Abstract 528: Angiotensin-ii Induces Strain-dependent Renovascular Remodeling in Mice
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Abstract
Activation of renin-angiotensin system and production of Angiotensin-II plays an important role in several pathological processes leading to end stage renal disease. Sustained hypertension induces renovascular remodeling in both intra and extra-renal vasculature by altering extracellular matrix (ECM) components. Recent studies in vascular remodeling have shown strain-dependent phenotypic variation in carotid artery and in pulmonary hypertension indicating a genetic basis for disease susceptibility. We hypothesized that sensitivity to develop hypertension to angiotensin-II infusion and subsequent renovascular remodeling will vary depending on the genetic background. C57BL/6J (WT) and TIMP2-/-mice were used in this study. Osmotic pumps loaded with Angiotensin-II (Ang-II) were introduced into a dorsal subcutaneous pocket for delivery at 250 ng. kg-1. min-1. Pumps loaded with saline served as controls for both groups. Blood pressure, renal vascular blood flow, renal vascular density, collagen and elastin deposition, oxidative stress and tissue levels of MMP-2 and MMP-9 were determined.
Results: TIMP2-/- mice had higher baseline mean blood pressure (130.5±6.4 mm Hg) compared to WT mice (111.07±7.3 mm Hg). After 4 weeks of Ang-II treatment, mean arterial pressure increased to 150.33±11.9 in TIMP2 -/- mice compared to 129.9±5.7 mm Hg in WT mice. The renal cortical blood flow was reduced in TIMP2-/- mice (1125 flux units) compared to WT (1350 flux units) and untreated controls. Barium angiography demonstrated decreased renal vascular density in TIMP2-/- mice compared to WT group. Peri-glomerular and vascular collagen deposition was increased in TIMP2-/- and WT, whereas elastin was reduced and disrupted in TIMP2-/- renal vasculature. Intracellular reactive oxygen species production was predominant in TIMP2-/- group than in WT or control animals.
Conclusion: Our results suggest that in Ang-II induced hypertension, renovascular response is strain dependent and TIMP2-/- mice appear to be more susceptible to end organ damage than WT mice.
- © 2012 by American Heart Association, Inc.
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- Abstract 528: Angiotensin-ii Induces Strain-dependent Renovascular Remodeling in MiceSathnur Pushpakumar, Sourav Kundu, Denise Coley, Srikanth Givvimani, Suresh C Tyagi and Utpal SenHypertension. 2012;60:A528, originally published October 14, 2015
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