Time course of vascular structural changes during and after short-term antihypertensive treatment

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maximum constriction [ Max Con]) were assessed after 14-day enalapril treatment and 2 to 3 weeks after all drugs were withdrawn.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 down arrow 12 +/- 4.6%, ELS down arrow 16 +/- 2.6%, Triple down arrow 5 +/- 4.17%). During treatment ( 14 days) the enalapril group had significant changes in the index of medial bulk (Max Con down arrow15 +/- 2.6%), but only minimal changes in lumen properties (Max Dil down arrow3 +/- 6.5%, NS). After stopping therapy, vascular properties at Max Dil were significantly decreased only in the 2 enalapril groups (ENAL down arrow15 +/- 7.9%, P < 0.05; ELS ↓9 +/- 6.0%, P < 0.05; Triple down arrow2 +/- 9.8%, NS), whereas Max Con was significantly decreased in all groups (ENAL down arrow12 +/- 8.0%, ELS down arrow16 +/- 6.1%, Triple down arrow 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.