Combined treatment with ibuprofen and the AT1 receptor antagonist candesartan in young spontaneously hypertensive rats.
The current study was conducted to determine the potential influence of ibuprofen on the renal and systemic response to AT1 receptor blockade in conscious rats developing spontaneous hypertension. Experiments used spontaneously hypertensive rats (SHR) during the early developmental phase of hypertension (6 to 7 wk old). Six groups of rats were given the following during a 2-wk treatment protocol: (1) candesartan cilexetil (AT1 receptor antagonist) 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 cilexetil 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 the drinking water at concentrations adjusted to maintain the desired dosage. In the young untreated SHR, systolic arterial pressure significantly increased from 134+/-4 to 170+/-11 mmHg. Candesartan at 1 mg/kg per d prevented 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 arterial pressure from 131+/-2 to 91+/-4 mmHg. Ibuprofen treatment alone had no effect on the increase in arterial pressure observed in young SHR over the study period, and had no effect on the changes produced by candesartan at either dose. In the two groups of rats receiving candesartan at 10 mg/kg per d (with and without ibuprofen), a significant increase in urine volume and water intake was observed; urine volume rose from 9.5+/-1.0 to 22.9+/-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 water intake were unchanged in all other groups. These effects on water handling are consistent with previous findings that chronic angiotensin II inhibition inhibits water reabsorption in the kidney. These results demonstrate that nonsteroidal anti-inflammatory drug treatment has no effect on the antihypertensive efficacy and diuretic effects of AT1 receptor blockade in rats developing hypertension.
Pollock
D M
DM
Vascular Biology Center, Medical College of Georgia, Augusta 30912-2500, USA. DPollock@mail.mcg.edu
Morsing
P
P
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000494:pharmacology / Q000627:therapeutic use*; D001562:Benzimidazoles / Q000627:therapeutic use*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D004326:Drinking / Q000187:drug effects; D004359:Drug Therapy, Combination; D004435:Eating / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology / Q000652:urine; D007052:Ibuprofen / Q000494:pharmacology / Q000627:therapeutic use*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012964:Sodium / Q000652:urine; D013777:Tetrazoles / Q000627:therapeutic use*
D057911:Angiotensin Receptor Antagonists; D000894:Anti-Inflammatory Agents, Non-Steroidal; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D013777:Tetrazoles; D012964:Sodium; C081643:candesartan; D007052:Ibuprofen