Combined treatment with epoxyeicosatrienoic acid analog and 20-hydroxyeicosatetraenoic acid antagonist provides substantial hypotensive effect in spontaneously hypertensive rats
Jazyk angličtina Země Nizozemsko Médium print
Typ dokumentu časopisecké články, práce podpořená grantem
- MeSH
- antihypertenziva farmakologie MeSH
- hypertenze metabolismus MeSH
- ikosanoidy farmakologie MeSH
- krevní tlak účinky léků MeSH
- krysa rodu Rattus MeSH
- kyseliny hydroxyeikosatetraenové antagonisté a inhibitory MeSH
- potkani inbrední SHR 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
- 20-hydroxy-5,8,11,14-eicosatetraenoic acid MeSH Prohlížeč
- antihypertenziva MeSH
- ikosanoidy MeSH
- kyseliny hydroxyeikosatetraenové MeSH
OBJECTIVES: The global morbidity and mortality related to hypertension and associated disorders increases continuously and novel therapeutic strategies are still in high demand. Increasing evidence suggests the important role in blood pressure regulation of cytochrome P-450-dependent metabolites of arachidonic acid. Epoxyeicosatrienoic acids (EETs) induce vasodilation and natriuresis, and have renoprotective and anti-inflammatory properties. 20-HETE is an arachidonic acid metabolite with both prohypertensive and antihypertensive activities. To explore the pathophysiological role of arachidonic acid metabolites in more detail, we examined the antihypertensive efficiency of EET-A, a stable analog of 14,15-EET, and of AAA, a novel antagonist of the 20-HETE receptors. METHODS: Male spontaneously hypertensive rats (SHR) were treated for 5 weeks with EET-A, AAA or the combination; age-matched untreated SHR and normotensive Wistar-Kyoto rats served as controls. EET-A and AAA were administered in drinking water at 10 mg/kg/day each. SBP was measured by telemetry and urine, blood, and tissue samples were collected for relevant analyses. RESULTS: EET-A or AAA given alone had no significant effect on SHR blood pressure. In contrast, combined treatment with AAA and EET-A was significantly antihypertensive, causing a decrease in SBP from 180 ± 3 to 160 ± 5 mmHg (P < 0.05). Additionally, the combined treatment attenuated cardiac hypertrophy, decreased kidney ANG II level, increased natriuresis, and increased the excretion of nitric oxide metabolites. CONCLUSION: Considering the beneficial impact of the combined treatment with EET-A and AAA on SHR blood pressure and cardiovascular and renal function, we suggest that the treatment is a promising therapeutic strategy for human hypertension.
Center for Experimental Medicine Institute for Clinical and Experimental Medicine
Department of Biochemistry University of Texas Southwestern Medical Center Dallas Texas
Department of Pathophysiology 2nd Faculty of Medicine Charles University Prague Czech Republic
Department of Pharmacology and Toxicology Medical College of Wisconsin Wisconsin USA
Citace poskytuje Crossref.org
