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.


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.
Woolard
Jeanette
J
Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.
Hale
Taben M
TM
Bushfield
Terri L
TL
Adams
Michael A
MA
D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D006352:Heart Ventricles / Q000473:pathology; D006830:Hydralazine / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D009543:Nifedipine / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D012084:Renin-Angiotensin System / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D014665:Vasodilator Agents; D006852:Hydrochlorothiazide; D006830:Hydralazine; D004656:Enalapril; D009543:Nifedipine; D019808:Losartan