What question did this study set out to answer?

To investigate whether exogenous and endogenous Angiotensin II modulates TIMP-2 expression in rat aortic smooth muscle cells in vivo independently of elevated blood pressure.

January 25, 2007Clinical and Experimental Pharmacology and Physiology

Angiotensin Ii Increases Tissue‐specific Inhibitor of Metalloproteinase‐2 Expression in Rat Aortic Smooth Muscle Cells in Vivo: Evidence of a Pressure‐independent Effect

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Population

Sprague-Dawley rats and renovascular hypertensive rats

Comparison

Exogenous Angiotensin II with or without… vs Normal saline or sham-clipping

Design

Preclinical

Follow-up

1 week (for exogenous model)

Authors

GCGiovanna CastoldiUniversity of Milano-Bicocca CGCira Di GioiaUniversità Cattolica del Sacro Cuore CTC. TravagliniNewcastle University

Discussion

Member takes

Implication

Should not alter ARB use in hypertension; leaves open TIMP-2's role in human vascular remodeling.

Key Points

To investigate whether exogenous and endogenous Angiotensin II modulates TIMP-2 expression in rat aortic smooth muscle cells in vivo independently of elevated blood pressure.
Infused Sprague-Dawley rats continuously with Angiotensin II (200 ng/kg per min), Angiotensin II plus losartan (10 mg/kg per day), or normal saline subcutaneously via osmotic minipumps for 1 week.
Evaluated endogenous Angiotensin II using two-kidney, one-clip (2K1C) and one-kidney, one-clip (1K1C) renovascular hypertension models alongside sham-clipped controls.
Assessed systolic blood pressure by the tail-cuff method, plasma renin activity by radioimmunoassay, and aortic TIMP-2 mRNA and protein levels by PCR, northern blotting, and immunohistochemistry.
Exogenous Angiotensin II significantly increased systolic blood pressure (P = 0.02) and aortic TIMP-2 expression (P = 0.01) relative to saline controls, both of which were completely prevented by losartan.
Systolic blood pressure was elevated in both 2K1C and 1K1C rats compared to shams (P < 0.0001), but plasma renin activity (P < 0.01) and aortic TIMP-2 expression (P < 0.05) were elevated exclusively in 2K1C rats.

Structured PICO

Population

Sprague-Dawley rats and renovascular hypertensive rats (two kidney, one clip [2K1C] and one kidney, one clip [1K1C] models)

Intervention

Exogenous Angiotensin II (200 ng/kg per min, s.c.) with or without losartan (10 mg/kg per day, s.c.) for 1 week, or endogenous Angiotensin II (via 2K1C/1K1C models)

Comparator

Normal saline (for exogenous model) or sham-clipping (for endogenous model)

Outcome

Aortic TIMP-2 mRNA and protein expressionsurrogate

Angiotensin II increases TIMP-2 expression in rat aortic smooth muscle cells in vivo via AT1 receptors, independent of its blood pressure-raising effects.

Cite This Study

Castoldi et al. (2007) studied this question.

synapsesocial.com/papers/6a729916b27f15817828133e https://doi.org/10.1111/j.1440-1681.2007.04573.x

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Angiotensin Ii Increases Tissue‐specific Inhibitor of Metalloproteinase‐2 Expression in Rat Aortic Smooth Muscle Cells in Vivo: Evidence of a Pressure‐independent Effect

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

Angiotensin Ii Increases Tissue‐specific Inhibitor of Metalloproteinase‐2 Expression in Rat Aortic Smooth Muscle Cells in Vivo: Evidence of a Pressure‐independent Effect

Discussion

Member takes

Implication

Key Points

Structured PICO

Cite This Study

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