Malignant Hypertension Induction in Cyp1a1-Ren-2 Rats

To induce malignant hypertension, Cyp1a1-Ren-2 rats were fed a diet containing 0.3% I3C for 11 days, which results in the development of malignant hypertension with markedly elevated circulating and tissue ANG II levels as we and others [14 (link)–18 (link)] have demonstrated. The sEH inhibitor c-AUCB was given at a dose of 26 mg/l in drinking water that was prepared freshly every third day as described previously [17 (link)]. Treatment with c-AUCB was started 48 h before feeding the diet with or without I3C. This dose of c-AUCB and the same treatment protocol for c-AUCB were used in our recent study in which we found that it significantly attenuated the development of malignant hypertension in Cyp1a1-Ren-2 transgenic rats and substantially increased tissue concentrations of EETs [17 (link)]. Animals who were exposed to AT₁ receptor blockade received losartan in their drinking water (100 mg/l; Lozap, Zentiva, Prague, Czech Republic); previous studies have demonstrated that this dose of losartan prevents the development of hypertension in this model [25 (link),26 (link)]. On the day of the experiment (day 11 after induction of the renin gene) rats were prepared for acute renal functional studies and for details see the online Data Supplement, http://links.lww.com/HJH/A98.
The following experimental groups of Cyp1a1-Ren-2 transgenic rats were examined:

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Honetschlägerová Z., Sporková A., Kopkan L., Husková Z., Hwang S.H., Hammock B.D., Imig J.D., Kramer H.J., Kujal P., Vernerová Z., Chábová V.Č., Tesař V, & Červenka L. (2011). Inhibition of soluble epoxide hydrolase improves the impaired pressure–natriuresis relationship and attenuates the development of hypertension and hypertension-associated end-organ damage in Cyp1a1-Ren-2 transgenic rats. Journal of hypertension, 29(8), 1590-1601.

Publication 2011

Animals Cyp1a1 Diet Gene induction Hypertension Losartan Malignant hypertension Rats Renin Supplement Tissue Transgenic rats Treatment protocol

Corresponding Organization : Charles University

Other organizations : University of California, Davis, Medical College of Wisconsin, University of Bonn, Pediatric Nephrology of Alabama

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Variable analysis

independent variables

Diet containing 0.3% I3C
Treatment with c-AUCB (26 mg/l in drinking water)
AT1 receptor blockade with losartan (100 mg/l in drinking water)

dependent variables

Development of malignant hypertension
Circulating and tissue ANG II levels
Tissue concentrations of EETs

control variables

Duration of I3C diet (11 days)
Timing of c-AUCB treatment (started 48 h before I3C diet)
Preparation of c-AUCB solution (freshly every third day)

positive control

Previous studies demonstrating that the dose of losartan (100 mg/l) prevents the development of hypertension in this model [25, 26]

negative control

None explicitly mentioned

Annotations

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