Influence of the marine feeding area on the muscle and egg fatty-acid composition of Atlantic salmon Salmo salar spawners estimated from the scale stable isotopes.

Fatty acids in muscle tissue and eggs of female Atlantic salmon Salmo salar spawners were analysed to evaluate the dietary quality of their final feeding areas in the Baltic Sea. The final likely feeding area was identified by comparing stable carbon and nitrogen isotope composition of the outermost growth region (final annulus) of scales of returned S. salar with that of reference S. salar caught from different feeding areas. Some overlap of stable-isotope reference values among the three areas, in addition to prespawning fasting, decreased the ability of muscle tri-acylglycerols to discriminate the final likely feeding area and the area's dietary quality. Among three long-chained polyunsaturated fatty acids, docosahexaenoic acid (DHA; 22:6n-3), eicosapentaenoic acid (EPA; 20:5n-3) and arachidonic acid (ARA; 20:4n-6), the proportions of ARA in total lipids of spawning S. salar muscle and eggs showed a significant negative correlation with increasing probability of S. salar having returned from the Baltic Sea main basin (i.e. the Baltic Sea proper). The results suggest that ARA in muscle and eggs is the best dietary indicator for dietary characteristics of final marine feeding area dietary characteristics among S. salar in the Baltic Sea.

Elevated water temperature impairs fertilization and embryonic development of whitefish Coregonus lavaretus.

The adverse effects of high temperatures on the early life stages of anadromous whitefish Coregonus lavaretus were experimentally examined by assessing fertilization success, the percentage of developmental abnormalities, cumulative mortality and the rate of embryogenesis across a range of temperatures. Temperatures >or= 7 degrees C increased the proportion of unfertilized and abnormally dividing eggs, deformed embryos and consequent mortality. The higher the temperature, the more severe were the effects. When eggs were fertilized and constantly incubated at various temperatures, the effective level for 50% of the eggs and embryos (EL50) of temperature was 7.6 degrees C at the developmental stage when eye pigmentation was visible. Fewer developmental abnormalities and a lower cumulative mortality rate were observed when embryos were exposed to high temperatures from the later, gastrula stage, than from fertilization or the four-cell stage. Irrespective of retarded development in terms of day-degrees (i.e. the sum of daily mean temperatures), a high incubation temperature reduced the development time of C. lavaretus, leading to earlier hatching, and hatched fry were shorter than at the reference temperature of 4-5 degrees C. Global warming will particularly pose risks for stenothermic species such as C. lavaretus, with early life stages being especially susceptible. Thus, relatively small increases and fluctuations in river water temperatures during the spawning season of this anadromous species may have substantial negative impacts on its recruitment and population persistence.

Nitric oxide donor GEA 3162 inhibits endothelial cell-mediated oxidation of low density lipoprotein.

The effect of a nitric oxide (NO) donor GEA 3162 on the endothelial cell (EC)-mediated oxidation of low density lipoprotein (LDL) was studied. In comparison to LDL incubated with EC without GEA 3162, the presence of GEA 3162 inhibited LDL oxidation by EC, as indicated by the following findings. (a) The degradation rate of LDL in macrophages was reduced to control levels. (b) The electrophoretic mobility of LDL decreased in a dose-dependent manner. (c) The concentrations of thiobarbituric acid-reactive substances and hydroperoxide-derived hydroxy fatty acids were lower. (d) The breakdown of apolipoprotein B was reduced. The results indicate that GEA 3162 prevents EC-mediated oxidation of LDL.

Contractions induced by potassium-free solution and potassium relaxation in vascular smooth muscle of hypertensive and normotensive rats.

1. Vascular contractions induced by K(+)-free solution and relaxation responses following the return of K+ to the organ bath were studied in mesenteric arterial rings from spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) with particular focus on the role of vascular adrenergic nerve-endings and endothelium. 2. In endothelium-denuded rings the omission of K+ from the incubation medium resulted in gradual contractions, the rate of which was slower in SHR than WKY. Nifedipine (1 microM) inhibited the contractions more effectively in SHR than WKY. 3. Adrenergic denervation in vitro with 6-hydroxydopamine reduced the contractions induced by the K(+)-free medium in endothelium-denuded rings. The remaining contractions after denervation were markedly greater in SHR than WKY. 4. The presence of intact vascular endothelium attenuated the K(+)-free contractions in both strains, the attenuation being smaller in SHR than WKY. NG-nitro-L-arginine methyl ester (L-NAME, 0.1 mM) and methylene blue (10 microM), but not indomethacin (10 microM), abolished the attenuating effect of endothelium on the K(+)-free contractions. L-Arginine (1 mM) reversed the effect of L-NAME in WKY but not in SHR. 5. The re-addition of K+ after full K(+)-free contractions dose-dependently relaxed the rings. The rate of this K(+)-induced relaxation was significantly slower in SHR than WKY at all K+ concentrations (0.1-5.9 mM) studied, whether the endothelium or functioning adrenergic nerve-endings were present or not. Ouabain (1 mM) totally inhibited the K+ relaxation in SHR but only partially in WKY.6. Vascular smooth muscle contractions induced by high concentrations of potassium were comparable between the strains. The EC50 for noradrenaline-induced contractions was lower in SHR than WKY, but the maximal forces did not differ significantly.7. In conclusion, the contractile response in K+-free solution more clearly differentiates vascular rings from SHR and WKY than the responses induced by the classical contractile agents noradrenaline and high concentrations of potassium. The depressant effect of the presence of intact endothelium on the K+-free contractions, which was smaller in SHR than WKY, is mediated via the endothelium-derived relaxing factor. Neurotransmitter release from vascular adrenergic nerve-endings participates less in the K+-free contractile response in SHR than WKY. Moreover, the contractile response is more dependent on calcium entry through nifedipine-sensitive calcium channels in SHR than WKY. The greater K+-free contractions of denervated endothelium-denuded rings and the reduced K+ relaxation rate in SHR when compared to WKY suggest increased cell membrane permeability and decreased activity of vascular Na+, K+-ATPase, respectively, in this type of genetic hypertension.

Effects of P1 and P2Y purinoceptor antagonists on endothelium-dependent and -independent relaxations of rat mesenteric artery to GTP and guanosine.

1. Guanosine 5'-triphosphate (GTP) and guanosine can relax both endothelium-intact and -denuded arterial preparations. In the present work the P1 and P2Y purinoceptor antagonists, 8-phenyltheophylline and reactive blue 2, respectively, were used to study the mechanisms of relaxation responses induced by GTP, guanosine, adenosine 5'-triphosphate (ATP) and adenosine in noradrenaline-precontracted rat mesenteric artery rings. 2. GTP (10 microM-1mM) dose-dependently relaxed endothelium-intact mesenteric artery rings and also induced moderate relaxation responses in endothelium-denuded preparations. Pretreatment of the rings with 8-phenyltheophylline (10 microM) or reactive blue 2 (10 microM) did not attenuate the relaxant effect of GTP. 3. Guanosine (10 microM-1mM) relaxed both endothelium-intact and -denuded artery rings in a dose-dependent manner. The presence of 8-phenyltheophylline or reactive blue 2 had no effects on guanosine-induced relaxations. 4. ATP-induced (0.1 microM-0.1 mM) relaxation of endothelium-intact artery rings was attenuated by reactive blue 2 while 8-phenyltheophylline was ineffective. ATP also relaxed endothelium-denuded artery rings and this relaxation was inhibited by 8-phenyltheophylline, but not by reactive blue 2. 5. Adenosine-induced (10 microM-1 mM) relaxation of endothelium-intact and -denuded artery rings was attenuated by the presence of 8-phenyltheophylline, but not of reactive blue 2. 6. In conclusion, the endothelium-dependent and -independent relaxations of rat mesenteric arteries to GTP and guanosine are not mediated via P1 and P2Y purinoceptors. Therefore, these results support our previous suggestion on the presence of a novel guanine nucleotide-specific receptor, a putative PG receptor, on both endothelial and smooth muscle cells, which may participate in the regulation of arterial tone.

Inhibition by nitric oxide-donors of human polymorphonuclear leucocyte functions.

1. The study was designed to test the hypothesis that nitric oxide (NO)-releasing compounds increase guanosine 3':5'-cyclic monophosphate (cyclic GMP) production in human polymorphonuclear leucocytes (PMNs) and concomitantly inhibit PMN functions, i.e. leukotriene B4 (LTB4) synthesis, degranulation, chemotaxis and superoxide anion (O2-) release. The effects of two new NO-releasing compounds, GEA 3162 and GEA 5024 were compared to 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetyl-penicillamine (SNAP). 2. GEA 3162 and GEA 5024 (1-100 microM) inhibited Ca ionophore A23187-induced LTB4 and beta-glucuronidase release, chemotactic peptide FMLP-induced chemotaxis and opsonized zymosan-triggered chemiluminescence dose-dependently in human PMNs. SIN-1 and SNAP were weaker inhibitors. 3. Cellular cyclic GMP production was increased after exposure to NO-donors concomitantly with the inhibition of PMN functions. No alterations in the levels of adenosine 3':5'-cyclic monophosphate (cyclic AMP) were detected. 4. The results suggest that NO, possibly through increased cyclic GMP, inhibits the activation of human PMNs and may thus act as a local modulator in inflammatory processes.

Endothelium-dependent and -independent effects of exogenous ATP, adenosine, GTP and guanosine on vascular tone and cyclic nucleotide accumulation of rat mesenteric artery.

1. The effects of exogenous guanosine 5'-triphosphate (GTP) and guanosine on vascular tone and cyclic nucleotide accumulation of noradrenaline-precontracted endothelium-intact and endothelium-denuded rat mesenteric artery rings were compared with the effects of the known purinoceptor agonists adenosine 5'-triphosphate (ATP) and adenosine. 2. GTP (10 microM-1 mM) dose-dependently relaxed endothelium-intact mesenteric artery rings by producing a rapid initial response followed by sustained relaxation resembling the relaxant response to acetylcholine. GTP also slightly relaxed endothelium-denuded artery rings. The acetylcholine- and GTP-induced relaxations of endothelium-intact rings were attenuated by NG-nitro L-arginine methyl ester (L-NAME, 330 microM) which attenuation was reversed with L-arginine (1 mM). 3. Guanosine (10 microM-1 mM) relaxed both endothelium-intact and -denuded artery rings in a dose-dependent manner. The relaxations were more pronounced in endothelium-intact preparations and were only slightly attenuated by L-NAME (330 microM). 4. ATP (1 microM-1 mM) and adenosine (10 microM-1 mM) dose-dependently relaxed endothelium-intact and -denuded artery rings. The responses were more pronounced in endothelium-intact vascular preparations. 5. GTP (100 microM) and guanosine (100 microM) increased guanosine 3':5'-cyclic monophosphate (cyclic GMP) accumulation in both endothelium-intact and -denuded artery rings corresponding to the relaxations observed. The concentrations of adenosine 3':5'-cyclic monophosphate (cyclic AMP) were not affected. 6. ATP (100 microM) increased cyclic GMP concentration of endothelium-intact artery rings. The concentrations of cyclic AMP were not affected by ATP (100 microM) and adenosine (100 microM) in endothelium-intact and -denuded vascular preparations.7. These results provide evidence that exogenous GTP and guanosine relax precontracted endothelium-intact and -denuded rat mesenteric artery rings by increasing cyclic GMP accumulation. The response to GTP of endothelium-intact rings can mainly be explained by the release of endothelium-derived relaxing factor (EDRF), but that of guanosine is only partly due to EDRF, and is a combination of endothelium-dependent and -independent effects. The endothelium-independent response of GTP and guanosine is a direct, unknown effect on smooth muscle and guanylate cyclase.

Nitric oxide-donating properties of mesoionic 3-aryl substituted oxatriazole-5-imine derivatives.

1. The nitric oxide (NO)-releasing properties of two new mesoionic 3-aryl substituted oxatriazole-5-imine derivatives (GEA 3162 and GEA 3175) were characterized and compared with the known NO-donors 3-morpholino-sydnonimine (SIN-1) and S-nitroso-N-acetylpenicillamine (SNAP). 2. GEA 3162, GEA 3175, SIN-1 and SNAP inhibited adenosine 5'-diphosphate-induced platelet aggregation (IC50 values 0.18, 0.39, 3.73 and 2.12 microM, respectively). All four compounds induced a dose-dependent and more than 4 fold increase in cyclic GMP in platelets. The increase in cyclic GMP concentration was potentiated more than 1.5 fold by a phosphodiesterase inhibitor, zaprinast (10 microM) and inhibited 38-97% by oxyhaemoglobin (10-45 microM). 3. All of the four compounds studied converted oxyhaemoglobin to methaemoglobin and formed a paramagnetic NO-haemoglobin complex. All but GEA 3175 formed nitrite and nitrate in phosphate buffer. During a 40 min incubation, GEA 3162, SIN-1 and SNAP (100 microM) produced 50-70 microM NO2- + NO3- as determined by high performance liquid chromatography. The release of NO and NO2 by GEA 3175 was increased 140 fold in the presence of human plasma (0.14 and 19.7 ppb in the absence and presence of 1% human plasma, respectively) as analyzed by ozone chemiluminescence. 4. The results suggest that the mesoionic 3-aryl substituted oxatriazole-5-imine derivatives GEA 3162 and GEA 3175 as well as SIN-1 and SNAP release nitric oxide.

Induction of beta-2-microglobulin release in vitro by chronic lymphocytic leukaemia cells: relation to total protein synthesis.

The in vitro production of beta2-M by B-CLL cells from 27 patients was investigated. In all cases, low spontaneous beta2-M release was observed. The production of beta2-M was enhanced to various extents when induced with 13 different stimulants and their combinations including IL-2, TNFalpha, SAC and TPA. Beta2-M release was 3.8-fold (range from 1.9 to 9.2-fold) in cultures stimulated with TPA (10 ng/ml), compared with the spontaneous release, and even faster if TNFalpha or IL-2 were added. A strong correlation was revealed between beta2-M production and the total protein synthesis of leukaemic cells when the latter was assessed using 14C-L-leucine incorporation. Hence, both beta2-M release and leucine incorporation are promising activation markers for CLL B-lymphocytes.

Evaluation of the new Behring Nephelometer in the measurement of M proteins.

The Behring Nephelometer is a new automatic analyzer designed for the measurement of specific proteins. The authors evaluated the nephelometer in the determination of M proteins as compared with immunodiffusion and cellulose acetate electrophoresis. In addition, the effects of sample dilution and antigen excess on the nephelometric measurement of M proteins were studied in 24 patient samples containing a single monoclonal IgG, IgA, or IgM M component. Immunodiffusion cannot be recommended for the determination of M proteins. Nephelometry and protein electrophoresis gave similar results with few exceptions. Sera with immunoglobulin monomer-oligomer pairs involve difficulties in serum electrophoresis. In certain cases, special care must be taken to adjust the nephelometric measurement of the M protein to the most accurate part of the calibration curve. All in all, the new Behring Nephelometer proved precise and reliable in M protein determination without risk of antigen excess.

Inhibition of human lymphocyte proliferation by nitric oxide-releasing oxatriazole derivatives.

The effects of novel nitric oxide (NO)-releasing oxatriazole derivatives GEA 3162 and GEA 3175 were studied on cell proliferation and cGMP synthesis in human peripheral blood mononuclear cells stimulated with a lectin mitogen concanavalin A. GEA 3162 (1-30 microM) and GEA 3175 (3-30 microM) inhibited mononuclear cell proliferation in a dose-dependent manner being more potent than the earlier known NO-donor S-nitroso-N-acetylpenicillamine. The inhibitory action was more pronounced when submaximally stimulating concentrations of concanavalin A (0.1 and 1 microg/ml) were used and no inhibition was seen when concanavalin A concentrations were increased up to 10 microg/ml. The antiproliferative concentrations of GEA 3162, GEA 3175 and S-nitroso-N-acetylpenicillamine induced a rapid and transient increase in cGMP production in mononuclear cells cultured in the presence of concanavalin A. Both the antiproliferative action and the increased cGMP production were attenuated when red blood cells were added into the cultures indicating that NO is responsible for both of these actions. An analogue of cGMP, 8-bromo-cGMP (0.1-3 mM) reduced concanavalin A-induced proliferation in a dose-dependent manner suggesting that cGMP may be involved in the antiproliferative action of NO-donors. NO-releasing compounds have immunosuppressive actions which offer therapeutic possibilities and should be kept in mind as potential adverse events when these compounds are used in other indications.

Effects of cysteine and nitroglycerin on bovine heart guanylate cyclase and on tissue cyclic GMP and lactate of rat atria.

The effects of thiols on guanylate cyclase activation by nitroglycerin were studied in bovine heart and the effects of cysteinee and nitroglycerin on the tissue levels of cyclic GMP and lactate were studied in beating rat atria. Cysteine (2.5 X 10(-3) M) together with nitroglycerin (1 X 10(-3) M), increased 15-fold the activity of guanylate cyclase. In hypoxia, nitroglycerin (1 X 10(-3) M) together with cystein (5 X 10(-3) M) increased cyclic GMP and decreased the tissue lactate level. It is concluded that cysteine potentiates the effect of nitroglycerin on cyclic GMP formation even in integrated cell systems with an intact physiological function.

Inhibition of human neutrophil function by tolfenamic acid involves inhibition of Ca2+ influx.

The present work was designed to study the pharmacological control of the receptor-mediated activation of human neutrophils by tolfenamic acid (2(-)[(3-chloro-2-methylphenyl)-amino]benzoic acid). Tolfenamic acid inhibited in a concentration-dependent manner the degranulation response and Ca2+ influx in neutrophils activated either by the chemotactic peptide fMLP (N-formyl-methionyl-leucylphenylalanine) or Ca2+ ionophore A23187 (calcimycin). When fMLP was used to activate neutrophils, tolfenamic acid (30 microM) reduced Ca2+ influx by 50% and degranulation by 20%. A23187-triggered Ca2+ influx and degranulation were inhibited by 60% and 40%, respectively, by 30 microM tolfenamic acid. Tolfenamic acid did not inhibit the release of Ca2+ from intracellular stores induced either by fMLP or A23187. To confirm the inhibition of receptor-mediated cation influx by tolfenamic acid, the agonist induced Mn2+ influx was studied in Ca2+ free medium. Tolfenamic acid (10-30 microM) reduced fMLP-stimulated Mn2+ influx in neutrophils in a concentration-dependent manner. The simultaneous Ca2+ release from intracellular stores was not affected. Protein kinase C activity in sonicated human neutrophils and the purified enzyme from rat brain were inhibited by the protein kinase inhibitor H-7 (1-(5-isoquinolinylsulfonyl)-2-methylpiperazine) but not by tolfenamic acid. Both failed to inhibit neutrophil degranulation induced by phorbol myristate acetate, a protein kinase C activator. Tolfenamic acid (100 microM) increased the cellular cAMP levels up to 1.3-fold in the presence of the phosphodiesterase inhibitor 3-isobutyl-1-methylxanthine. No effects on cellular cGMP levels were found.(ABSTRACT TRUNCATED AT 250 WORDS)

L-cysteine augments the vasorelaxation induced by sodium nitrite and SIN-1 but not that due to acetylcholine.

The effects of 1 mM L-cysteine on sodium nitrite-, 3-morpholinosydnonimine (SIN-1)- and acetylcholine-induced relaxation and cyclic GMP accumulation were studied in isolated noradrenaline-precontracted rat mesenteric arterial rings. L-Cysteine augmented the relaxation and cyclic GMP increase induced by sodium nitrate and SIN-1 but not those induced by acetylcholine. The effects of L-cysteine on relaxation were independent of the presence of intact endothelium. The results suggest that L-cysteine protects exogenously released nitric oxide.

Mycobacterium tuberculosis complex is not detected by DNA amplification assay in sputum specimens of patients with lung scars due to past pulmonary tuberculosis.

OBJECTIVE: To evaluate detection of false-positive sputum amplification assay results in former tuberculosis patients with residual pulmonary scars. DESIGN: A total of 268 sputum specimens from 25 war veterans with tuberculosis during 1940-1959, without adequate chemotherapy, and 19 subjects effectively treated for cavitary tuberculosis during 1980-1993 were tested by smear, culture and DNA amplification, as were 34 controls with no history of tuberculosis or pulmonary scars. RESULTS: No active tuberculosis cases were identified. All specimens were negative on DNA amplification and smear. Eight specimens from six subjects were positive on culture, revealing atypical mycobacteria. CONCLUSION: No genetic Mycobacterium tuberculosis material in sputum specimens of subjects with residual lesions of pulmonary tuberculosis and no false-positive amplification results were detected.

Normal CSF neuron-specific enolase and S-100 protein levels in patients with recent non-complicated tonic-clonic seizures.

PURPOSE: Increased concentrations of the nervous-system-specific proteins neuron-specific enolase (NSE) and S-100 protein (S-100) have been measured with lesions in the CNS. Elevated levels of serum NSE (s-NSE) have been found in status epilepticus, but also after single epileptic seizures. Because larger studies addressing cerebrospinal fluid (CSF) levels of NSE or S-100 have not been performed, we measured CSF NSE and S-100 after tonic-clonic seizures to search for evidence of neuronal and glial damage. METHODS: 22 consecutive patients with single, previously undiagnosed and untreated tonic-clonic seizures were studied. Serum and CSF samples were collected within 24 h after seizure. 18 serum and CSF samples were measured from a control group. RESULTS: The mean CSF NSE was 8.9 ng/ml (range 0-28 ng/ml) and s-NSE 8.2 ng/ml (range 5-15 ng/ml) in the patient group. The mean concentrations in the control group were 13.1 ng/ml (range 3-24 ng/ml) and 8.0 ng/ml (range 5-12 ng/ml) respectively. The mean CSF S-100 was 3.17 microg/l (range 1.45-7.02 microg/l) and serum S-100 0.05 microg/l (range 0-0.32 microg/l), and in controls 3.19 microg/l (range 1.52-5.13 microg/l) and 0.08 microg/l (range 0-0.28 microg/l). CONCLUSION: There were no significant differences between the mean concentrations of NSE or S-100 in CSF and serum between the epileptic group and controls. These results do not confirm the previous observation of elevated NSE-levels after tonic-clonic seizures, which argues against neuronal or glial damage after uncomplicated tonic-clonic seizures in unmedicated patients.

8-Bromo cyclic GMP inhibits NADH and lactate accumulation in hypoxic rat atria.

The effects of 8-bromo-cGMP on tissue lactate and NADH levels were studied under conditions of high oxygen saturation (95-100%) and hypoxia (50%) in spontaneously beating rat atria. The induction of hypoxia caused a rapid decline in contractility with a simultaneous increase in tissue lactate and NADH. 8-bromo-cGMP (10(-4) mol/l) prevented the accumulation of lactate occurring during hypoxia. It also lowered the level of lactate during high oxygen saturation. Furthermore, 8-bromo-cGMP inhibited the hypoxia-induced increase in NADH and lowered the level of NADH in high oxygen saturation. 8-bromo-cGMP did not affect contractility or heart rate during hypoxia. It is concluded that cGMP may influence the redox-state and metabolism in a direction which is beneficial for the hypoxic myocyte. It is also suggested that antianginal nitro compounds which enhance the level of cGMP might exert an effect similar to that of 8-bromo-cGMP.

Effect of surgical stress on the erythrocyte insulin receptor.

The aim of this study was to investigate whether surgical trauma causes changes in insulin receptors which may have significance on the causation of post-traumatic insulin resistance. Twenty-four patients scheduled for lumbar intervertebral disc operations or thoracotomy were investigated. In patients who did not receive glucose during operation blood glucose and plasma insulin concentrations did not change but lipolysis was induced as indicated by the increase of serum free fatty acids concentration. Glucose infusion (5% w/v) caused a hyperglycaemic and hyperinsulaenemic response without lipolysis. In patients not receiving a glucose load the number of insulin receptors on erythrocyte measured 4 h postoperatively increased from the preoperative values and the affinity of the receptors to insulin in physiological concentration range increased. In patients with glucose load the number of receptors decreased and receptor affinity to insulin at physiological concentration decreased. The results suggest that in patients receiving a glucose load the receptor changes indicate the perioperative development of insulin resistance at receptor level.

The effects of cyclic AMP and cyclic GMP on redox state and energy state in hypoxic rat atria.

The effects of 8-bromo-cAMP (10(-4)M) and 8-bromo-cGMP (10(-4)M) on tissue lactate, NADH, creatine phosphate (CP), ATP, ADP and AMP were studied in hypoxic (50% oxygen saturation) spontaneously beating rat atria. CP/ATP ratio and energy charge (EC) were also calculated. In hypoxic rat atria there was a significant increase in tissue lactate, NADH, ADP and AMP and a decrease in CP, CP/ATP ratio and EC. 8-bromo-cGMP abolished these hypoxia-induced changes. The levels of lactate and NADH decreased and those of CP, ATP, ADP and EC increased after administration of 8-bromo-cGMP. 8-bromo-cAMP increased the level of lactate during hypoxia, but did not affect the other hypoxia-induced changes. The present work indicates that cyclic GMP can change the redox state and energy state in a more favourable direction for the hypoxic rat heart.

Plasma ANP and cyclic GMP after physical exercise in patients with mitral valve disease and in healthy subjects.

Plasma levels of both atrial natriuretic peptide (ANP) and cyclic GMP are elevated in patients with various heart diseases as compared to healthy subjects. In this study patients with advanced mitral valve disease (Group A) and healthy subjects (Group B) were exposed to symptom-limited upright stepwise physical exercise on a cycle ergometer. Concentrations of ANP and cyclic GMP were measured in plasma at rest (20 min in supine position) or 5 min after physical exercise by specific radioimmunoassays. Here we show that short dynamic exercise caused a significant increase in plasma levels of ANP and cyclic GMP, in both groups. In Group A strong correlation between plasma ANP and cyclic GMP was found at rest (r = 0.91, P < 0.001, n = 11) and after physical exercise (r = 0.85, P < 0.001, n = 11). In contrast, there was no correlation between plasma concentrations of ANP and cyclic GMP in Group B at rest (r = -0.16, P > 0.05, n = 10) or after exercise loading (r = 0.14, P > 0.05, n = 10). Absolute increases in circulating levels of both substances were not found to correlate in either group. These data suggest that exercise-induced elevations in plasma cyclic GMP may be due not only to ANP release but also to an as yet undetermined factor, possibly EDRF/NO.