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Timing of Blood Pressure Rhythms Predict Risk of Renal Injury in the Dahl Salt‐Sensitive Rats
Author(s) -
Chen Daian,
Booth John N.,
Houchin Colton,
Colson Jackson C.,
Jin Chunhua,
Cowley Allen W.,
Geurts Aron,
Muntner Paul,
Young Martin E.,
Pollock David M.,
Pollock Jennifer S.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.905.11
Subject(s) - blood pressure , medicine , circadian rhythm , endocrinology , introgression , biology , gene , biochemistry
Salt‐sensitive individuals have higher susceptibility for dysfunctional diurnal blood pressure rhythms, development of hypertension and renal injury. The aim of this study was to elucidate genetic determinants of diurnal excretion of renal injury markers and timing of systolic BP (SBP) peak and trough patterns in 4 rat models of salt‐sensitivity. We utilized male Dahl salt‐sensitive (SS) rats, NADPH oxidase p67phox knockout in SS (SS.p67phox −/− ), introgression of chromosome 13 from Brown‐Norway rats into SS (SS.BN13), and introgression of 16Mbp section of BN13 (SS.BN‐(D13Rat151‐D13Rat197)) in SS (SS.Line26). Male, 12–14 week old rats (n=7–14) were maintained on normal salt (NS; 0.4% NaCl) and then fed high salt (HS; 4% NaCl) diet for 7 days (Dyets, AIN‐76A). Telemetry was used to continuously measure SBP, heart rate and locomotor activity. On NS, 24‐hr SBP was 155.9 ± 0.2 mmHg (SS), 141.6 ± 0.3 mmHg (SSp67phox −/− ), 145.5 ± 0.4 mmHg (SS.BN13), and 155.2 ± 0.2 mmHg (SS.Line26). The average 24‐hr SBP in rats on high salt diet was 173.3 ± 0.5 mmHg, 152.2 ± 0.5 mmHg, 158.5 ± 0.6 mmHg, and 171.0 ± 0.6 mmHg, respectively. Eating HS did not change the timing of peak and trough SBP rhythms within each genotype. Furthermore, there were no differences in timing of peak timing of SBP across genotypes on either diet. Similarly, there was no difference in timing of trough SBP across genotypes on NS. However, HS delayed the timing of trough SBP in SS (n=14) by 5.3 hours compared to SS.p67phox −/− (n=12, p<0.001) and by 2.6 hours compared to SS.BN13 rats (n=7, p=0.036). Timing of trough SBP was similar between SS.Line26 (n=12) and SS rats. Heart rate and locomotor activity were not significantly different across genotypes or diets. On HS diet, SS.p67phox −/− (n=8) had lower proteinuria and albuminuria than SS (n=14) and SS.Line26 (n=12) during the active phase (p<0.0001). On HS, proteinuria, albuminuria, and nephrinuria were highest in SS.Line26 compared to SS, SS.p67phox −/− , and SS.BN13 (n=7) during active phase (p<0.01). Excretion of kidney injury marker 1, KIM1, was significantly higher in SS than SS.Line26, SS.BN13, and SS.p67phox −/− (p<0.005). In summary, SS and SS.Line26 rats have delays in the inactive (trough) timing of SBP, which is associated with proximal tubular injury in SS and glomerular injury in SS.Line26 rats. These findings indicate that rat chromosome 13 has a role at least in part, in the timing of SBP and risk of kidney injury in the SS rat. Support or Funding Information American Heart Association Strategically Focused Research Network ‐ Hypertension (15SFRN2390002) This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .