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:
The following experimental groups of Cyp1a1-Ren-2 transgenic rats were examined: