Heart failure (HF) rats: treated for 4 weeks with intracerebroventricular RU28318 (1 μg/hr) had less hypothalamic ACE and AT1-R mRNA and protein, less NAD(P)H-induced superoxide in PVN, fewer excited PVN neurons, and lower plasma NE. RU28318 had no effect on plasma ALDO, or on ACE or AT1-R mRNA expression in brain cortex

Hearts removed from animals were perfused for 30 min and then subjected to 30 min of global ischemia (I) followed by a period of 30 min of reperfusion (R). Drugs were administered for 30 min either during perfusion before ischemia or during reperfusion after ischemia. Drug regimens tested were RU28318 (RU; 10-5 M), Captopril (Capt; 3.6 × 10-4 M), Losartan (Los; 3 × 10-4 M), RU + Capt, RU + Los, Capt + Los, and RU + Capt + Los (Triple). In ischemia/reperfusion- (I/R-) injury, was shown that combination approaches were better where Capt + Los + RU (Triple) therapy used in normal and diabetes. However, combination therapies with ACEI and ARBs are rarely employed in the clinic possibly due to fear over accumulating adverse effects in patients with heart disorders.