Ca2+ sensitization and Ca2+ entry in the control of blood pressure and adrenergic vasoconstriction in conscious Wistar-Kyoto and spontaneously hypertensive rats
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
PubMed
24107733
DOI
10.1097/hjh.0b013e328362adb3
PII: 00004872-201310000-00017
Knihovny.cz E-resources
- MeSH
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine analogs & derivatives pharmacology MeSH
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester pharmacology MeSH
- Receptors, Adrenergic metabolism MeSH
- Calcium Channel Agonists pharmacology MeSH
- Mesenteric Arteries drug effects MeSH
- rho-Associated Kinases antagonists & inhibitors metabolism MeSH
- Blood Pressure * MeSH
- Rats MeSH
- Nifedipine pharmacology MeSH
- Norepinephrine pharmacology MeSH
- Nitric Oxide metabolism MeSH
- Rats, Inbred SHR MeSH
- Rats, Inbred WKY MeSH
- rhoA GTP-Binding Protein metabolism MeSH
- Temperature MeSH
- Calcium metabolism MeSH
- Calcium Channels, L-Type metabolism MeSH
- Vasoconstriction drug effects MeSH
- Dose-Response Relationship, Drug MeSH
- Animals MeSH
- Check Tag
- Rats MeSH
- Male MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Names of Substances
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine MeSH
- 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester MeSH
- Receptors, Adrenergic MeSH
- Calcium Channel Agonists MeSH
- fasudil MeSH Browser
- rho-Associated Kinases MeSH
- Nifedipine MeSH
- Norepinephrine MeSH
- Nitric Oxide MeSH
- rhoA GTP-Binding Protein MeSH
- Calcium MeSH
- Calcium Channels, L-Type 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.
References provided by Crossref.org
Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension
