title: Apoptosis during regression of cardiac hypertrophy in spontaneously hypertensive rats. Temporal regulation and spatial heterogeneity.
abstract: We previously reported that increased apoptosis participates in the regression of aortic hypertrophy in spontaneously hypertensive rats. To further document the potential role of apoptosis in cardiovascular therapy, we examined apoptosis during regression of hypertrophy in the heart of spontaneously hypertensive rats receiving the antihypertensive drug enalapril (30 mg. kg(-1). d(-1)), losartan (30 mg. kg(-1). d(-1)), nifedipine (35 mg. kg(-1). d(-1)), hydralazine (40 mg. kg(-1). d(-1)), propranolol (50 mg. kg(-1). d(-1)), or hydrochlorothiazide (75 mg. kg(-1). d(-1)) for 1 to 4 weeks, starting at 10 to 11 weeks of age. Systolic blood pressure and heart rate were measured by the tail-cuff method. Markers of apoptosis included oligonucleosomal DNA fragmentation in extracted cardiac DNA or in situ in ventricular cross sections labeled with terminal deoxynucleotidyl transferase. Cardiac DNA synthesis was evaluated by [(3)H]-thymidine incorporation in vivo. All drugs reduced cardiac workload, defined as the product of blood pressure and heart rate, by >20% at 4 weeks. However, only nifedipine, enalapril, losartan, and propranolol reduced cardiac mass (>19%) within 4 weeks. Regression of cardiac hypertrophy was accompanied by a 50% to 300% increase in DNA fragmentation and a >20% reduction in DNA synthesis, resulting in a >20% reduction in cardiac DNA content after 4 weeks. Apoptosis induction occurred early and was transient within 4 weeks of nifedipine, enalapril, or losartan administration. With all regression-inducing drugs, the increase in DNA fragmentation occurred mainly in the subepicardium. Thus, transient induction of apoptosis in the subepicardium appears to be a characteristic feature of the early response to drug-induced regression of cardiac hypertrophy in spontaneously hypertensive rats.
authors.affiliation: University of Montreal Hospital (CHUM) Research Center, Departments of Pharmacology and Medicine and the Faculty of Pharmacy, University of Montreal, Quebec, Canada.
authors.forename: B S
authors.initials: BS
authors.lastname: Tea
authors.forename: T V
authors.initials: TV
authors.lastname: Dam
authors.forename: P
authors.initials: P
authors.lastname: Moreau
authors.forename: P
authors.initials: P
authors.lastname: Hamet
authors.forename: D
authors.initials: D
authors.lastname: deBlois
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D057911:Angiotensin Receptor Antagonists; 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*; D017209:Apoptosis; D002121:Calcium Channel Blockers / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D006332:Cardiomegaly / Q000188:drug therapy* / Q000503:physiopathology*; D004247:DNA / Q000032:analysis / Q000096:biosynthesis / Q000187:drug effects; D053938:DNA Fragmentation; D003627:Data Interpretation, Statistical; D004656:Enalapril / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D006439:Hemodynamics / Q000187:drug effects; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D019808:Losartan / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D009543:Nifedipine / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011433:Propranolol / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D013997:Time Factors
chemical_list: D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D006830:Hydralazine; D004656:Enalapril; D004247:DNA; D011433:Propranolol; D009543:Nifedipine; D019808:Losartan