" alfa2delta ligand" . . "hypertension, alfa2delta ligand, gabapentin, calcium influx, L type of voltage-dependent calcium channels, sympathetic nervous system"@en . . . . . . . " gabapentin" . . "2014-04-07+02:00"^^ . . "2015-02-09+01:00"^^ . . "1"^^ . "0"^^ . " L type of voltage-dependent calcium channels" . "0"^^ . "hypertension" . "Alfa2delta pomocn\u00E1 podjednotka nap\u011B\u0165ov\u011B z\u00E1visl\u00FDch v\u00E1pn\u00EDkov\u00FDch kan\u00E1l\u016F jako nov\u00FD terapeutick\u00FD c\u00EDl p\u0159i l\u00E9\u010Db\u011B hypertenze" . . "0"^^ . . . . . "2016-12-31+01:00"^^ . " calcium influx" . "http://www.isvav.cz/projectDetail.do?rowId=GP14-16225P"^^ . "2014-01-01+01:00"^^ . "0"^^ . "GP14-16225P" . . "Sou\u010Dasn\u00FD v\u00FDvoj antihypertenziv se zam\u011B\u0159uje na ovlivn\u011Bn\u00ED z\u00E1kladn\u00EDch zm\u011Bn, kter\u00E9 hypertenzi zp\u016Fsobuj\u00ED. K tomu je t\u0159eba d\u016Fkladn\u00E9ho pochopen\u00ED molekul\u00E1rn\u00ED patogeneze onemocn\u011Bn\u00ED. Hlavn\u00EDmi abnormalitami, kter\u00E9 byly u spont\u00E1nn\u011B hypertenzn\u00EDch potkan\u016F (SHR) pozorov\u00E1ny, jsou hyperaktivita sympatick\u00E9ho nervov\u00E9ho syst\u00E9mu (SNS) a zv\u00FD\u0161en\u00FD influx v\u00E1pn\u00EDku do bun\u011Bk hladk\u00E9ho svalu c\u00E9v (VSMC). Nap\u011B\u0165ov\u011B z\u00E1visl\u00E9 v\u00E1pn\u00EDkov\u00E9 kan\u00E1ly (VDCC) hraj\u00ED kl\u00ED\u010Dovou roli v obou procesech, tj. ve zv\u00FD\u0161en\u00ED sympatick\u00E9 neurotransmise i v zes\u00EDlen\u00ED c\u00E9vn\u00ED kontrakce. Vazba ligandu \u03B12\u03B4 podjednotek t\u011Bchto kan\u00E1l\u016F vede k poklesu po\u010Dtu povrchov\u011B lokalizovan\u00FDch VDCC a tedy i k poklesu v\u00E1pn\u00EDkov\u00E9ho influxu. C\u00EDlem tohoto projektu je a) analyzovat \u00FA\u010Dinky \u03B12\u03B4 ligandu na krevn\u00ED tlak (TK) u SHR, b) studovat molekul\u00E1rn\u00ED mechanismy \u03B12\u03B4 ligandu ve vztahu k hyperaktivit\u011B SNS resp. zm\u011Bn\u011B v\u00E1pn\u00EDkov\u00E9ho influxu do VSMC a c) vyhodnotit \u00FA\u010Dinek \u03B12\u03B4 ligandu na TK u jin\u00FDch forem hypertenze (k soli senzitivn\u00ED Dahlovi, NO-deficientn\u00ED nebo Ren2 transgenn\u00ED potkani). Regulace povrchov\u00E9 exprese VDCC \u03B12\u03B4 ligandem m\u016F\u017Ee b\u00FDt novou strategi\u00ED pro l\u00E9\u010Dbu hypertenze." . "Alpha2delta auxiliary subunit of voltage-dependent Ca2+ channels as a novel therapeutic target for the treatment of hypertension"@en . "The development of antihypertensive drugs is attempting to affect causal changes leading to hypertension. To accomplish this aim, detailed understanding of molecular pathogenesis of the disease is necessary. The major abnormalities observed in spontaneously hypertensive rats (SHR) are hyperactivity of sympathetic nervous system (SNS) and elevated calcium current in vascular smooth muscle cells (VSMC). Voltage-dependent calcium channels (VDCC) play an important role in both increased sympathetic neurotransmission and enhanced vascular contraction. Ligand of \u03B12\u03B4 subunits of VDCC reduces surface localization of these channels and hence calcium current. The aims of our project are a) to analyze the effects of \u03B12\u03B4 ligand on blood pressure (BP) in SHR, b) to study molecular mechanisms of its effect related to hyperactivity of SNS and/or altered calcium current in VSMC and c) to evaluate its BP effect in other forms of hypertension (salt-sensitive Dahl, NO deficient or Ren2 transgenic rats). Reduction of VDCC trafficking by \u03B12\u03B4 ligand could be a novel strategy for treatment of hypertension."@en . .