Central angiotensinergic mechanisms in female spontaneously hypertensive rats treated with estradiol

Appetite. 2022 Jul 1:174:106012. doi: 10.1016/j.appet.2022.106012. Epub 2022 Mar 31.

Abstract

Estrogens reduce 0.3 M NaCl intake and palatability in a widely used model of essential hypertension, the spontaneously hypertensive rats (SHRs). Here we investigated whether the inhibitory effects of β-estradiol (E2, 10 μg/kg b.w. subcutaneously for 8 days) on water deprived partially-rehydrated (WD-PR) ovariectomized (OVX) adult female SHRs (fSHRs, n = 4-10/group) are related to interferences on brain angiotensin II AT1 receptors (AT1r). After WD-PR, E2 reduced 0.3 M NaCl intake (1.3 ± 0.6, vs. vehicle: 3.5 ± 1.2 ml/30 min), the number of hedonic responses to intraoral NaCl infusion (57 ± 11, vs. vehicle: 176 ± 32/min), and the relative angiotensin AT1r (Agtr1a) mRNA expression in the hypothalamus. Losartan (AT1r antagonist, 100 μg) intracerebroventricularly in OVX fSHRs treated with vehicle subcutaneously abolished 0.3 M NaCl intake (0.1 ± 0.1 ml/30 min) and only transiently reduced hedonic responses to intraoral NaCl. Losartan combined with E2 decreased the number of hedonic and increased the number of aversive responses to intraoral NaCl and abolished 0.3 M NaCl intake. E2 also reduced the pressor and dipsogenic responses to intracerebroventricular angiotensin II. The results suggest that AT1r activation increases palatability and induces NaCl intake in WD-PR fSHRs. E2 reduced hypothalamic Agtr1a mRNA expression, which may account for the effects of E2 on NaCl intake and palatability and intracerebroventricular angiotensin II-induced pressor and dipsogenic responses in OVX fSHRs. Future studies considering natural fluctuations in estrogen secretion might help to determine the degree of such interference in brain neuronal activity.

Keywords: Dehydration; Estrogens; Hypertension; Palatability; Sodium.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Angiotensin II* / pharmacology
  • Animals
  • Estradiol / pharmacology
  • Female
  • Humans
  • Losartan* / pharmacology
  • RNA, Messenger
  • Rats
  • Rats, Inbred SHR
  • Receptor, Angiotensin, Type 1 / genetics
  • Sodium Chloride

Substances

  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Angiotensin II
  • Sodium Chloride
  • Estradiol
  • Losartan