Rapid severe hypertension and organ damage in two-kidney two-clip rats produced by different sizes of clips

Abstract

Background: The two-kidney two-clip (2K2C) rat model is widely used in hypertension, stroke, and drug studies. However, knowledge of this model is quite limited.

Methods: In this study, U-shaped silver clips with inner diameters of 0.3, 0.25, and 0.2 mm were used to narrow bilateral renal arteries, inducing different extents of blood flow reduction for preparing 2K2C rats. Blood pressure (BP) was continuously measured during 2K2C procedures until 10 h after 2K2C, and long-term assessments of BP, organ damage, and serum biochemistry were performed at 1, 2, 4, and 6 weeks.

Results: BP increased immediately when the 2K2C rats regained consciousness from anesthesia, with a 100% incidence of hypertension on the day of operation, and increased to a plateau at 2 weeks for 0.2 mm clips (248 mmHg), 4 weeks for 0.25 mm clips (219 mmHg), and perhaps 6 weeks for 0.3 mm clips (206 mmHg). BP levels displayed a negative correlation with clip sizes. Organ damage, including aortic and cardiac hypertrophy, cerebrovascular and cardiovascular injury, and renal atrophy or compensatory enlargement, occurred as early as 1 or 2 weeks after 2K2C. Routine serum biochemistry indicated organ dysfunction primarily at 4–6 weeks in 0.2 mm clips, whereas aspartate aminotransferase appeared a sensitive biomarker for early organ damage.

Conclusion: 2K2C can produce severe hypertension and multi-organ damage in a short time. 2K2C rats in 0.2 mm clips can be used as a hypertensive emergency model. This study provides crucial insights for guiding the development of targeted interventions.

Keywords

hypertension / organ damage / renal artery stenosis / renin-angiotensin-aldosterone system / two-kidney two-clip

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