Combined treatment with ibuprofen and the AT(1) receptor antagonist candesartan in young spontaneously hypertensive rats

The current study was conducted to determine the potential influence of ibu profen on the renal and systemic response to AT(1) receptor blockade in con scious rats developing spontaneous hypertension. Experiments used spontaneo usly hypertensive rats (SHR) during the early developmental phase of hypert ension (6 to 7 wk old). Six groups of rats were given the following during a 2-wk treatment protocol: (1) candesartan cilexetil (AT(1) receptor antago nist) at 1 mg/kg body wt per d; (2) candesartan cilexetil at 10 mg/kg per d ; (3) ibuprofen at 30 mg/kg per d; (4) a combination of candesartan cilexet il at 1 mg/kg per d + ibuprofen; (5) candesartan cilexetil at 10 mg/kg per d + ibuprofen; and (6) untreated (controls). All compounds were added to th e drinking water at concentrations adjusted to maintain the desired dosage, In the young untreated SHR, systolic arterial pressure significantly incre ased from 134 +/- 4 to 170 +/- 11 mmHg. Candesartan at 1 mg/kg per d preven ted any increase in arterial pressure (131 +/- 5 mmHg at week 0 versus 131 +/- 4 mmHg at week 2). At a dose of 10 mg/kg per d, candesartan lowered art erial pressure from 131 +/- 2 to 91 +/- 4, mmMg. Ibuprofen treatment alone had no effect on the increase in arterial pressure observed in young SHR ov er the study period, and had no effect on the changes produced by candesart an at either dose. In the two groups of rats receiving candesartan at 10 mg /kg per ii (with and without ibuprofen), a significant increase in urine vo lume and water intake was observed; urine volume rose from 9.5 +/- 1.0 to 2 2.9 +/- 1.1 ml/d in rats given only candesartan and from 11.5 +/- 0.7 to 22 .0 +/- 0.6 ml/d in rats given candesartan + ibuprofen. Urine volume and wat er intake were unchanged in all other groups. These effects on water handli ng are consistent with previous findings that chronic angiotensin II inhibi tion inhibits water reabsorption in the kidney. These results demonstrate t hat nonsteroidal anti-inflammatory drug treatment has no effect on the anti hypertensive efficacy and diuretic effects of AT(1) receptor blockade in ra ts developing hypertension.