Ontogenetic changes in contribution of calcium sensitization and calcium entry to blood pressure maintenance of Wistar-Kyoto and spontaneously hypertensive rats
Language English Country Netherlands Media print
Document type Journal Article, Research Support, Non-U.S. Gov't
- MeSH
- 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine analogs & derivatives pharmacology MeSH
- Arteries drug effects physiopathology MeSH
- Calcium Channel Blockers pharmacology MeSH
- Gene Expression drug effects MeSH
- Rho Guanine Nucleotide Exchange Factors genetics MeSH
- Phosphoproteins genetics metabolism MeSH
- Phosphorylation MeSH
- Hypertension physiopathology MeSH
- Protein Kinase Inhibitors pharmacology MeSH
- rho-Associated Kinases antagonists & inhibitors metabolism MeSH
- Blood Pressure drug effects physiology MeSH
- Rats MeSH
- RNA, Messenger metabolism MeSH
- Nifedipine pharmacology MeSH
- Rats, Inbred SHR MeSH
- Rats, Inbred WKY MeSH
- rhoA GTP-Binding Protein metabolism MeSH
- Signal Transduction MeSH
- Muscle Contraction MeSH
- Muscle Proteins genetics metabolism MeSH
- Muscle, Smooth, Vascular drug effects physiology MeSH
- Calcium metabolism MeSH
- Calcium Channels, L-Type drug effects metabolism MeSH
- Guanine Nucleotide Exchange Factors genetics 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
- Arhgef11 protein, rat MeSH Browser
- Arhgef12 protein, rat MeSH Browser
- Calcium Channel Blockers MeSH
- Rho Guanine Nucleotide Exchange Factors MeSH
- fasudil MeSH Browser
- Phosphoproteins MeSH
- Protein Kinase Inhibitors MeSH
- rho-Associated Kinases MeSH
- RNA, Messenger MeSH
- Nifedipine MeSH
- p63RhoGEF protein, rat MeSH Browser
- Ppp1r14a protein, rat MeSH Browser
- rhoA GTP-Binding Protein MeSH
- Muscle Proteins MeSH
- Calcium MeSH
- Calcium Channels, L-Type MeSH
- Guanine Nucleotide Exchange Factors MeSH
BACKGROUND: Altered calcium sensitization (mediated by RhoA/Rho-kinase pathway) and enhanced calcium entry through L-type voltage-dependent calcium channels (L-VDCCs) participate in blood pressure (BP) maintenance of adult spontaneously hypertensive rats (SHRs). This study aimed to evaluate ontogenetic changes of these two pathways in BP control of SHR and Wistar-Kyoto (WKY) aged 3, 5, 7, 13, 26 and 42 weeks. METHODS: BP response to acute administration of Rho-kinase inhibitor fasudil or L-VDCC blocker nifedipine and the expression of particular components of RhoA/Rho-kinase pathway were determined in young and adult animals. RESULTS: Fasudil-induced BP reduction was attenuated in young SHR compared with WKY, but was enhanced in adult SHR. In contrast, BP response to nifedipine was similar in 3-week-old SHR and WKY and it was augmented with age in SHR but not in WKY. Consequently, the ratio between fasudil-induced and nifedipine-induced BP changes was lower in all age groups of SHR compared with WKY. Fasudil effects on contractility of isolated arteries were attenuated in young but not in adult SHR. mRNA expression of selected Rho-GEFs (Arhgef1, Arhgef11 and Arhgef12) was decreased only in adult SHR, whereas p63RhoGEF and CPI-17 expression was reduced in both age groups of SHR. Active RhoA and phosphorylated CPI-17 were increased in adult but not in young SHR. CONCLUSION: The importance of RhoA/Rho-kinase pathway for BP/vascular tone control is attenuated in SHR from prehypertensive stages. Enhanced RhoA activation and/or CPI-17 phosphorylation might be counteracted by reduced expression of upstream activators of Rho-kinase (Rho-GEFs) together with lower expression of CPI-17 (in downstream cascade of Rho-kinase).
References provided by Crossref.org
Altered Balance between Vasoconstrictor and Vasodilator Systems in Experimental Hypertension
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