Faculty Collaboration Database

The complement system in hypertension and renal damage in the Dahl SS rat. Physiol Rep 2018 Mar;6(6):e13655

Date

03/30/2018

Pubmed ID

29595916

Pubmed Central ID

PMC5875537

DOI

10.14814/phy2.13655

Scopus ID

2-s2.0-85044747816 (requires institutional sign-in at Scopus site)   16 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.

Author List

Regal JF, Laule CF, McCutcheon L, Root KM, Lund H, Hashmat S, Mattson DL

MESH terms used to index this publication - Major topics in bold

Animals
Complement System Proteins
Hypertension
Kidney Diseases
Male
Rats
Rats, Inbred Dahl
Sodium Chloride, Dietary