of piboserod (SB 207266), a selective 5-HT(4) receptor antagonist, at inhibiting the 5-HT(4)-mediated potentiating effect of serotonin (5-HT) on the neurally-mediated contractile responses of human detrusor strips to electrical field stimulations (EFS). Strips of human detrusor muscle were mounted in Krebs-HEPES buffer under a resting tension of 500 mg and EFS (20 Hz, 1 ms duration at 300 mA for 5 s) was applied continuously at 1 min intervals. After stabilization of the EFS-induced contractions, concentration-response curves to 5-HT (0.1 nM-100 microM) were constructed in the absence or presence of 1 or 100 nM of piboserod. The experiments were performed in the presence of methysergide (1 microM) and ondansetron (3 microM) to block 5HT(1)/5HT(2) and 5-HT(3) receptors, respectively. 5-HT potentiated the contractile responses to EFS of human bladder strips in a concentration-dependent manner, with a maximum mean of 60.0+/-19.9% of the basal EFS-evoked contractions. Piboserod did not modify the basal contractions but concentration-dependently antagonized the ability of 5-HT to enhance bladder strip contractions to EFS. In presence of 1 and 100 nM of piboserod, the maximal 5-HT-induced potentiations were reduced to 45.0+/-7.9 and 38.7+/-8.7%, respectively. A mean apparent antagonist dissociation constant value (K(B)) of 0.56+/-0.09 nM was determined. These data show the ability of piboserod to antagonize with high potency the enhancing properties of 5-HT on neurally-mediated contractions of isolated human bladder strips. Therefore, the 5-HT(4) receptor might represent an attractive pharmacological target for the treatment of overactive bladder.

Nitric oxide decreases renal medullary Na+, K+-ATPase activity through cyclic GMP-protein kinase G dependent mechanism.

The aim of this study was to investigate the effect of nitric oxide on renal Na+,K(+)-ATPase and ouabain-sensitive H+,K(+)-ATPase activities. The study was performed in male Wistar rats. The investigated substances were infused under general anaesthesia into abdominal aorta proximally to the renal arteries. The activity of ATPases was assayed in isolated microsomal fraction. NO donor, S-nitroso-N-acetylpenicillamine (SNAP), infused at doses of 10(-7) and 10(-6)mol/kg/min decreased medullary Na+,K(+)-ATPase activity by 29.4% and 45.2%, respectively. Another NO donor, spermine NONOate, administered at the same doses reduced Na+,K(+)-ATPase activity in the renal medulla by 31.7% and 46.5%, respectively. Neither of NO releasers had any effect on Na+,K(+)-ATPase in the renal cortex and on either cortical or medullary ouabain-sensitive H+,K(+)-ATPase. Infusion of NO precursor, L-arginine (100 micromol/kg/min), decreased medullary Na+,K(+)-ATPase activity by 32.2%, whereas inhibitor of nitric oxide synthase, L-NAME (10 nmol/kg/min), increased this activity by 20.7%. The effect of synthetic NO donors was mimicked by 8-bromo-cGMP and blocked by inhibitors of soluble guanylate cyclase, ODQ or methylene blue, as well as by specific inhibitor of protein kinase G, KT5823. In addition, inhibitory effect of either SNAP or 8-bromo-cGMP on medullary Na+,K(+)-ATPase was abolished by 17-octadecynoic acid (17-ODYA), which inhibits cytochrome P450-dependent metabolism of arachidonic acid. These data suggest that NO decreases Na+,K(+)-ATPase activity in the renal medulla through the mechanism involving cGMP, protein kinase G, and cytochrome P450-dependent arachidonate metabolites. In contrast, NO has no effect on Na+,K(+)-ATPase in the renal cortex and on either cortical or medullary ouabain-sensitive H+,K(+)-ATPase.

The opposite effects of cyclic AMP-protein kinase a signal transduction pathway on renal cortical and medullary Na+,K+-ATPase activity.

Cyclic AMP-protein kinase A (PKA) pathway plays an important role in signal transduction in renal tubular cells, however, its role in transport regulation is not completely established. The aim of this study was to investigate in vivo the effect of PKA on renal Na, K-ATPase activity. The study was performed in male Wistar rats. The animals were anaesthetized with pentobarbital and investigated drugs were infused through the catheter inserted into the abdominal aorta. Na+,K+-ATPase activity was assayed in an isolated microsomal fraction of the renal cortex and medulla. Cell-permeable cAMP analogue, dibutyryl-cAMP (db-cAMP), dose-dependently stimulated Na+,K+-ATPase in the renal cortex and inhibited in the renal medulla. Maximal stimulation (+38.5%) and inhibition (-46.8%) were observed at a dose of 10(-6) mol/kg/min. Measurement of Na+,K+-ATPase activity at different Na' concentrations revealed that in the renal cortex db-cAMP increased Vmax of the enzyme without any effect on sodium affinity, whereas in the renal medulla decrease in Vmax was accompanied by decreased sodium affinity, evidenced by elevated K(0.5) for sodium. The effect of db-cAMP was mimicked by the infusion of either adenylate cyclase activator, forskolin, or inhibitor of phosphodiesterase, IBMX. Both stimulatory and inhibitory effects of db-cAMP were prevented by pretreatment with protein kinase A inhibitor, KT 5720 (10(-8) mol/kg/min) but not by inhibitor of protein kinase G, KT 5823. The inhibitory effect in the renal medulla was partially blocked by pretreatment with either ethoxyresorufin or 17-ODYA - two nonspecific inhibitors of cytochrome P450-dependent arachidonate metabolism, whereas an inhibitor of epoxygenase, miconazole, was not effective. Infusion of 20-hydroxyeicosatetraenoic acid (20-HETE) at a dose of 10(-10) mol/kg/min decreased medullary Na+,K+-ATPase activity by 24.2%. Exogenous protein phosphatases inhibitor, okadaic acid (OA, 10(-8) - 10(-7) mol/kg/min) caused dose-dependent decrease in renal medullary Na+,K+-ATPase activity, maximally by 31.9%, but had no effect in the renal cortex. The effects of OA and db-cAMP in the renal medulla were not additive. When OA administration (10(-7) mol/kg/min) was followed by 20-HETE (10(-10) mol/kg/min), medullary Na+,K-ATPase activity decreased by 48.6% and was similar as after db-cAMP. We conclude, that cAMP-PKA pathway activates Na+,K+-ATPase in the renal cortex and inhibits in the renal medulla. The inhibitory effect is partially mediated by cytochrome P450-dependent arachidonate metabolites and possibly also by PKA-dependent inhibition of protein phosphatases.

Involvement of Rho-kinase and the actin filament network in angiotensin II-induced contraction and extracellular signal-regulated kinase activity in intact rat mesenteric resistance arteries.

We have previously shown that angiotensin II (Ang II) and pressure increase extracellular signal-regulated kinase (ERK) 1/2 activity synergistically in intact, pressurized resistance arteries in vitro. However, the mechanisms by which pressure and Ang II activate ERK1/2 in intact resistance arteries remain to be determined. The purpose of the present study was to investigate the involvement of Rho-kinase and the actin filament network in Ang II- and pressure-induced ERK1/2 activation, as well as in the contractile response induced by Ang II. Mesenteric resistance arteries (200 to 300 microm) were isolated, mounted in an arteriograph, and stimulated by pressure, Ang II, or both. Activation of ERK1/2 was then measured by an in-gel assay. In mesenteric resistance arteries maintained at 70 mm Hg, Ang II (0.1 micromol/L) induced contraction (29+/-1.4% of phenylephrine, 10 micromol/L-induced contraction) and significantly increased ERK1/2 activity. Selective inhibition of Rho-kinase by Y-27632 (10 micromol/L) and selective disruption of the actin filament network by cytochalasin B (10 micromol/L) both decreased the Ang II-induced contraction by 78+/-1.2% and 87+/-1.9%, respectively, and significantly diminished ERK1/2 activity. In the absence of Ang II, increasing intraluminal pressure from 0 to 70 or 120 mm Hg increased ERK1/2 activity. ERK1/2 activity at 120 mm Hg was similar to that observed at 70 mm Hg in the presence of Ang II. Pressure-induced ERK1/2 activation was markedly attenuated by cytochalasin B but not by Y-27632. These results indicate that whereas pressure-induced ERK1/2 activation requires an intact actin filament network, but not Rho-kinase, the activation of ERK1/2 and the contraction induced by Ang II require both Rho-kinase and an intact actin filament network in isolated, intact mesenteric resistance arteries.

Flow (shear stress)-induced endothelium-dependent dilation is altered in mice lacking the gene encoding for dystrophin.

BACKGROUND: Dystrophin has a key role in striated muscle mechanotransduction of physical forces. Although cytoskeletal elements play a major role in the mechanotransduction of pressure and flow in vascular cells, the role of dystrophin in vascular function has not yet been investigated. Thus, we studied endothelial and muscular responses of arteries isolated from mice lacking dystrophin (mdx mice). METHODS AND RESULTS: Carotid and mesenteric resistance arteries 120 micrometer in diameter were isolated and mounted in vitro in an arteriograph to control intraluminal pressure and flow. Blood pressure was not affected by the absence of dystrophin. Pressure-induced (myogenic), phenylephrine-induced, and KCl-induced forms of tone were unchanged. Flow (shear stress)-induced dilation in arteries isolated from mdx mice was decreased by 50% to 60%, whereas dilation to acetylcholine or sodium nitroprusside was unaffected. NG-nitro-L-arginine methyl ester-sensitive flow dilation was also decreased in arteries from mdx mice. Thus, the absence of dystrophin was associated with a defect in signal transduction of shear stress. Dystrophin was present in vascular endothelial and smooth muscle cells, as shown by immunolocalization, and localized at the level of the plasma membrane, as seen by confocal microscopy of perfused isolated arteries. CONCLUSIONS: -This is the first functional study of arteries lacking the gene for dystrophin. Vascular reactivity was normal, with the exception of flow-induced dilation. Thus, dystrophin could play a specific role in shear-stress mechanotransduction in arterial endothelial cells. Organ damage in such diseases as Duchenne dystrophy might be aggravated by such a defective arterial response to flow.

[Unilateral amblyopia without strabismus and with anisometropia]. / Jednostronne niedowidzenie bez zeza przy jednakowej wadzie refrakcji obojga oczu.

PURPOSE OF THE STUDY: To evaluate a group of patients with unilateral isometropic amblyopia according to presence of possible amblyogenic factors. MATERIAL AND METHODS: 37 patients (18 girls and 19 boys) with unilateral amblyopia without strabismus and with anisometropia of less than 1 D in any of the meridians were analysed according to such possible risk factors of amblyopia as age of examination, age of mother on delivery, sex, family history, puerperal complications, birth weight, refraction error, left or right eye. Depth of amblyopia, state of binocular vision and results of optical and pleoptical treatment were also evaluated. RESULTS AND DISCUSSION: No significant risks were found regarding the age of patient, sex, left or right eye, birth weight, age of mother on delivery, puerperal complications and family history. Refraction error was not high. Depth of amblyopia did not correlate with amount of refraction error. Central fixation was present only in 50% and stereopsis only in 42% of patients. 10 patients revealed no significant defect of fixation or binocular vision. All patients responded significantly poorly to treatment. CONCLUSIONS: Presence of amblyopia in patients with isometropia cannot be explained by genetic or puerperal risk factors. It might have developed in the period sensitive for amblyopia as a result of anisometropia that was later diminished by the process of emmetropisation or microstrabismus which was spontaneously cured. Some cases can be described as idiopathic because no defect can be detected. Early in life screening is necessary to successfully diagnose and treat amblyopia in childhood.

The effect of dietary-induced obesity on lipid peroxidation, antioxidant enzymes and total plasma antioxidant capacity.

The aim of this study was to examine the effect of dietary-induced obesity on some parameters of oxidative stress and antioxidant defence. The studies were performed in adult male Wistar rats. Control group received normal laboratory chow (62% calories as carbohydrates, 26% protein and 12% fat). High-calorie high-fat group (HCHF) was fed standard chow supplemented with lard (48% calories as carbohydrates, 20% as protein and 32% as fat) and high-calorie normal-fat group (HCNF) received standard chow and liquid diet containing sucrose, glucose, whole milk powder and soybean powder (60% carbohydrates, 26% protein, 14% fat). After 8 weeks body weight of HCHF and HCNF-fed rats was higher than body weight of controls by 9.3% and 15.2%, respectively. Plasma concentration of thiobarbituric acid-reactive substances (TBARS) increased in these groups by 43% and 52%, respectively. The activity of superoxide dismutase (SOD) decreased in HCHF group by 47.5% and in HCNF group by 21.1%. Glutathione peroxidase (GPx) activity in the blood tended to increase in both experimental groups but this was not significant. Plasma total antioxidant status (TAS) measuring the combined free radicals scavenging ability of nonenzymatic antioxidants was lower in HCHF and in HCNF group compared to control (-8.8% and -9%, respectively). The major observed lipid abnormalities were hypertriglyceridemia in HCHF group and decreased HDL-cholesterol in HCNF group. TBARS correlated negatively with SOD (r = -0.84, p < 0.001) and with TAS (r = -0.47, p < 0.05). These results indicate that obesity leads to oxidative stress which can contribute to obesity-associated diseases such as atherosclerosis, diabetes mellitus and arterial hypertension.

[Amblyopia without strabismus in context of research on concomitant strabismus]. / Niedowidzenie bez zeza w aspekcie badan nad zezem towarzyszacym.

PURPOSE: To evaluate pathogenic factors for unilateral amblyopia in the group of amblyopic patients without strabismus. MATERIAL AND METHODS: In the study 141 patients with unilateral amblyopia without strabismus were evaluated according to age, sex, visual acuity, refraction error, presence of anisometropia, age of mother on delivery, weight on birth, hereditary transmission of strabismus or refractive error, pregnancy and delivery complications, response to treatment. RESULTS: Serious birth and pregnancy complications were noted only in 14.2% of cases, hereditary transmission might be suspected in 41.2% of patients. Anisometropia was found in 72% of cases. No significant difference in prevalence of possible pathogenic or risk factors such as age, sex, birth-weight, age of mother on delivery, hereditary transmission, pregnancy or delivery complications were found between anisometropic and isometropic group. Anisometropic group had bigger refractive error and deeper amblyopia, but responded better to treatment. CONCLUSION: Etiology of amblyopia without strabismus, particularly in the group of patients with isometropia, should be associated with trauma to central nervous system either in pre-natal or early after birth period.

[Activity of malondialdehyde in rat plasma after H2 histamine receptor blockade]. / Zachowanie sie aldehydu malonowego w osoczu szczurów po blokadzie receptora histaminowego H2.

The study evaluates the effect of cimetidine (C), ranitidine (R) and famotidine (F) on the level of the plasma malondialdehyde (MDA). The tested drugs were given intraperitoneally to the male Wistar rats twice a day, during 6 weeks' period, in two doses. CI--2.85 mg/kg body weight (b.w.), R1--0.71 mg/kg b.w., F1--0.28 mg/kg b.w. The second doses (C2, R2, F2) were 10 times higher than C1, R1, F1. At the end of the 6th week of the experiment half of the animals were terminated. The remaining rats were kept for the next 6 weeks without any medications and were killed at the end of 12th week of the experiment. Blood was taken from still beating heart and centrifuged. The level of the MDA was determined from the plasma and compared to the 1 mg of the blood protein. None of administered H2 blockers changed the malondialdehyde level in serum of the experimental rats.

The mechanism of Na+, K+-ATPase inhibition by atrial natriuretic factor in rat renal medulla.

Atrial natriuretic peptide 99-126 (ANP99-126) or atrial natriuretic factor (ANF) is one of the natriuretic peptides secreted by the heart atria which produces natriuresis, diuresis and vasodilation. We examined the influence of this hormone on Na+, K(+)-ATPase activity in rat renal medulla. We found that infusion of ANF (0.087-0.26 nmol/kg/min) caused dose-dependent inhibition of medullary Na+, K(+)-ATPase activity without affecting cortical Na+, K(+)-ATPase. This inhibition was mimicked by synthetic analogue of cyclic guanosine 3',5' monophosphate, 8-bromo-cGMP. Inhibitors of phosphodiesterase (papaverine and IBMX) also reduced Na+, K(+)-ATPase activity. This enzyme was also inhibited by the activator of soluble guanylate cyclase sodium nitroprusside. The effect of ANF, sodium nitroprusside and 8-bromo-cGMP was blocked by the specific inhibitor of protein kinase G-KT5823. The inhibitor of protein phosphatases, okadaic acid mimicked the effect of ANF and if administered together with this hormone, augmented and prolonged its action. These results suggest that ANF decreases Na+, K(+)-ATPase activity in renal medulla through cGMP-protein kinase G dependent mechanism.

Biphasic effect of protein kinase C on rat renal cortical Na+, K+-ATPase.

We examined the dependence of rat renal Na+, K+-ATPase activity on protein kinase C (PKC) stimulation. Infusion of either phorbol 12, 13-dibutyrate (PDBu) or phorbol 12-myristate 13-acetate (PMA) into rat abdominal aorta resulted in dose-dependent changes of renal cortical Na+, K+-ATPase activity. Low doses of these esters (3 x 10(-11) mol/kg/min) increased activity of Na+, K+-ATPase whereas high doses (3 x 10(-9) mol/kg/min) decreased it. The changes in Na+, K+-ATPase activity induced by PDBu and PMA were prevented by staurosporine, a PKC inhibitor. 4Alpha phorbol didecanoate (4alpha PDD), phorbol ester which does not activate PKC had no effect on cortical Na+, K+-ATPase. PDBu and PMA did not change Na+, K+-ATPase activity in the renal medulla. The stimulatory effect of PDBu (3 x 10(-11) mol/kg/min) was neither mimicked by amphotericin B, a sodium ionophore nor blocked by amiloride, an inhibitor of Na+/H+-exchanger. The inhibitory effect of 3 x 10(-9) mol/kg/min PDBu was not mimicked by amiloride indicating that the observed effects of PKC stimulation are not secondary to alterations in intracellular sodium concentration. The inhibitory effect of PDBu was prevented by infusion of ethoxyresorufin, an inhibitor of cytochrome P450-dependent arachidonate metabolism. These results suggest that the inhibitory effect of PKC on renal cortical Na+, K+-ATPase is mediated by cytochrome P450-dependent arachidonate metabolites.

Reducing effect of atrial natriuretic factor on Na, K-ATPase activity in rat kidney.

This study was designed to examine the effect of the rat atrial extract (RAE) and synthetic rat ANF123-150 (rANF) on the renal Na, K-ATPase activity in Wistar anesthetized rats. Na, K-ATPase activity was assayed by measuring the amount of inorganic phosphate liberated from ATP. RAE from 40.3, 80.6 mg of tissue and rANF in the following doses: 0.043, 0.087, 0.173, 0.260 nM/kg/min reduced Na, K-ATPase activity by 59, 64 and 11, 34, 37, 45% respectively in the renal medulla but not in the cortex. It was associated with the increase in diuresis and natriuresis. Five and ten minutes after the end of rANF administration, Na, K-ATPase activity was decreased by 78 and 57% respectively, diuresis and natriuresis were significantly higher than the control. After fifteen minutes enzyme activity returned to normal, diuresis and natriuresis were increased. After thirty minutes there was a 37% increase in Na, K-ATPase activity but diuresis and natriuresis were still higher than control values. We conclude that the inhibition of Na, K-ATPase in the medulla of the rat kidney is one of the mechanisms of ANF action.

Arterial blood pressure measurement technique.

Arterial blood pressure (BP) measurements, which include invasive direct methods and noninvasive indirect methods, provide a picture of the hemodynamic status of the patient. Invasive BP methods measure pressure pulse wave amplitude; noninvasive methods rely on blood flow or arterial wall motion as a basis for the determination of BP values. To obtain the most accurate BP value, the clinician must identify which measurement variables in a specific clinical situation are most contributory to error and, if possible, use a method of measurement for which the sources of error are not parallel. Blood pressure values obtained by different methods cannot be compared without a thorough understanding of the user-related and instrumentation-related limitations associated with each BP measurement technique.

The clinical nurse specialist role in product research and development.

Think about the variety of products used each day in the critical care environment. They include everything from the most sophisticated monitors to the many disposable products. Most products function very well, but when they do not, do you wish you could talk to the person who designed that product? How can your input make medical products work better? The authors describe a career opportunity open to critical care nurses, that of a clinical nurse specialist for a medical products corporation, whose job it is to influence the design and quality of medical products.

[Effect of acute and chronic administration of L- thyroxine and methimazole on blood levels of tryptophane, serotonin and 5-hydroxyindoleacetic acid in plasma of rats]. / Wplyw krótkotrwalego oraz przewleklego podawania L-tyroksyny i metizolu na poziom tryptofanu, serotoniny i kwasu 5-hydroksyindolooctowego w osoczu krwi szczurów.

The effects of hyperthyreosis induced by the administration of thyroxine and hypothyreosis induced by the administration of methimazole on the levels of tryptophane, serotonin and 5-hydroxyindoleacetic acid in low-platelet blood plasma have been studied in Wistar rats. Thyroxine administration (120 micrograms/kg/24 h, intraperitoneally) lasting 7 days caused a decrease in serotonin concentration by 38 per cent. The level of this amine in rats receiving thyroxine during three months was elevated by almost three times. Tryptophane concentration did not change following thyroxine administration. Methimazole administration lasting 14 days (oral dose 15 mg/kg/24 h) caused an increase in tryptophane concentration by 34 per cent and in serotonin concentration by 24 per cent. Long-term hypothyreosis induced by methimazole administration lasting three months caused an 39 per cent increase in tryptophane and 38 per cent increase in serotonin concentration. Neither hyperthyreosis induced by thyroxine administration nor hypothyreosis induced by methimazole++ caused any changes in the concentration of 5-hydroxyindoleacetic acid. The importance of serotonin in pathogenesis of clinical symptoms accompanying the states of deficit or excess of thyroid hormones needs further elucidation.

[Vegetative nervous system's contribution to the development of stress induced gastric ulcers]. / Udzial wegetatywnego ukladu nerwowego w powstawaniu stresowych wrzodów zoladka.

A vegetative nervous system contribution to the development of stress-induced gastric ulcers has been investigated. The experiments involved male Wistar rats. Vegetative nervous system activity has been assessed with acetylcholine brain and stomach tissue levels and synthesis as well as adrenaline and noradrenaline levels in adrenals and gastric wall. The results have shown, that ulcerogenic effect of stress is accompanied by the increase in both cholinergic and adrenergic activities. Moreover, it has been shown, that markedly strong stimulation of the adrenergic system in some rats, together with pharmacologic activation of alpha-adrenergic receptors, inhibits the development of stress-induced gastric ulcers.