Published Online
on June 16, 2003

A more recent version of this article appeared on August 1, 2003

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Submitted on April 9, 2003
Revised on May 5, 2003

Time Course of Vascular Structural Changes During and After Short-Term Antihypertensive Treatment

Taben M. Hale; Martin J. Shoichet; Terri L. Bushfield; and Michael A. Adams^*

From the Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada.

^* To whom correspondence should be addressed. E-mail: adams{at}post.queensu.ca.

Abstract--The present study characterized the persistent changes (ie, off-treatment) resulting from short-term antihypertensive treatments on mean arterial pressure (MAP) and structurally based vascular resistance. Rats were treated for 14 days with enalapril (30 mg · kg^-1 · d^-1) with regular (ENAL, 0.4%) or low salt (ELS, 0.04%) diets, or a triple therapy (Triple: hydralazine 45 mg · kg^-1 · d^-1, hydrochlorothiazide 100 mg/L, and nifedipine 200 mg/d). MAP was continuously recorded via radiotelemetry. Structurally based hindlimb vascular resistance properties (resistance at maximum dilation [Max Dil]; resistance at maximum constriction [Max Con]) were assessed after 14-day enalapril treatment and 2 to 3 weeks after all drugs were withdrawn. Aortic urokinase plasminogen activator (uPA) activity was measured by zymography after 14 days of ELS. All treatments induced a significant, persistent decrease in the off-treatment MAP (ENAL 12±4.6%, ELS 16±2.6%, Triple 5±4.17%). During treatment (14 days) the enalapril group had significant changes in the index of medial bulk (Max Con 15±2.6%), but only minimal changes in lumen properties (Max Dil 3±6.5%, NS). After stopping therapy, vascular properties at Max Dil were significantly decreased only in the 2 enalapril groups (ENAL 15±7.9%, P<0.05; ELS 9±6.0%, P<0.05; Triple 2±9.8%, NS), whereas Max Con was significantly decreased in all groups (ENAL 12±8.0%, ELS 16±6.1%, Triple 7±5.4%). At 14 days of ELS treatment, there was increased aortic uPA activity (1.6-fold). The findings reveal that various short-term antihypertensive treatments can produce persistent long-term changes in MAP and vascular structure. Further, the magnitude of the depressor response may be as important in inducing persistent changes as is the removal of angiotensin II.

Key words: rats, inbred SHR • vascular resistance • arterial pressure • antihypertensive agents • hypertension, experimental • sodium, dietary

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