Abstract 521: Cardiovascular Phenotype in Mice with Renovascular Hypertension and Type II Diabetes
Background: Combined renovascular hypertension (RVH) and type II diabetes (DM II) are a major health problem. Both share common risk factors and contribute to cardiovascular morbidity and mortality. We recently observed a high mortality rate in DM II mice (dbdb) with RVH.
Purpose: We sought to determine the interactions between renovascular hypertension and DM II on the cardiovascular phenotype in dbdb mice with RVH.
Methods and Materials: RVH was established by placing a polytetrafluoroethylene cuff on the right renal artery of C57BL/KS (wild type, WT) or dbdb mice.
We divided the mice into four groups: WT sham, WT type RAS, dbdb sham, dbdb RAS. We examined the blood pressure, plasma angiotensin I, renin, heart weight and myocyte diameter. Histologic parameters including inflammation, necrosis and fibrosis were assessed semiquantitively.
Results: Blood pressure, Renin, Plasma angiotensin I: RAS produced a similar elevation in systolic blood pressure (SBP), renin mRNA expression, and plasma angiotensin I content in WT and dbdb mice with RAS.
Heart weight: Despite similar elevation in SBP, db/db RAS mice showed a greater increase in heart weight than WT RAS mice (163.7 +/- 6.4 mmHg vs 145.7 +/- 2.3; n=23).. Similar trends were observed on normalization of the heart weight to tibial length.
Cardiac myocyte diameter: Cardiac myocyte diameter in WT RAS (n=26) was significantly higher than in WT sham (n=15; 16.4 ± 0.3 vs. 15.0 ± 0.3 μm, p=0.0031). Myocyte diameter was higher in dbdb RAS mice (n=19, 14.76 ± 0.35) than dbdb sham (15.94 ± 0.29 μm, p= 0.0126). However, myocyte diameter was similar in dbdb RAS and WT RAS mice (16.4 ± 0.3 vs. 15.9 ± 0.3 μm, p=0.3).
Histology: Sham groups had no inflammation (INF) or necrosis (NEC). Interstitial fibrous tissue was increased in dbdb RAS mice (28% by area) vs WT RAS (19% by area). Dbdb RAS mice had more severe INF (severe in 18%, mild in 82%) than WT RAS (severe in 0%, jild in 12%). Severe NEC was found in 32.1% of dbdb compared to 11.5% of WT RAS.
Conclusion: The histologic changes and hypertrophy of the heart superimpose in dbdb RAS compared to WT RAS. This indicates that the risk of cardiovascular morbidity and mortality increases synergisticly in the presence of DM II and RVH.
Author Disclosures: Y. Al-Saiegh: None. B.E. Knudsen: None. S. Hartono: None. J.P. Grande: None.
- © 2014 by American Heart Association, Inc.