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  • Meeting abstract
  • Open Access

Natriuretic peptides regulate sympathetic nervous activity independent of mineralocorticoid receptor

BMC Pharmacology and Toxicology201516 (Suppl 1) :A71

  • Published:


  • Sympathetic Nervous System
  • Mineralocorticoid Receptor
  • Eplerenone
  • Sympathetic Nervous System Activity
  • Sodium Load


Natriuretic peptides (ANP/BNP) increase cGMP and exert cardiovascular protective effects via guanylyl cyclase A (GC-A) receptor, which is distributed in many organs such as the heart, the vasculature and the brain [1]. Sympathetic nervous system (SNS) as well as renin-angiotensin-aldosterone-system contributes to cardiovascular disease. However, the endogenous effect of GC-A signaling on SNS is not investigated. Recent study shows that activated mineralocorticoid receptor (MR) in the hypothalamus induces systemic SNS activation [2], whereas ANP infusion in human inhibited SNS activity in the heart [3]. Notably, it is reported that ANP counteracts the deleterious effects of MR in the heart [4]. Therefore, we hypothesized that ANP suppresses MR activation in the brain and leads to the inhibition of SNS activity.


To investigate whether ANP/GC-A signaling inhibits SNS activity through the suppression of the brain MR, we examined urinary catecholamine secretion in global GC-A receptor KO mice and the effect of intracerebroventricular (ICV) infusion of MR blocker.

Methods and results

We measured blood pressure (BP) and urinary norepinephrine (U-NE) secretion in wild type and global GC-A KO mice. Both BP and U-NE is significantly higher in GC-A KO than in wild type mice, indicating SNS is activated in GC-A KO mice. To study whether SNS activation is caused by the brain MR, we infused Eplerenone (MR blocker) into the ICV with osmotic mini pump for 2 weeks. Contrary to our hypothesis, both BP and U-NE did not change after 2 weeks ICV infusion, suggesting that activated SNS in GC-A KO is independent of MR. Furthermore, high sodium diet (NaCl 6%) for 2 weeks did not increase BP and U-NE in GC-A KO mice. MR protein expression in the hypothalamus was almost similar between GC-A KO and Wild type mice. These data suggest that SNS activity in GC-A KO mice is independent of MR and insensitive to sodium load. Unexpectedly, the most of GC-A KO mice died after ICV infusion of Losartan (AT1 receptor blocker), whereas wild type mice survived.


Natriuretic peptides/GC-A signaling regulates SNS activity independent of both brain MR and sodium load. Brain AT1 receptor might be important in the regulation of cardiovascular system in global GC-A KO mice.

Authors’ Affiliations

First Department of Internal Medicine, Nara Medical University, Kashihara, Japan


  1. Kuhn M: Structure, regulation, and function of mammalian membrane guanylyl cyclase receptors, with a focus on guanylyl cyclase-A. Circ Res. 2003, 93 (8): 700-709. 10.1161/01.RES.0000094745.28948.4D.View ArticlePubMedGoogle Scholar
  2. Hamlyn JM, Blaustein MP: Salt sensitivity, endogenous ouabain and hypertension. Curr Opin Nephrol Hypertens. 2013, 22 (1): 51-58.PubMedPubMed CentralGoogle Scholar
  3. Kasama S, Toyama T, Kumakura H, Takayama Y, Ishikawa T, Ichikawa S, et al: Effects of intravenous atrial natriuretic peptide on cardiac sympathetic nerve activity in patients with decompensated congestive heart failure. J Nucl Med. 2004, 45 (7): 1108-1113.PubMedGoogle Scholar
  4. Nakagawa H, Oberwinkler H, Nikolaev VO, Gaßner B, Umbenhauer S, Wagner H, et al: Atrial natriuretic peptide locally counteracts the deleterious effects of cardiomyocyte mineralocorticoid receptor activation. Circ Heart Fail. 2014, 7 (5): 814-821. 10.1161/CIRCHEARTFAILURE.113.000885.View ArticlePubMedGoogle Scholar


© Nakagawa et al. 2015

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