Key Points
- To assess the blood pressure-lowering and heart rate effects of combined therapy with the AT1 receptor blocker valsartan and the diuretic hydrochlorothiazide in conscious spontaneously hypertensive rats.
- Administered valsartan, hydrochlorothiazide, or benazeprilat alone and in combination continuously for 2 weeks via subcutaneously implanted osmotic minipumps in conscious spontaneously hypertensive rats.
- Continuously recorded mean arterial pressure and heart rate throughout the 2-week infusion period using chronically implanted radiotransmitters.
- Hydrochlorothiazide coadministration potentiated blood pressure lowering, displaying additive effects at 1 mg/kg/day valsartan and synergistic reductions at 3 mg/kg/day valsartan combined with 10 mg/kg/day hydrochlorothiazide.
- Marked reductions in blood pressure during combination therapy triggered only a transient elevation in heart rate.
- Benazeprilat coadministered with hydrochlorothiazide similarly produced additive blood pressure reductions at 3 mg/kg/day hydrochlorothiazide and synergistic reductions at higher diuretic doses.
Structured PICO
Does the combination of valsartan and hydrochlorothiazide reduce blood pressure more effectively than either agent alone in spontaneously hypertensive rats?
PPopulationConscious spontaneously hypertensive rats (SHR)
IInterventionValsartan (1 or 3 mg/kg/day) combined with hydrochlorothiazide (3 or 10 mg/kg/day) administered continuously via subcutaneously implanted osmotic minipumps for 2 weeks
CComparatorValsartan alone or hydrochlorothiazide alone
OOutcomeMean arterial pressuresurrogate
Coadministration of valsartan and hydrochlorothiazide produces additive to synergistic blood pressure lowering effects in spontaneously hypertensive rats, likely due to diuretic-induced activation of the renin-angiotensin system.