Selection Criteria for Drug-Treated Animals in Two-Kidney, One Clip Renal Hypertension

• Published in: Hypertension (Dallas, Tex. 1979) Tex. 1979), 1986-08, Vol.8 (8), p.700-705
• Main Authors: Smith, Shirley H, Bishop, Sanford P
• Format: Article
• Language: English
• Subjects: Animals; Antihypertensive agents; Atrophy; Biological and medical sciences; Cardiovascular system; Constriction; Hydralazine - therapeutic use; Hypertension, Renal - drug therapy; Kidney - pathology; Male; Medical sciences; Organ Size; Pharmacology. Drug treatments; Rats; Rats, Inbred Strains; Spironolactone - therapeutic use
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.8.8.700

The two-kidney, one clip (2K1C) model of hypertension in the rat does not uniformly result in increased blood pressure. That is, the placement of a clip around one renal artery in a two-kidney rat will usually, but not always, produce hypertension. This is an important problem in studies designed to evaluate the ability of antihypertensive therapy to prevent hypertension. Therefore, an additional objective means other than blood pressure is needed to assess animals that are treated from the outset with antihypertensive therapy. The purpose of this study was to correlate the relative fresh weights of left (clipped)/right (nonclipped) kidneys (LWRK) with tail-cuff systolic blood pressure in the 2K1C model of renal hypertension and to identify an LWRK range that would exclude the animals least likely to become hypertensive (failures of the clipping procedure). On a scale of 0.0 to 1.0, an LK/RK ratio of 0.0 was present when the clipped kidney was completely infarcted or atrophied and a ratio of 1.0 was present when the clip did not cause sufficient renal artery stenosis to alter kidney weight. In a series of 72 untreated 2K1C male Sprague-Dawley rats examined 6 to 8 weeks after clipping, 100% of the animals with an LWRK ratio of 0.5 to 0.8 (n = 19) and 75% with an LK/RK ratio of 0.4 to 0.9 (n = 38) had a blood pressure greater than 150 mm Hg. Less than 50% with an LK/RK ratio below 0.4 or above 0.9 (n = 34) were hypertensive. Two 2K1C groups treated with hydralazine (n = 32) or spironolactone (n = 24) were compared with the untreated 2K1C model, and the mean blood pressure of each group was found to be underestimated if the elimination criteria (LK/RK ratio, 0.4–0.9) were not applied. These results indicate that LWRK ratios provide an objective means to compare treatment groups and to evaluate whether a given 2K1C animal would have become hypertensive, had it not been treated with antihypertensive therapy.