Relaxin increases sympathetic nerve activity and activates spinally projecting neurons in the paraventricular nucleus of nonpregnant, but not pregnant, rats

Am J Physiol Regul Integr Comp Physiol. 2015 Dec 15;309(12):R1553-68. doi: 10.1152/ajpregu.00186.2015. Epub 2015 Sep 23.


Pregnancy is characterized by increased blood volume and baseline sympathetic nerve activity (SNA), vasodilation, and tachycardia. Relaxin (RLX), an ovarian hormone elevated in pregnancy, activates forebrain sites involved in control of blood volume and SNA through ANG II-dependent mechanisms and contributes to adaptations during pregnancy. In anesthetized, arterial baroreceptor-denervated nonpregnant (NP) rats, RLX microinjected into the subfornical organ (SFO; 0.77 pmol in 50 nl) produced sustained increases in lumbar SNA (8 ± 3%) and mean arterial pressure (MAP; 26 ± 4 mmHg). Low-dose intracarotid artery infusion of RLX (155 pmol·ml(-1)·h(-1); 1.5 h) had minor transient effects on AP and activated neurons [increased Fos-immunoreactivity (IR)] in the SFO and in spinally projecting (19 ± 2%) and arginine-vasopressin (AVP)-IR (21 ± 5%) cells in the paraventricular nucleus of the hypothalamus of NP, but not pregnant (P), rats. However, mRNA for RLX and ANG II type 1a receptors in the SFO was preserved in pregnancy. RLX receptor-IR is present in the region of the SFO in NP and P rats and is localized in astrocytes, the major source of angiotensinogen in the SFO. These data provide an anatomical substrate for a role of RLX in the resetting of AVP secretion and increased baseline SNA in pregnancy. Since RLX and ANG II receptor expression was preserved in the SFO of P rats, we speculate that the lack of response to exogenous RLX may be due to maximal activation by elevated endogenous levels of RLX in near-term pregnancy.

Keywords: ANG II; Fos; arginine-vasopressin; circumventricular organs; paraventricular nucleus; subfornical organ.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Arginine Vasopressin / metabolism
  • Arterial Pressure
  • Biomarkers / metabolism
  • Female
  • Infusions, Intra-Arterial
  • Microinjections
  • Neuroanatomical Tract-Tracing Techniques
  • Paraventricular Hypothalamic Nucleus / drug effects
  • Paraventricular Hypothalamic Nucleus / metabolism*
  • Pregnancy
  • Proto-Oncogene Proteins c-fos / metabolism
  • RNA, Messenger / metabolism
  • Rats, Sprague-Dawley
  • Receptor, Angiotensin, Type 1 / genetics
  • Receptor, Angiotensin, Type 1 / metabolism
  • Receptors, G-Protein-Coupled / agonists
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / metabolism
  • Receptors, Peptide / agonists
  • Receptors, Peptide / genetics
  • Receptors, Peptide / metabolism
  • Relaxin / administration & dosage
  • Relaxin / metabolism*
  • Signal Transduction / drug effects
  • Spinal Nerves / drug effects
  • Spinal Nerves / metabolism*
  • Subfornical Organ / drug effects
  • Subfornical Organ / metabolism*
  • Sympathetic Nervous System / drug effects
  • Sympathetic Nervous System / metabolism*
  • Time Factors


  • Agtr1a protein, rat
  • Biomarkers
  • Proto-Oncogene Proteins c-fos
  • RNA, Messenger
  • Receptor, Angiotensin, Type 1
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • relaxin receptors
  • Arginine Vasopressin
  • Relaxin