Persistent lowering of arterial pressure after continuous and intermittent therapy

Objective: The present study investigates the impact of antihypertensive treatment on persistent reduction of arterial pressure after cessation of drug treatment. Design and methods: Specifically, adult spontaneously hypertensive rats (SHR) were treated for 6 weeks with inhibitors of the renin-angiotensin system (RAS), or combination therapy (hydralazine, nifedipine, hydrochlorothiazide) and following a 14-week 'drug holiday', were re-treated for 4 weeks. Mean arterial pressure (MAP) was continuously monitored via radiotelemetry. Results: Comparison in the first off-treatment period revealed that RAS inhibitor drugs produced a 16-18% persistent lowering of arterial pressure, whereas the triple therapy induced a 10% lowering of MAP relative to untreated SHR. The drug re-challenge induced a further 9% reduction in the 'off'-treatment level of MAP such that in all treatment groups MAP was reduced by more than 30 mmHg compared with controls. Conclusions: This study provides new evidence that combination therapy, not directly targeting the RAS, can be efficacious in persistently reducing MAP off-treatment. Furthermore, we demonstrated that the 6-week treatment with RAS inhibitors induced equivalent persistent changes as a 10-week treatment. That is, the additional 4 weeks of continuous therapy was ineffective in further altering the off-treatment MAP. In contrast, with the intermittent treatment protocol (the 14-week 'drug holiday') a further effect on persistent lowering of MAP was regained. These findings suggest continuous long-term treatment with antihypertensive drugs may not be the most effective means of reversing underlying circulatory abnormalities and that the introduction of a drug holiday may be beneficial.