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

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at maximum constriction [Max Con]) were assessed after 14-day enalapril treatment and 2 to 3 weeks after all drugs were withdrawn.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.