To investigate lisinopril effect on the contribution of nitric oxide (NO) and K(Ca) channels to acetylcholine (ACh)-induced relaxation in isolated mesenteric arteries of spontaneously hypertensive rats (SHRs). Third branch mesenteric arteries isolated from lisinopril treated SHR rats (20 mg/kg/day for ten weeks, SHR-T) or untreated (SHR-UT) or normotensive WKY rats were mounted on tension myograph and ACh concentration-response curves were obtained. Westernblotting of eNOS and K(Ca) channels was performed. ACh-induced relaxations were similar in all groups while L-NMMA and indomethacin caused significant rightward shift only in SHR-T group. Apamin and TRAM-34 (SK(Ca) and IK(Ca) channels blockers, respectively) significantly attenuated ACh-induced maximal relaxation by similar magnitude in vessels from all three groups. In the presence of L-NMMA, indomethacin, apamin and TRAM-34 further attenuated ACh-induced relaxation only in SHR-T. Furthermore, lisinopril treatment increased expression of eNOS, SK(Ca) and BK(Ca) proteins. Lisinopril treatment increased expression of eNOS, SK(Ca), BK(Ca) channel proteins and increased the contribution of NO to ACh-mediated relaxation. This increased role of NO was apparent only when EDHF component was blocked by inhibiting SK(Ca) and IK(Ca) channels. Such may suggest that in mesenteric arteries, non-EDHF component functions act as a reserve system to provide compensatory vasodilatation if (and when) hyperpolarization that is mediated by SK(Ca) and IK(Ca) channels is reduced.
- MeSH
- antihypertenziva farmakologie MeSH
- arteriae mesentericae účinky léků metabolismus patofyziologie MeSH
- blokátory draslíkových kanálů farmakologie MeSH
- draslíkové kanály aktivované vápníkem účinky léků metabolismus MeSH
- hypertenze farmakoterapie metabolismus patofyziologie MeSH
- inhibitory ACE farmakologie MeSH
- lisinopril farmakologie MeSH
- modely nemocí na zvířatech MeSH
- nízkovodivostní draslíkové kanály aktivované vápníkem účinky léků metabolismus MeSH
- oxid dusnatý metabolismus MeSH
- potkani inbrední SHR MeSH
- potkani inbrední WKY MeSH
- signální transdukce účinky léků MeSH
- synthasa oxidu dusnatého, typ III antagonisté a inhibitory metabolismus MeSH
- vápníkem aktivované draslíkové kanály s vysokou vodivostí - alfa-podjednotky účinky léků metabolismus MeSH
- vápníkem aktivované draslíkové kanály se střední vodivostí účinky léků metabolismus MeSH
- vazodilatace účinky léků MeSH
- vazodilatancia farmakologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
