Ca2+ sensitization and Ca2+ entry in the control of blood pressure and adrenergic vasoconstriction in conscious Wistar-Kyoto and spontaneously hypertensive rats
Jazyk angličtina Země Nizozemsko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
PubMed
24107733
DOI
10.1097/hjh.0b013e328362adb3
PII: 00004872-201310000-00017
Knihovny.cz E-zdroje
- MeSH
- 1-(5-isochinolinsulfonyl)-2-methylpiperazin analogy a deriváty farmakologie MeSH
- 3-pyridinkarboxylová kyselina, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)fenyl)-, methyleste farmakologie MeSH
- adrenergní receptory metabolismus MeSH
- agonisté vápníkových kanálů farmakologie MeSH
- arteriae mesentericae účinky léků MeSH
- kinázy asociované s rho antagonisté a inhibitory metabolismus MeSH
- krevní tlak * MeSH
- krysa rodu Rattus MeSH
- nifedipin farmakologie MeSH
- noradrenalin farmakologie MeSH
- oxid dusnatý metabolismus MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- rhoA protein vázající GTP metabolismus MeSH
- teplota MeSH
- vápník metabolismus MeSH
- vápníkové kanály - typ L metabolismus MeSH
- vazokonstrikce účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- 1-(5-isochinolinsulfonyl)-2-methylpiperazin MeSH
- 3-pyridinkarboxylová kyselina, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)fenyl)-, methyleste MeSH
- adrenergní receptory MeSH
- agonisté vápníkových kanálů MeSH
- fasudil MeSH Prohlížeč
- kinázy asociované s rho MeSH
- nifedipin MeSH
- noradrenalin MeSH
- oxid dusnatý MeSH
- rhoA protein vázající GTP MeSH
- vápník MeSH
- vápníkové kanály - typ L MeSH
BACKGROUND: Calcium entry through nifedipine-sensitive L-type voltage-dependent calcium channels (L-VDCC) is augmented in spontaneously hypertensive rats (SHR) characterized by enhanced sympathetic vasoconstriction. However, the changes of calcium sensitization mediated by RhoA/Rho kinase pathway are less understood. METHODS AND RESULTS: The participation of calcium entry and calcium sensitization in the control of blood pressure (BP) and vascular contraction was studied in SHR and normotensive Wistar-Kyoto (WKY) rats. The acute administration of fasudil (Rho kinase inhibitor) caused BP decrease which lasted longer in SHR. Fasudil also attenuated adrenergic contraction in femoral or mesenteric arteries of WKY and SHR. BP reduction elicited by fasudil in WKY was more pronounced than that induced by L-VDCC blocker nifedipine (-33±2 vs. -15±3% of baseline BP, P<0.001), whereas both inhibitors were similarly effective in SHR (-36±4 vs. -41±2%). Fasudil pretreatment also attenuated BP elevation elicited by L-VDCC agonist BAY K8644 more in WKY than in SHR (-63±4 vs. -42±5%, P<0.001), indicating reduced calcium sensitization in SHR. Moreover, fasudil pretreatment shifted norepinephrine dose-response curves to the right more in WKY than in SHR. The additional nifedipine pretreatment shifted these curves further to the right but this shift was more pronounced in SHR than in WKY. Thus adrenergic vasoconstriction is more dependent on L-VDCC in SHR and on RhoA/Rho kinase pathway in WKY rats. CONCLUSION: Ca sensitization mediated by RhoA/Rho kinase pathway is attenuated in SHR compared with normotensive WKY rats. This might be a part of the compensation for enhanced Ca entry through L-VDCC in genetic hypertension.
Citace poskytuje Crossref.org
Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension
