Tissue distribution of tungsten in mice following oral exposure to sodium tungstate

Heavy metal tungsten alloys have replaced lead and depleted uranium in many munitions applications, due to public perception of these elements as environmentally unsafe. Tungsten materials left in the environment may become bioaccessible as tungstate, which might lead to population exposure through water and soil contamination. Although tungsten had been considered a relatively inert and toxicologically safe material, recent research findings have raised concerns about possible deleterious health effects after acute and chronic exposure to this metal. This investigation describes tissue distribution of tungsten in mice following oral exposure to sodium tungstate. Twenty-four 6-9 weeks-old C57BL/6 laboratory mice were exposed to different oral doses of sodium tungstate (0, 62.5, 125, and 200 mg/kg/d) for 28 days, and after one day, six organs were harvested for trace element analysis with inductively coupled plasma mass spectrometry (ICP-MS). Kidney, liver, colon, bone, brain, and spleen were analyzed by sector-field high-resolution ICP-MS. The results showed increasing tungsten levels in all organs with increased dose of exposure, with the highest concentration found in the bones and the lowest concentration found in brain tissue. Gender differences were noticed only in the spleen (higher concentration of tungsten in female animals), and increasing tungsten levels in this organ were correlated with increased iron levels, something that was not observed for any other organ or either of the two other metals analyzed (nickel and cobalt). These findings confirmed most of what has been published on tungsten tissue distribution; they also showed that the brain is relatively protected from oral exposure. Further studies are necessary to clarify the findings in splenic tissue, focusing on possible immunological effects of tungsten exposure.     

Cat carotid body chemosensory discharge (in vitro) is insensitive to charybdotoxin

Charybdotoxin (ChTX), a venom protein, suppresses Ca²⁺-activated K⁺ (K_Ca⁺) currents in the glomus cell of neonatal rat carotid body. If it works similarly for cat carotid body chemoreceptors, charybdotoxin is expected to stimulate the chemosensory discharge during normoxia, and particularly hypoxia and hypercapnia. We studied the effects of charybdotoxin (20–40 nM) in vitro (perfused/superfused) on the cat carotid chemosensory discharge, and simultaneously tissue PO₂ (PtiO₂), as a measure of positive control. ChTX (20 nM) only increased PtiO₂ and decreased carotid chemosensory discharge during hypoxia, indicating vasodilation. We conclude that K_Ca⁺ channels do not appear to play a significant role in chemotransduction in the cat carotid body.     

Relationship between sympathetic and phrenic nerve responses to peripheral chemoreflex in the cat

To test the hypothesis that peripheral chemoreflex effect on the preganglionic cervical sympathetic nerve (PSN) activity is entirely mediated by the central respiratory drive (CRD), as expressed in the phrenic nerve (PN) activity, we studied the relationship between PN and PSN activities under controlled conditions of carotid chemosensory excitation in the anesthetized cats. The cats were vagotomized, paralyzed and artificially ventilated. Tracheal pO2 and pCO2, systemic blood pressure, activities of single or a few PSN and PN fibers and a PN bundle were simultaneously recorded. The PSN preparations, which were responsive to hypoxia and showed PN rhythm, were selected for the study. Carotid chemoreceptor excitation, produced by hypoxia (end-tidal pO2 approximately equal to 50 Torr) or by sodium cyanide injection (50-100 micrograms, i.v.), elicited 3 types of responses: (1) the PSN discharged during the silent period of PN activity, although the PSN peak activity was still coupled to the PN peak activity, (2) PSN discharged only during PN activity, and (3) during the absence of PN discharge induced by hyperventilation hypocapnia, cyanide injection stimulated the PSN without PN activity. These observations suggest a model of chemoreflex control of sympathetic nerve activity which consists of two parts: one is dependent on PN activity and the other is not. Accordingly, all PSN chemoreflex responses may not be integrated with all inspiratory chemoreflexes.     

Acid-sensing by carotid body is inhibited by blockers of voltage-sensitive Ca channels

The membrane potential hypothesis that the responses to hypercapnia of carotid chemosensory activity is mediated by voltage-gated Ca²⁺ channels was investigated by measuring directly the chemosensory output from rat and cat carotid bodies, perfused and superfused in vitro. We found that the inorganic and organic blockers of voltage-gated Ca²⁺ channels suppressed the hypercapnic responses, thereby supporting the membrane potential hypothesis.