Possible role for brain prostanoid pathways in the development of angiotensin II-salt hypertension in rats

Ninitha Asirvatham-Jeyaraj, Gregory D. Fink

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3 Scopus citations

Abstract

Prostanoids generated by the cyclooxygenase (COX) pathway appear to contribute to the neurogenic hypertension (HTN) in rats. The first goal of this study was to establish the time frame during which prostanoids participate in ANG II-salt HTN. We induced HTN using ANG II (150 ng·kg−1·min−1 sc) infusion for 14 days in rats on a high-salt (2% NaCl) diet. When ketoprofen pretreatment was combined with treatment during the first 7 days of ANG II infusion, development of HTN and increased neurogenic pressor activity (indexed by the depressor response to ganglion blockade) were significantly attenuated for the entire ANG II infusion period. This suggests that prostanoid generation caused by administration of ANG II and salt leads to an increase in neurogenic pressor activity and blood pressure (BP) via a mechanism that persists without the need for continuing prostanoid input. The second goal of this study was to determine whether prostanoid products specifically in the brain contribute to HTN development. Expression of prostanoid pathway genes was measured in brain regions known to affect neurogenic BP regulation. ANG II-treated rats exhibited changes in gene expression of phospholipase A2 (upregulated in organum vasculosum of the lamina terminalis, paraventricular nucleus, nucleus of the solitary tract, and middle cerebral artery) and lipocalin-type prostaglandin D synthase (upregulated in the organum vasculosum of the lamina terminalis). On the basis of our results, we propose that activation of the brain prostanoid synthesis pathway both upstream and downstream from COX at early stages plays an important role in the development of the neurogenic component of ANG II-salt HTN.

Original languageEnglish (US)
Pages (from-to)R232-R242
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume311
Issue number2
DOIs
StatePublished - Aug 2016

Bibliographical note

Funding Information:
National Heart, Lung, and Blood Institute Grants RO1-HL-076312 and RCO-HL-060363 supported this research.

Keywords

  • Angiotensin II
  • Hypertension
  • Prostanoids
  • Salt
  • Sympathetic

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