The intermediary role of the central cyclooxygenase / lipoxygenase enzymes in intracerebroventricular injected nesfatin-1-evoked cardiovascular effects in rats

Neurosci Lett. 2021 Jun 21:756:135961. doi: 10.1016/j.neulet.2021.135961. Epub 2021 May 19.

Abstract

That nesfatin-1 is a neuromodulatory peptide for the cardiovascular system is well documented. Several central receptors have been shown to mediate the cardiovascular effects of nesfatin-1. Immunohistochemistry and Western blot studies showed that nesfatin-1 activated the expression of the central cyclooxygenase (COX) -1, -2 and lipoxygenase (LOX). In addition, microdialysis study showed that nesfatin-1 increased the release of total prostaglandins and leukotrienes from the hypothalamus. The present study investigated whether the central COX and LOX enzymes have a direct mediating role in the MAP and HR responses of nesfatin-1. Intracerebroventricularly administered nesfatin-1 produced dose-dependent pressor and phasic HR responses in normotensive conscious rats Sprague Dawley. Central pretreatment with a COX1/2 inhibitor, ibuprofen, completely blocked the nesfatin-1-induced responses. However, central pretreatment with a nonselective LOX inhibitor, nordihydroguaiaretic acid, partially attenuated the cardiovascular responses induced by nesfatin-1. The results suggest that centrally administered nesfatin-1 activates the central enzymes COX and LOX, which may be involved in the cardiovascular responses as a novel central mechanism for nesfatin-1.

Keywords: Cyclooxygenase; Heart rate; Intracerebroventricular; Lipoxygenase; Mean arterial blood pressure; Nesfatin-1.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arterial Pressure / drug effects*
  • Cardiovascular System / drug effects
  • Cyclooxygenase 2 Inhibitors / pharmacology
  • Dose-Response Relationship, Drug
  • Heart Rate / drug effects*
  • Hypothalamus / drug effects*
  • Hypothalamus / metabolism
  • Ibuprofen / pharmacology
  • Lipoxygenase / metabolism*
  • Male
  • Nucleobindins / administration & dosage*
  • Prostaglandin-Endoperoxide Synthases / metabolism*
  • Rats
  • Rats, Sprague-Dawley

Substances

  • Cyclooxygenase 2 Inhibitors
  • Nucb2 protein, rat
  • Nucleobindins
  • Lipoxygenase
  • Prostaglandin-Endoperoxide Synthases
  • Ibuprofen