Premium
Cardiac autonomic function in mice expressing dominant‐negative mutation of PPAR‐gamma (PPARG) in vascular smooth muscle
Author(s) -
Borges Giulianna da Rocha,
Sigmund Curt D
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.lb140
Subject(s) - medicine , endocrinology , baroreflex , heart rate , tachycardia , cardiac function curve , blood pressure , vascular smooth muscle , basal (medicine) , propranolol , cardiology , heart failure , smooth muscle , insulin
Mice expressing dominant‐negative PPARG in vascular smooth muscle (S‐P467L) exhibited vascular dysfunction, hypertension and tachycardia. We hypothesize that a high sympathetic outflow contributes to cardiovascular dysfunction observed in these mice. S‐P467L and non‐transgenic (NT) littermates were instrumented with radiotelemeters. Basal arterial pressure and heart rate (HR) were continuously recorded. Spontaneous baroreflex (BR) sensitivity was determined using the sequence method. S‐P467L mice exhibited hypertension (116±10 vs 101±3 mmHg) and tachycardia (578±10 vs 487±10 bpm) compared with NT. S‐P467L mice showed an elevated cardiac sympathetic tone, as demonstrated by increased bradycardic response to propranolol (‐102±20 vs ‐43±8 bpm) and a decreased cardiac vagal tone as characterized by decreased tachycardic response to methyl‐atropine (44±12 vs 78±8 bpm). The intrinsic HR, calculated after blockade of vagal and sympathetic outflow to the heart, was elevated in S‐P467L mice compared to NT (511±11 vs 476±11 bpm). BR function was also impaired in S‐P467L mice as shown by the decreased gain (1.82±0.26 vs 2.95±0.34 ms/mmHg) and BR effectiveness index (5±1 vs 8.2±0.7%). These results suggest that the cardiac dysfunction caused by the interference with PPARG in vascular smooth muscle could be caused by a combination of factors such as autonomic imbalance, impaired BR and increased intrinsic HR.