title: Angiotensin II maintains, but does not mediate, isoproterenol-induced cardiac hypertrophy in rats.
abstract: The role of angiotensin II (ANG II) in the development of isoproterenol (Iso)-induced cardiac hypertrophy was examined in rats. Iso increased cardiac mass, left ventricular RNA-to-DNA ratio, and the cardiac content of both myosin heavy chain and hydroxyproline in a dose-dependent manner, indicating that Iso-induced cardiac hypertrophy involves growth of both muscle and connective tissue. Cardiac hypertrophy reverted within 11-14 days after cessation of Iso. Propranolol prevented development of Iso-induced cardiac hypertrophy but did not affect the rate of its reversal. The ANG II receptor blocker losartan (Los) did not significantly decrease the hypertrophic response to Iso. Los injected after cessation of Iso dramatically enhanced the reversal of cardiac hypertrophy, even in rats that received Los with Iso during the induction of Iso-induced cardiac hypertrophy. ANG II, injected continuously at a subpressor dose that did not affect heart weight when given alone, inhibited reversal of cardiac hypertrophy when given after cessation of Iso. Los did not significantly affect the induction of the protooncogene c-fos by Iso. We conclude that endogenous ANG II has a major function in maintaining Iso-induced cardiac hypertrophy but does not mediate its induction. This suggests that different interactive stimuli may be required for development of cardiac hypertrophy, i.e., for initiation and for maintenance.
authors.affiliation: Hypertension-Endocrine Branch, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, Maryland 20892.
authors.forename: E
authors.initials: E
authors.lastname: Golomb
authors.forename: Z A
authors.initials: ZA
authors.lastname: Abassi
authors.forename: G
authors.initials: G
authors.lastname: Cuda
authors.forename: M
authors.initials: M
authors.lastname: Stylianou
authors.forename: V R
authors.initials: VR
authors.lastname: Panchal
authors.forename: D
authors.initials: D
authors.lastname: Trachewsky
authors.forename: H R
authors.initials: HR
authors.lastname: Keiser
mesh_terms: D000199:Actins / Q000096:biosynthesis; D000804:Angiotensin II / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001483:Base Sequence; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D006332:Cardiomegaly / Q000139:chemically induced / Q000188:drug therapy / Q000503:physiopathology*; D004247:DNA / Q000378:metabolism; D017931:DNA Primers; D004305:Dose-Response Relationship, Drug; D015870:Gene Expression / Q000187:drug effects; D016762:Genes, fos; D006321:Heart / Q000187:drug effects / Q000503:physiopathology; D006830:Hydralazine / Q000494:pharmacology; D006909:Hydroxyproline / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology*; D007545:Isoproterenol / Q000494:pharmacology*; D007741:Labetalol / Q000494:pharmacology; D019808:Losartan; D008297:Male; D008750:Methyldopa / Q000494:pharmacology; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism; D009218:Myosins / Q000096:biosynthesis; D016133:Polymerase Chain Reaction; D012313:RNA / Q000378:metabolism; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology*; D014158:Transcription, Genetic / Q000187:drug effects
chemical_list: D000199:Actins; D001713:Biphenyl Compounds; D017931:DNA Primers; D007093:Imidazoles; D012333:RNA, Messenger; D013777:Tetrazoles; D000804:Angiotensin II; D006830:Hydralazine; D008750:Methyldopa; D012313:RNA; D004247:DNA; D002216:Captopril; D009218:Myosins; D019808:Losartan; D007545:Isoproterenol; D007741:Labetalol; D006909:Hydroxyproline