The endothelium contributes to the maintenance of vasodilator tone by releasing endothelium-derived relaxing factors, including nitric oxide (NO). In hypertension, endothelial nitric oxide synthase (eNOS) produces less NO and could be one of the contributing factors to the increased peripheral vascular resistance. Agonist-induced Ca(2+) entry is essential for the activation of eNOS. The transient receptor potential vanilloid type 4 (TRPV4) channel, a Ca(2+)-permeant cation channel, is expressed in the endothelial cells and involved in the regulation of vascular tone. The present study aimed to investigate the role of TRPV4 channel in endothelium-dependent NO-mediated relaxation of the resistance artery in hypertensive rats. Using a wire myograph, relaxation response to the TRPV4 activator, 4alpha-phorbol-12,13-didecanoate (4alphaPDD) was assessed in mesenteric arteries obtained from Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHRs). Compared to WKY, SHR demonstrated a significantly attenuated 4alphaPDD-induced endothelium-dependent NO-mediated relaxation. Immunohistochemical analysis revealed positive staining for TRPV4 in the endothelium of mesenteric artery sections in both WKY and SHR. Furthermore, TRPV4 mRNA and protein expressions in SHR were significantly lower than their expression levels in WKY rats. We conclude that 4alphaPDD-induced endothelium-dependent NO-mediated vasorelaxation is reduced in SHR and downregulation of TRPV4 could be one of the contributing mechanisms.

• MeSH
• arteriae mesentericae účinky léků   metabolismus   patofyziologie   MeSH
• cévní endotel účinky léků   metabolismus   MeSH
• down regulace účinky léků   fyziologie   MeSH
• forboly farmakologie   MeSH
• hypertenze metabolismus   patofyziologie   MeSH
• kationtové kanály TRPV agonisté   metabolismus   MeSH
• krysa rodu rattus MeSH
• orgánové kultury - kultivační techniky MeSH
• potkani inbrední SHR MeSH
• potkani inbrední WKY MeSH
• synthasa oxidu dusnatého, typ III metabolismus   MeSH
• vazodilatace účinky léků   fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

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

The aim of this work was to investigate the effect of 10 weeks of lisinopril treatment to spontaneously hypertensive rats (SHRs) on day/night variations of blood pressure, heart rate and autonomic cardio-regulation parameters. Male SHR with surgically implanted radio-telemetry implant that provided direct measurements of arterial pressure and electrocardiogram wave were used. Animals were allocated to two groups (n=5 each). The first group was treated with lisinopril (20 mg/kg by gavage) daily for 10 weeks (treated group); whereas the second was gavaged daily with tap water (untreated group). Arterial blood pressure, ECG and other telemetry parameters were recorded at the start and at the end of 10-week treatment. Collected data were analyzed using specialized software and were statistically tested. In addition to the expected lowering of blood pressure, spectral analysis of R-R intervals revealed that lisinopril treatment for 10 weeks significantly caused 2-3 fold increase in heart rate variability (HRV) during both active and inactive periods. However, R-R interval durations demonstrated variable distribution patterns during those periods. The cause of observed distribution pattern of R-R intervals during active and inactive periods may be of significance to better understand HRV changes and warrants further investigations.

• MeSH
• antihypertenziva aplikace a dávkování   MeSH
• autonomní nervový systém účinky léků   patofyziologie   MeSH
• cirkadiánní rytmus účinky léků   MeSH
• hypertenze farmakoterapie   patofyziologie   MeSH
• krevní tlak účinky léků   MeSH
• krysa rodu rattus MeSH
• lisinopril MeSH
• potkani inbrední SHR MeSH
• srdeční frekvence účinky léků   MeSH
• výsledek terapie MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH