Serotonin reuptake inhibitors and cardiovascular diseases: a platelet connection

Selective serotonin reuptake inhibitors (SSRIs) are a heterogeneous group of new antidepressants that cause a well documented acquired but reversible serotonin deficiency in blood platelets. Platelets are small, anucleate cells and are the only blood cells specialized in storing peripheral serotonin. Platelets are also an integral part of the hemostatic process that is initiated during pathologic thrombus formation in cardiovascular diseases. Serotonin release from platelets is important for functional hemostasis as indicated by congenital diseases with serotonin-deficient platelets that can lead to life-threatening bleeding problems. The postulate that SSRIs should have an impact on cardiovascular diseases is therefore well founded. Cardiovascular effects of SSRIs have indeed been shown in a number of studies investigating the effect of SSRIs in patients with psychosomatic comorbidity. SSRIs reduce the incidence of recurrent myocardial infarction (MI) in patients suffering from post-MI depression. In addition, SSRIs inhibit tight clot formation of platelets in vitro, which points to a direct anti-thrombotic or pro-fibrinolytic effect of SSRIs.Received 16 June 2004; received after revision 9 September 2004; accepted 23 September 2004     

Serotonin and 5-hydroxyindoleacetic acid concentrations in individual hypothalamic nuclei and other brain areas of rat

Summary Serotonin and 5-hydroxyindoleacetic acid (5-HIAA) were measured in individual nuclei of rat hypothalamus and other brain areas using HPLC with electrochemical detection. 5-HIAA levels were first demonstrated in hypothalamic and some discrete brain areas. The 5-HIAA/5-HT ratio was highest in the n. caudatus putamen, high in the n. ventromedialis and lowest in the n. suprachiasmaticus.     

Influence of diet on plasma tryptophan and brain serotonin levels in mice

Summary Groups of mice were maintained for up to 78 weeks on tryptophan restricted, protein restricted and control diets. Plasma tryptophan levels were significantly reduced by both forms of dietary restriction. Brain serotonin levels were significantly reduced only in mice on the tryptophan restricted diet, but not for mice on the protein restricted diet. The protein-restricted diet contains less of the large neutral amino acids which compete with tryptophan to enter the brain. It is known that protein restriction and tryptophan restriction extend lifespan. The results presented here suggest that extension of lifespan and lowering of brain serotonin are not related.     

The significance of temperature and barometric pressure changes for the snow surface activity ofIsotoma hiemalis (Collembola)

Summary Temperature is limiting for the snow surface activity ofIsotoma hiemalis: values below a threshold of –2.5° to –3°C are avoided. Changing barometric pressure leads to increased surface activity, thus being responsible for mass appearances. These experiments provide the first evidence for sensitivity to and reaction to barometric pressure changes in insects.The financial support by the Swiss National Science Foundation is highly acknowledged. I thank W. Matthey for the unpublished data onGerris remigis.     

Serotonin is localized in endothelial cells of coronary arteries and released during hypoxia: A possible new mechanism for hypoxia-induced vasodilatation of the rat heart

Summary In this report we demonstrate the immunocytochemical localization of serotonin in endothelial cells of rat coronary vessels and a significant increase in the release of serotonin into the perfusate of Langendorff rat heart preparations during hypoxia. It is suggested that serotonin, localized in endothelial cells, is released during hypoxia and could provide part of a pathophysiological mechanism for vasodilatation to protect the heart from damage due to hypoxia.This research was supported by the British Heart Foundation and the excellent technical assistance of Jon Bokor is gratefully acknowledged.     

Effects of pressure on oxygen consumption in cottid fish from Lake Baikal

Summary Rates of oxygen consumption in shallow dwelling cottid fish from Lake Baikal were unaffected by a change in pressure from 11 to 51 ata. The metabolic rate of deep cottids decreased by 72% when the pressure was decreased by 50% from that corresponding to habitat depth. Recovery from decreased pressures was incomplete in deep fish, suggesting that measurements of in deep dwelling fish in the literature may underestimate actual rates.Acknowledgments. Thanks are due to the US and USSR Academies of Sciences and the crew of the Titov. Support was provided by grants from The National Geographic Society, The George Baker Trust, The Max and Victoria Dreyfus Foundation, and The Griffis Foundation, Inc.     

The role of muscle in determining growth and size in teleost fish

Summary Rapid growth to large size in fish results from a sustained recruitment of new fibres into their axial series of myomeres. Cessation of recruitment at a small fish size leads to slow growth and a small final size of the fish. Fibre growth dynamics of fishes evidently govern growth and size through fibres' surface area to length ratios, which control their nutrient assimilation rates.     

Effects of early undernutrition and subsequent rehabilitation on acetylcholine levels in rat brain

Summary Early undernutrition, induced by feeding mothers a low protein (5%) diet during gestation and/or lactation, resulted in significant deficits in acetylcholine concentration in the rat brain, and these deficits were reversed by subsequent dietary rehabilitation.This research was partly supported by Nutrition Society of India Grant-in-Aid Award (79/60) to Dr A.B. Kulkarni. We would like to thank Dr A.J. Baxi for valuable discussions throughout the course of these studies.     

l-DOPA administration to neonate chicks: Effects on behavior and levels of brain biogenic amines

Zusammenfassung Nachweis, dass bei Küken die i.v. Injektion vonl-Dopa (100 mg/kg) eine sofortige Überaktivität herbeiführt. Nach 10 min wurde im Gehirn eine Verminderung des Serotoningehaltes (14%) und eine Erhöhung des Dopamingehaltes (12fach) festgestellt, während Adrenalin, Noradrenalin und Histamin unverändert blieben.

---

---

The author (JPH) was supported in part by a National Science Foundation Predoctoral Traineeship.     

Effects of photoperiod,temperature and testosterone-treatment on plasma T3 and T4 levels in the Djungarian hamster,Phodopus sungorus

Summary The effects of photoperiod, temperature and testosterone treatment on plasma T₃ and T₄ levels were investigated in the Djungarian hamster. Plasma T₃ level was affected by temperature (25°C<7°C) but not by photoperiod. Plasma T₄ level was affected by photoperiod (short day < long day) at 25°C. Administration of testosterone increased plasma T₄ level under short photoperiod at 25°C. Thus, higher plasma T₄ level under long photoperiod at 25°C might be induced by testosterone.     

Pressure acclimation of the eel and liver membrane composition

Homeoviscous adaptation of membrane fluidity is known to exist in fish living at great depths. Is this adaptation also present in fish living near the surface but experimentally acclimated to high pressure? The composition of mitochondria-rich fractions extracted from the livers of eels acclimated for 15 days at 101 ATA was determined. The results show that pressure induced a significant increase (+100%) of total phospholipids (PL) and cholesterol without a change in their ratio. The increase of PL content was accompanied by a decrease in phosphatidylcholine in favour of phosphatidyl ethanolamine which, due to its preference for the H₁₁ form, is able to compensate for the loss in fluidity induced by pressure.     

Effects of temperature on K, Na and water movements in isolated hepatocytes]

Isolated hepatocytes incubated at 1 degrees C loss K, gain Na and water. Rewarming results in a transient increase in K and Na permeabilities. These are insensitive to quinine, suggesting that they are not caused by an intracellular Ca accumulation.     

Effects of lithium chloride on peripheral acetylcholine release and brain acetylcholine levels in the guinea-pig

Summary Lithium chloride administered acutely or chronically to guinea-pigs had no effect on brain level of acetylcholine or on peripheral release of acetylcholine from longitudinal muscle of the ileum. The results suggest differences between in vitro and in vivo action of lithium.To whom correspondence should be addressed.     

Rate of tryptophan hydroxylation in vivo in brain nuclei of genetically hypertensive rats of the Lyon strain

Summary The rate of tryptophan hydroxylation in vivo is unaltered in brain areas of 5, 9 and 21 week-old Lyon genetically Hypertensive (LH) rats as compared to both Lyon Normotensive (LN) and Low Blood Pressure (LL) rats, except for a decrease in the C1 area of the medulla oblongata in 9 week-old animals.Acknowledgment. The authors wish to thank Dr M.F. Belin, Dr J.F. Pujol and Mrs J. Sacquet for their help during this study. This work was supported by the Fondation pour la Recherche Médicale Française and the C.N.R.S.     

Effects of lithium chloride on peripheral acetylcholine release and brain acetylcholine levels in the guinea-pig.

Lithium chloride administered acutely or chronically to guinea-pigs had no effect on brain level of acetylcholine or on peripheral release of acetylcholine from longitudinal muscle of the ileum. The results suggest differences between in vitro and in vivo action of lithium.     

Possible involvement of indolamines in the glycogenic effect of the convulsant methionine sulfoximine in rat brain

Summary The aim of the present investigation was to look for the mechanisms causing disturbances in carbohydrate metabolism during the action of the epileptogenic agent methionine sulfoximine The levels of glucose, glycogen, and indolamines were measured in seven different regions of rat brain. Methionine sulfoximine induced a decrease in serotonin level which was roughly dose-dependent. There were no obvious, changes in tryptophan and 5-hydroxyindoleacetic levels in any area. Methionine sulfoximine induced the known increase in glucose and glycogen levels. The direct precursor of serotonin, 5-hydroxytryptophan, and benserazide (a decarboxylase inhibitor) were then injected into rats in association with methionine sulfoximine. In this case, methionine sulfoximine failed to induce seizures. Moreover, the serotonin level was unchanged and the carbohydrate content did not significantly increase. There was only a rise in 5-hydroxyindoleacetic acid level. This work shows a striking parallelism between serotonin decrease and glycogen increase.     

Pre- and postnatal lead exposure affects the serotonergic system in the immature rat brain

Summary The effect of pre- and postnatal lead exposure on the development of the serotonergic system in striatum and brain stem was investigated. Serotonin and its metabolite 5-HIAA where determined by HPLC-EC. A significant decrease of 5-HT was detected in the brain stem at postnatal day 28. At both days 6 and 28 postnatal, 5-HIAA was reduced in striatum and brain stem. The results provide support to the hypothesis that developing 5-HT neurons are sensitive to relatively low levels of lead exposure.