Renovascular remodeling in Angiotensin‐II induced hypertension is strain–dependent

Abstract

Hypertension is a recognized cause of chronic kidney disease and end‐stage renal dysfunction. Sustained hypertension induces renovascular remodeling in both intra and extra‐renal vasculature and alters extracellular matrix (ECM) components. Our objective was to define renovascular phenotypes in agonist induced hypertension in different strains of mice. Osmotic pumps loaded with Angiotensin‐II (Ang‐II) were inserted subcutaneously into C57BL/6J (WT), TIMP2−/−, and C3H/HeJ mice for delivery at 250 ng. kg‐1. min‐1.ResultsAng‐II induced higher blood pressures in WT and TIMP2−/− mice compared to C3H mice. Blood flow across renal artery and aorta was decreased by 33% in TIMP2−/− mice; whereas, in WT and C3H mice, flow decreased by 23 and 20% (aorta) and 19 and 10% (renal artery) compared to untreated controls. Barium microangiography showed decreased renal vascular density in TIMP2−/− and WT groups than in C3H. Peri‐glomerular and vascular collagen deposition was increased in TIMP2−/− and WT compared to C3H. Elastin deposition, however, was predominant in WT than in the other groups. Intracellular reactive oxygen species production was low in C3H mice, increased moderately in WT and was twice as high in TIMP2−/− than in C3H.ConclusionsOur results suggest that in Ang‐II induced hypertension, renovascular response is strain dependent indicating a genetic basis for disease susceptibility.