The complement system in hypertension and renal damage in the Dahl SS rat

Jean F. Regal, Connor F. Laule, Luke McCutcheon, Kate M. Root, Hayley Lund, Shireen Hashmat, David L. Mattson

Research output: Contribution to journalArticle

5 Scopus citations

Abstract

Evidence indicates the immune system is important in development of hypertension and kidney disease. In the Dahl Salt-Sensitive (SS) rat model, lymphocytes play a role in development of hypertension and kidney damage after increased sodium intake. Recent transcriptomic analyses demonstrate upregulation of the innate immune complement system in the kidney of Dahl SS rat fed a high-salt diet, leading us to hypothesize that inhibition of complement activation would attenuate development of hypertension and kidney damage. Male Dahl SS rats on a low salt (0.4% NaCl) diet were instrumented with telemeters for continuous monitoring of arterial blood pressure. Animals received saline vehicle (Control) or sCR1, a soluble form of endogenous Complement Receptor 1 (CR1; CD35) that inhibits complement activation. At Day 0, rats were switched to high salt (4.0% NaCl) diet and assigned to sCR1 (15 mg/kg per day) or Control groups with daily ip injections either days 1–7 or days 14–18. Urine was collected overnight for determination of albumin excretion. Treatment with sCR1, either immediately after high-salt diet was initiated, or at days 14–18, did not alter development of hypertension or albuminuria. The sCR1 dose effectively inhibited total hemolytic complement activity as well as C3a generation. High salt caused an increase in message for complement regulator Cd59, with minimal change in Crry that controls the C3 convertase. Thus, innate immune complement activation in the circulation is not critical for development of hypertension and kidney damage due to increased sodium intake, and therapeutic manipulation of the complement system is not indicated in salt-sensitive hypertension.

Original languageEnglish (US)
Article numbere13655
JournalPhysiological reports
Volume6
Issue number6
DOIs
StatePublished - Mar 2018
Externally publishedYes

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Keywords

  • C3a
  • complement
  • kidney
  • salt-sensitive hypertension

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)

Cite this

Regal, J. F., Laule, C. F., McCutcheon, L., Root, K. M., Lund, H., Hashmat, S., & Mattson, D. L. (2018). The complement system in hypertension and renal damage in the Dahl SS rat. Physiological reports, 6(6), [e13655]. https://doi.org/10.14814/phy2.13655