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Age exacerbates chronic catecholamine‐induced impairments in contractile reserve
Author(s) -
Liles John Thomas,
Ida Kevin,
Joly Kristin,
Chapo Joseph,
Peng Yanyu,
Plato Craig F
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.812.6
Subject(s) - medicine , endocrinology , inotrope , catecholamine , agonist , muscle hypertrophy , basal (medicine) , isoprenaline , apoptosis , heart failure , calcium , receptor , chemistry , stimulation , biochemistry , insulin
Heart failure is more prevalent and impaired contractile reserve develops with advancing age. This study evaluated whether adult, non‐senescent (A) rats (18 wk) are more susceptible to detrimental effects of chronic isoproterenol (ISO) administration than younger (Y) rats (12 wk). Rats received daily injections of ISO (0.1 mg/kg, s.c.) or vehicle (V) for three weeks. V‐Y rats had greater baseline +dP/dt max compared to V‐A rats, as well as to both ISO‐Y and ISO‐A rats (6812±264 vs. 5841±239, 5089±223, and 5356±197 mmHG/sec, respectively). ISO induced a greater impairment in contractile reserve (Δ +dP/dt max ) in A than in Y to two mechanistically distinct inotropes (digoxin, milrinone; 20 ‐ 200 ul/kg/min), while basal and agonist‐induced changes in heart rate, MAP, or SAP were not different across groups. ISO also induced greater increases in cardiac hypertrophy (LV index: 33±3 % vs. 22±5 %), caspase‐3 activity (34 % vs. 5%), and β‐MHC mRNA expression (3.7 vs. 1.3 fold induction) in A relative to Y rats. Moreover, ISO decreased expression of the calcium handling protein, SERCA2a, by 55% in A relative to Y rats. These results demonstrate adult rats develop greater impairments in systolic performance than younger rats when exposed to chronic catecholamine excess. Reduced contractile reserve may result from increased β‐MHC expression, increased cardiomyocyte apoptosis/caspase activity, and/or calcium dysregulation.