title: Effects of nicotine administration in a mouse model of familial hypertrophic cardiomyopathy, α-tropomyosin D175N.
abstract: The effects of nicotine (NIC) on normal hearts are fairly well established, yet its effects on hearts displaying familial hypertrophic cardiomyopathy have not been tested. We studied both the acute and chronic effects of NIC on a transgenic (TG) mouse model of FHC caused by a mutation in α-tropomyosin (Tm; i.e., α-Tm D175N TG, or Tm175). For acute effects, intravenously injected NIC increased heart rate, left ventricular (LV) pressure, and the maximal rate of LV pressure increase (+dP/dt) in non-TG (NTG) and Tm175 mice; however, Tm175 showed a significantly smaller increase in the maximal rate of LV pressure decrease (-dP/dt) compared with NTGs. Western blots revealed phosphorylation of phospholamban Ser16 and Thr17 residue increased in NTG mice following NIC injection but not in Tm175 mice. In contrast, phosphorylation of troponin I at serine residues 23 and 24 increased equally in both NTG and Tm175. Thus the attenuated increase in relaxation in Tm175 mice following acute NIC appears to result primarily from attenuated phospholamban phosphorylation. Chronic NIC administration (equivalent to smoking 2 packs of cigarettes/day for 4 mo) also increased +dP/dt in NTG and Tm175 mice compared with chronic saline. However, chronic NIC had little effect on heart rate, LV pressure, -dP/dt, LV wall and chamber dimensions, or collagen content for either group of mice.
authors: Department of Physiology and Biophysics, Section of Cardiology, Center for Cardiovascular Research, University of Illinois at Chicago, Chicago, Illinois 60612, USA.
authors: Robert D
authors: RD
authors: Gaffin
authors: Shamim A K
authors: SA
authors: Chowdhury
authors: Marco S L
authors: MS
authors: Alves
authors: Fernando A L
authors: FA
authors: Dias
authors: Cibele T D
authors: CT
authors: Ribeiro
authors: Rosalvo T H
authors: RT
authors: Fogaca
authors: David F
authors: DF
authors: Wieczorek
authors: Beata M
authors: BM
authors: Wolska
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D020013:Calcium Signaling / Q000187:drug effects; D002135:Calcium-Binding Proteins / Q000378:metabolism; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D002469:Cell Separation; D003094:Collagen / Q000378:metabolism; D004452:Echocardiography; D005260:Female; D005456:Fluorescent Dyes; D016257:Fura-2; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D051379:Mice; D009200:Myocardial Contraction / Q000187:drug effects; D009206:Myocardium / Q000378:metabolism; D032383:Myocytes, Cardiac / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000494:pharmacology*; D014335:Tropomyosin / Q000235:genetics*; D016277:Ventricular Function, Left / Q000502:physiology; D020257:Ventricular Remodeling / Q000187:drug effects; D000099211:Phospholamban
chemical_list: D002135:Calcium-Binding Proteins; D003094:Collagen; D005456:Fluorescent Dyes; D016257:Fura-2; D009538:Nicotine; D018722:Nicotinic Agonists; D014335:Tropomyosin; D000099211:Phospholamban