GABA exhibits depolarizing action in the immature neurons due to high intracellular activity of chloride ions. It is maintained by cation-chloride cotransporter NKCC1 which is present in immature brain. Bumetanide is a specific inhibitor of this cotransporter. We studied possible anticonvulsant activity of bumetanide in pentylenetetrazol-induced seizures in three age groups of rat pups (7, 12, and 18 days old). Pretreatment with bumetanide (0.2-1 mg/kg i.p.) resulted in dose-dependent decrease of incidence of the tonic phase of generalized tonicclonic seizures in 12-day-old rats only. No effect was observed in younger and older animals. Higher dose of bumetanide (2.5 mg/kg) did not affect tonic convulsions but, on the contrary, decreased latencies of generalized seizures in 12-day-old animals. Lack of marked anticonvulsant effect is probably due to relative maturity of neurons in the brainstem where the generator of generalized seizures is localized. Age- and dosespecific suppression of the tonic phase needs further analysis.
- MeSH
- antikonvulziva farmakologie MeSH
- bumetanid farmakologie MeSH
- epilepsie tonicko-klonická chemicky indukované metabolismus prevence a kontrola MeSH
- financování organizované MeSH
- GABA metabolismus MeSH
- inhibitory Na-K-Cl symportérů farmakologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- pentylentetrazol MeSH
- potkani Wistar MeSH
- reakční čas MeSH
- sodík-draslík-chloridové symportéry metabolismus účinky léků MeSH
- stárnutí MeSH
- věkové faktory MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- MeSH
- biologický transport fyziologie účinky léků MeSH
- bumetanid farmakologie MeSH
- cholesterol krev MeSH
- finanční podpora výzkumu jako téma MeSH
- hypertenze metabolismus MeSH
- krevní tlak genetika MeSH
- krysa rodu rattus MeSH
- kuchyňská sůl farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- MeSH
- bumetanid farmakologie MeSH
- chloridy antagonisté a inhibitory metabolismus MeSH
- hypoxie metabolismus MeSH
- krysa rodu rattus MeSH
- kyselina 4,4'-diisothiokyanostilben-2,2'-disulfonová farmakologie MeSH
- maternofetální výměna látek MeSH
- osmolární koncentrace MeSH
- placenta metabolismus MeSH
- těhotenství MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- MeSH
- bumetanid farmakologie MeSH
- draslík metabolismus MeSH
- erytrocyty metabolismus účinky léků MeSH
- hypertriglyceridemie krev patofyziologie MeSH
- krevní tlak genetika MeSH
- krysa rodu rattus MeSH
- ouabain farmakologie MeSH
- sodík metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
Red blood cell Na+ content as well as ouabain-resistant Na+ and Rb+ (K+) transport (susceptible or resistant to inhibition by loop diuretics) were determined in spontaneously hypertensive rats (SHR) and normotensive Brown Norway (BN) rats the erythrocytes of which were incubated in either saline or Mg(2+)-sucrose medium. Elevated ouabain-resistant Na+ net uptake contrasted with slightly decreased red blood cell Na+ content in SHR compared with BN rats. Acceleration of furosemide- and bumetanide-sensitive Na+ fluxes contributed to enhanced ouabain-resistant Na+ influx into SHR erythrocytes in saline medium, whereas higher furosemide- or bumetanide-resistant Na+ efflux caused greater ouabain-resistant Na+ efflux in Mg(2+)-sucrose medium. Furosemide- and bumetanide-resistant Rb+ leaks were augmented in SHR erythrocytes. The association of the disclosed ion transport alterations with blood pressure was examined in 20 recombinant inbred strains derived from F2 SHR x BN hybrids. Ouabain-resistant Na+ uptake as well as furosemide- and bumetanide-resistant Na+ inward leaks (but not red blood cell Na+ content or furosemide- and bumetanide-sensitive Na+ net uptake) cosegregated with systolic and pulse pressures but not diastolic pressure of the recombinant inbred strains. In contrast, neither ouabain-resistant Na+ efflux nor any component of ouabain-resistant Rb+ uptake correlated positively with blood pressure of the recombinant inbred strains. Increased ouabain-resistant Na+ influx was compensated for by accelerated ouabain-sensitive Na+ extrusion because red blood cell Na+ content was not elevated in the hypertensive strains. Thus, high cell Na+ turnover rates might be related to genetic hypertension if an altered Na+ inward leak would be less effectively compensated for in tissues involved in cardiovascular regulation.
- MeSH
- analýza rozptylu MeSH
- biologický transport MeSH
- bumetanid farmakologie MeSH
- draslík farmakokinetika MeSH
- erytrocyty * metabolismus MeSH
- furosemid farmakologie MeSH
- genetické markery MeSH
- hybridizace genetická MeSH
- hypertenze * patofyziologie MeSH
- krevní tlak genetika účinky léků MeSH
- krysa rodu rattus MeSH
- ouabain farmakologie MeSH
- potkani inbrední BN MeSH
- potkani inbrední SHR MeSH
- rubidium farmakokinetika MeSH
- sodík * farmakokinetika MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- bumetanid farmakologie MeSH
- erytrocyty metabolismus účinky léků MeSH
- furosemid farmakologie MeSH
- hypertenze chemicky indukované krev patofyziologie MeSH
- krysa rodu rattus MeSH
- ouabain farmakologie MeSH
- sodík dietní MeSH
- sodík krev MeSH
- techniky in vitro MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- ženské pohlaví MeSH
- zvířata MeSH
