Brown Norway chromosome 16 provides protection from cardiac fibrosis with pressure overloading on a Salt‐Sensitive Dahl background

Abstract

Myocardial fibrosis accumulates with age and often accompanies hypertension induced left ventricle (LV) hypertrophy. Previously we have shown that the normotensive SSBN16 consomic rat (Brown Norway (BN) chromosome 16 in Dahl Salt‐Sensitive (SS) rat genetic background) is better protected from developing LV fibrosis with aging than either the hypertensive SS or normotensive BN. We then hypothesized that the SSBN16 would also be better protected from developing fibrosis with an elevated afterload than the normotensive BN or SSBN13 consomic strains. To test this, 9 week old rats from each strain were subjected to 2 weeks of abdominal aortic occlusion (AAO) or sham operation (SOC). The AAO SSBN13 and BN rats achieved significantly elevated systolic blood pressures (SBP) (162±23 mmHg and 168±24 mmHg, respectively), while the SSBN16 SBP averaged only 141±5 mmHg. Examination of SSBN16 vasculature revealed that collateral blood vessels bypassed the occlusion in the AAO, but not SOC rats. The one‐kidney, one‐clip model was then applied to the SSBN16 producing an average SBP of 163±7 mmHg. With similarly elevated blood pressures the % of LV fibrosis was significantly increased in the SSBN13 and BN rats compared to SOC's, but not in the SSBN16 rats. These results suggest that genes on chromosome 16 protect against cardiac fibrosis associated with pressure overload hypertrophy. Supported by HL‐ U01 HL66579 and HL‐N01‐HV‐28182