Novel mechanism of brain soluble epoxide hydrolase‐mediated blood pressure regulation in the spontaneously hypertensive rat

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Abstract
SPECIFIC AIMSGene profiling using microarray technology revealed that soluble epoxide hydrolase (sEH) mRNA levels were elevated in the spontaneously hypertensive rat (SHR) vs. the Wistar Kyoto (WKY) rat brain. Peripheral sEH overexpression has been linked to animal models of hypertension, and inhibition of sEH activity by pharmacological agents decreased high blood pressure (BP). Whereas sEH in the vasculature is proposed to exert its actions by converting vasodilatory epoxyeicosatrienoic acids (EETs) to their relatively inactive diol forms, the role of this enzyme in the brain is unknown. Thus, our objective was to investigate the involvement of brain sEH in BP control.PRINCIPAL FINDINGS1. sEH is up-regulated in the hypothalamus and brainstem of the SHROur first objective was to validate sEH expression changes identified in microarray analysis. Real-time RT-PCR and Western blot analysis revealed that sEH expression was several fold higher in the brainstem and hypothalamus of adult SHR than in WKY rats. T...
Funding Information
  • National Institutes of Health (HL33610, HL56921 (MKR), R37 ES02710, P30 ES05707, P42 ES04699 (BDH & CM), GM31278)
  • Welch Foundation
  • British Heart Foundation