title: 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 x kg(-1) x d(-1)) with regular (ENAL, 0.4%) or low salt (ELS, 0.04%) diets, or a triple therapy (Triple: hydralazine 45 mg x kg(-1) x 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at maximum constriction [Max Con]) were assessed after 14-day enalapril treatment and 2 to 3 weeks after all drugs were withdrawn.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 downward arrow 12+/-4.6%, ELS downward arrow 16+/-2.6%, Triple downward arrow 5+/-4.17%). During treatment (14 days) the enalapril group had significant changes in the index of medial bulk (Max Con downward arrow 15+/-2.6%), but only minimal changes in lumen properties (Max Dil downward arrow 3+/-6.5%, NS). After stopping therapy, vascular properties at Max Dil were significantly decreased only in the 2 enalapril groups (ENAL downward arrow 15+/-7.9%, P<0.05; ELS downward arrow 9+/-6.0%, P<0.05; Triple downward arrow 2+/-9.8%, NS), whereas Max Con was significantly decreased in all groups (ENAL downward arrow 12+/-8.0%, ELS downward arrow 16+/-6.1%, Triple downward 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.
authors.affiliation: Department of Pharmacology and Toxicology, Queen's University, Kingston, Ontario, Canada, K7L 3N6.
authors.forename: Taben M
authors.initials: TM
authors.lastname: Hale
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Shoichet
authors.forename: Terri L
authors.initials: TL
authors.lastname: Bushfield
authors.forename: Michael A
authors.initials: MA
authors.lastname: Adams
mesh_terms: D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D001794:Blood Pressure / Q000187:drug effects*; D001808:Blood Vessels / Q000473:pathology / Q000503:physiopathology; D004359:Drug Therapy, Combination; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006614:Hindlimb / Q000098:blood supply; D006973:Hypertension / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D017379:Hypertrophy, Left Ventricular / Q000175:diagnosis; D007700:Kinetics; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism; D014655:Vascular Resistance / Q000187:drug effects*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004656:Enalapril; D014568:Urokinase-Type Plasminogen Activator