Pharmacological potentiation of the efferent vagus nerve attenuates blood pressure and renal injury in a murine model of systemic lupus erythematosus

Grace S. Pham, Lei A. Wang, Keisa W. Mathis

Research output: Contribution to journalArticle

8 Scopus citations

Abstract

Recent evidence suggests hypertension may be secondary to chronic inflammation that results from hypoactive neuro-immune regulatory mechanisms. To further understand this association, we used systemic lupus erythematosus (SLE) as a model of inflammation-induced hypertension. In addition to prevalent inflammatory kidney disease and hypertension, SLE patients suffer from dysautonomia in the form of decreased efferent vagal tone. Based on this, the cholinergic anti-inflammatory pathway, an endogenous vagus-to-spleen mechanism that, when activated results in decreases in systemic inflammation, may be compromised in SLE. We hypothesized that stimulation of the cholinergic anti-inflammatory pathway via pharmacological potentiation of the efferent vagus nerve would reduce inflammation and halt the development of hypertension and renal injury in SLE. Female NZBWF1 mice, an established model of murine SLE, and female control mice were treated with galantamine (4 mg/kg daily ip), an acetylcholinesterase inhibitor, or saline for 14 days. At the end of therapy, carotid catheters were surgically implanted and were used to measure mean arterial pressure before the animals were euthanized. Chronic galantamine administration attenuated both splenic and renal cortical inflammation, which likely explains why the hypertension and renal injury (i.e., glomerulosclerosis and fibrosis) typically observed in murine SLE was attenuated following therapy. Based on this, the anti-inflammatory, antihypertensive, and renoprotective effects of galantamine may be mediated through activation of the cholinergic anti-inflammatory pathway. It is possible that dysfunction of the cholinergic anti-inflammatory pathway exists in SLE at the level of the efferent vagus nerve and promoting restoration of its activity through central cholinergic receptor activation may be beneficial.

Original languageEnglish
Pages (from-to)R1261-R1271
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Volume315
Issue number6
DOIs
StatePublished - Dec 2018

Keywords

  • Galantamine
  • Hypertension
  • Lupus nephritis
  • Neuroimmune
  • Renal inflammation

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