title: Basal and ethanol-induced cardiac contractile response in lean and obese Zucker rat hearts.
abstract: Obesity plays a pivotal role in metabolic and cardiovascular diseases. Certain types of obesity may be related to alcohol ingestion, which itself leads to impaired cardiac function. This study analyzed basal and ethanol-induced cardiac contractile response using left-ventricular papillary muscles and myocytes from lean and obese Zucker rats. Contractile properties analyzed include: peak tension development (PTD), peak shortening amplitude (PS), time to PTD/PS (TPT/TPS), time to 90% relaxation/relengthening (RT(90)/TR(90)) and maximal velocities of contraction/shortening and relaxation/relengthening (+/-VT and +/-dL/dt). Intracellular Ca(2+) transients were measured as fura-2 fluorescence intensity (DeltaFFI) changes and fluorescence decay time (FDT). In papillary muscles from obese rats, the baseline TPT and RT(90) were significantly prolonged accompanied with low to normal PTD and +/-VT compared to those in lean rats. Muscles from obese hearts also exhibited reduced responsiveness to postrest potentiation, increase in extracellular Ca(2+) concentration, and norepinephrine. By contrast, in isolated myocytes, obesity reduced PS associated with a significant prolonged TR(90), normal TPS and +/-dL/dt. Intracellular Ca(2+) recording revealed decreased resting Ca(2+) levels and prolonged FDT. Acute ethanol exposure (80-640 mg/dl) caused comparable concentration-dependent inhibitions of PTD/PS and DeltaFFI, associated with reduced +/-VT in both groups. Collectively, these results suggest altered cardiac contractile function and unchanged ethanol-induced depression in obesity.
authors.affiliation: Department of Pharmacology, Physiology, and Therapeutics, University of North Dakota School of Medicine, Grand Forks, ND 58203, USA. jren@medicine.nodak.edu
authors.forename: J
authors.initials: J
authors.lastname: Ren
authors.forename: M F
authors.initials: MF
authors.lastname: Walsh
authors.forename: L
authors.initials: L
authors.lastname: Jefferson
authors.forename: M
authors.initials: M
authors.lastname: Natavio
authors.forename: K J
authors.initials: KJ
authors.lastname: Ilg
authors.forename: J R
authors.initials: JR
authors.lastname: Sowers
authors.forename: R A
authors.initials: RA
authors.lastname: Brown
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D002118:Calcium / Q000378:metabolism / Q000494:pharmacology; D002316:Cardiotonic Agents / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology*; D005260:Female; D005453:Fluorescence; D006352:Heart Ventricles / Q000166:cytology / Q000187:drug effects*; D017379:Hypertrophy, Left Ventricular / Q000503:physiopathology; D066298:In Vitro Techniques; D007545:Isoproterenol / Q000494:pharmacology; D009200:Myocardial Contraction / Q000187:drug effects*; D009638:Norepinephrine / Q000494:pharmacology; D009765:Obesity / Q000503:physiopathology*; D010210:Papillary Muscles / Q000187:drug effects; D051381:Rats; D011924:Rats, Zucker
chemical_list: D002316:Cardiotonic Agents; D000431:Ethanol; D007545:Isoproterenol; D002118:Calcium; D009638:Norepinephrine