What is the clinical evidence from this study?

Study design: Other. Population: Angiotensin II slow pressor response. Intervention: Angiotensin II vs. Vehicle. Primary outcome: Mean arterial pressure (MAP) at 14 days (p=<0.001).

December 1, 2002

A Mouse Model of Angiotensin II Slow Pressor Response

Q: What are the key findings of this study?

Subcutaneous infusion of Angiotensin II at 400 ng/kg/min in mice significantly increased mean arterial pressure to 100 mmHg compared to 85 mmHg with vehicle by day 14 (P<0.001).

Key Result

Subcutaneous infusion of Angiotensin II at 400 ng/kg/min in mice significantly increased mean arterial pressure to 100 mmHg compared to 85 mmHg with vehicle by day 14 (P<0.001).

Structured PICO

Population

Mice infused with graded doses of angiotensin II to study the slow pressor response and oxidative stress over 14 days.

Intervention

Subcutaneous infusion of angiotensin II (AngII) at graded doses (200, 400, and 1000 ng/kg/min) with or without the superoxide dismutase mimetic tempol

Comparator

Vehicle

Outcome

Blood pressure (systolic blood pressure and mean arterial pressure) and renal functional response (glomerular filtration rate, filtration fraction, renal vascular resistance, and renal excretion of 8-iso PGF2alpha)surrogate

The AngII-infused mouse is a valid model for the slow pressor response, demonstrating that increased oxidative stress mediates the delayed rise in blood pressure and renal vascular resistance.

Main Result

Absolute Event Rate: 100% vs 85%

p-value: p=<0.001

Abstract

ABSTRACT. The slow pressor response to prolonged infusions of angiotensin II (AngII) entails a delayed rise in BP. This study investigated the hypothesis that the response depends on the generation of oxidative stress. The BP and renal functional response of mice to graded doses (200, 400, and 1000 ng. kg(-1). min(-1)) of subcutaneously infused AngII was studied. The SBP of conscious mice increased by day 3 at AngII1000 but showed a delayed rise by days 9 to 13 (slow pressor response) at the lower rates of AngII infusion. By day 13, there was a graded increase in SBP with the rate of AngII infusion (Vehicle, -2.6 +/- 2.6%; AngII200, +14.1 +/- 5.0%; AngII400, +31.9 +/- 1.9%; AngII1000, +43.2 +/- 5.5%). The MAP measured under anesthesia rose significantly (P < 0.001) with AngII400 at 14 d (Vehicle, 85 +/- 2 mmHg; AngII400, 100 +/- 3 mmHg). When studied at day 6, the MAP of AngII400 rats was not elevated (88 +/- 2 mmHg; NS versus vehicle), yet the GFR was higher (1.05 +/- 0.05 versus 1.25 +/- 0.05 ml. min(-1). g(-1); P < 0.05) accompanied by an increase in the filtration fraction (FF) (28.8 +/- 1.2 versus 37.2 +/- 0.8%; P < 0.001). From day 6 through day 14, the MAP had increased (P < 0.01) in AngII400, accompanied by a significant reduction in GFR to 1.05 +/- 0.04 ml. min(-1). g(-1) (P < 0.01) and elevation of renal vascular resistance (RVR) (day 6 versus day 14, 15.3 +/- 0.6 versus 19.2 +/- 1.2 mmHg. ml(-1). min(-1). g(-1); P < 0.05). Renal excretion of 8-iso PGF(2alpha) was increased in AngII400 group at day 12 (2.52 +/- 0.35 versus 5.85 +/- 0.78 pg. day(-1); P < 0.01). The permeant superoxide dismutase mimetic tempol reduced the effects of AngII400 on the SBP (-1.7 +/- 5.8%; P < 0.01), the MAP (87 +/- 4 mmHg; P < 0.01), and the RVR (15.2 +/- 0.5 mmHg. ml(-1). min(-1). g(-1); P < 0.05) at day 14 and the renal 8-iso PGF(2alpha) excretion (3.53 +/- 0.71 pg. d(-1); P < 0.05) at day 12. It is concluded that the AngII infused mouse is a valid model for the slow pressor response. There is an early rise in GFR and FF, consistent with increased postglomerular vascular resistance and a late rise in RVR with a fall in GFR, consistent with increased preglomerular vascular resistance that is accompanied by a rise in BP. There is evidence of increased oxidative stress that is implicated in the increase in the BP and RVR in this model.

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