Effects of nicotine administration in a mouse model of familial hypertrophic cardiomyopathy, α-tropomyosin D175N

Abstract

Gaffin RD, Chowdhury SA, Alves MS, Dias FA, Ribeiro CT, Fogaca RT, Wieczorek DF, Wolska BM. Effects of nicotine administration in a mouse model of familial hypertrophic cardiomyopathy, ␣-tropomyosin D175N. Am J Physiol Heart Circ Physiol 301: H1646-H1655, 2011. First published July 8, 2011 doi:10.1152/ajpheart.00277.2010.-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 ␣-tropomyosin (Tm; i.e., ␣-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 (ϩdP/dt) in non-TG (NTG) and Tm175 mice; however, Tm175 showed a significantly smaller increase in the maximal rate of LV pressure decrease (ϪdP/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 ϩdP/dt in NTG and Tm175 mice compared with chronic saline. However, chronic NIC had little effect on heart rate, LV pressure, ϪdP/dt, LV wall and chamber dimensions, or collagen content for either group of mice. in vivo pressure recordings; phospholamban; phosphorylation; cardiac remodeling NUMEROUS STUDIES HAVE TESTED the adverse effects of smoking on cardiovascular health in both healthy and diseased hearts (reviewed in Ref. 5). However, many of these adverse effects may be attributable to the "tar" and/or carbon monoxide in cigarette smoke. Nicotine (NIC) is widely heralded as the addictive component of cigarettes, cigars, and pipe tobacco (6, 7), and its impact alone on cardiovascular disease is gaining more recognition due to the presence of a myriad of smokeless tobacco products (reviewed in Ref. 46). Yet, to the best of our knowledge, its impact on familial hypertrophic cardiomyopathies (FHCs) has not been studied.FHCs are defined as autosomal dominant disorders that result in numerous cardiac maladies including hypertrophy, diastolic dysfunction, fibrosis, myocyte disarray, and arrhythmias (9, 34). They are considered to be a leading cause of sudden cardiac death in young athletes (10,32,35) and have a prevalence of 1:500 when familial and nonfamilial forms are considered together (16). FHCs have been described as a "disease of the sarcomere" since the majority of cases have been linked to mutations in sarcomeric proteins such as myosin heavy chain, troponin T, myosin-binding protein C, and ␣-tropomyosin (Tm; Refs. 9, 21, 54, 64). We have ...

Peroxisome proliferator-activated receptor-α expression induces alterations in cardiac myofilaments in a pressure-overload model of hypertrophy

“…Echocardiography. Echocardiography was performed on anesthetized mice (3.5% isoflurane with 100% oxygen induction with 1.5% isoflurane in 100% oxygen maintenance) using a VisualSonics' Vevo 2100 ultrasound machine and MS550D (40 MHz) transducer as previously reported (2,28). Transthoracic B-mode, M-mode, pulsed Doppler, and tissue Doppler images were obtained from the parasternal short-axis view (systolic and morphology parameters) and the apical view (diastolic parameters).…”

Potential Contribution of Aromatase Inhibition to the Effects of Nicotine and Related Compounds on the Brain

“…In a study of persistent pregnant smokers, the smokers reported higher prenatal stress and depression than non-persistent smokers or non-smokers (Eiden et al, 2011 ). Women were also found to be more vulnerable to the depressive symptoms of nicotine withdrawal (Gaffin et al, 2011 ). Acutely, nicotine has been found to be more anxiolytic in female than in male rats (Harrod et al, 2004 ), corroborating human studies which also document that females are more susceptible to the effects of nicotine on anxiety (Pogun and Yararbas, 2009 ).…”