The effects of LXR agonist GW3965 on vascular reactivity and inflammation in hypertensive rat aorta

Life Sci. 2018 Nov 15;213:287-293. doi: 10.1016/j.lfs.2018.10.042. Epub 2018 Oct 23.

Abstract

Aims: Liver X receptors (LXRs) play an important role in the regulation of cholesterol, fatty acid and glucose metabolisms together with inflammatory processes. In the present study, the effects of LXR agonist GW3965 on vascular reactivity and expression of functional proteins in DOCA-Salt induced hypertension were examined.

Main methods: Hypertension was induced through unilateral nephrectomy and deoxycorticosterone-acetate (DOCA) injection (20 mg/kg, twice a week) for 6 weeks in male Wistar albino rats (8 weeks old). An LXR agonist GW3965 (10 mg/kg/day, i.p.) was administered to animals for last seven days.

Key findings: GW3965 treatment reduced systolic blood pressures in hypertensive rats. Acetylcholine-induced endothelium-dependent and sodium nitroprusside-induced endothelium-independent vasorelaxations were decreased in hypertensive rats but not affected by GW3965. GW3965 treatment enhanced plasma nitrite levels in normotensive rats. KCl and phenylephrine (Phe)-induced vasocontractions were reduced in hypertensive groups and increased with GW3965 treatment. Decreased sarco/endoplasmic reticulum Ca2+-ATPase2 (SERCA2) expression in the hypertensive aorta was not changed by GW3965 treatment. Expression of inositoltrisphosphate receptor1 (IP3R1) was increased by GW3965 in normotensive animals. The nuclear factor kappaB (NF-κB) and tumor necrosis factor alpha (TNF-α) expressions were increased in hypertensive rats and reduced by GW3965 treatment.

Significance: The results of study indicate that the LXR agonist, GW3965, exhibited a beneficial effect on increased blood pressure and improved hypertension-induced impairment in contractile activity of vessel and inflammatory markers in vascular tissue. Therefore, these effects of LXR agonists on vessel should be taken into account in experimental or therapeutic approaches to hypertension.

Keywords: Aorta; GW3965; Hypertension; Inflammation; Liver X receptors.

MeSH terms

  • Animals
  • Aorta / drug effects
  • Benzoates / metabolism
  • Benzoates / pharmacology*
  • Benzylamines / metabolism
  • Benzylamines / pharmacology*
  • Blood Pressure / drug effects
  • Cardiovascular Diseases
  • Desoxycorticosterone Acetate / pharmacology
  • Disease Models, Animal
  • Hypertension / drug therapy*
  • Hypertension / physiopathology
  • Inflammation / drug therapy
  • Inflammation / physiopathology
  • Liver X Receptors / agonists
  • Liver X Receptors / metabolism
  • Male
  • Nitroprusside / pharmacology
  • Rats
  • Rats, Wistar

Substances

  • Benzoates
  • Benzylamines
  • GW 3965
  • Liver X Receptors
  • Nitroprusside
  • Desoxycorticosterone Acetate