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Altered autonomic control in conscious transgenic rabbits with overexpressed cardiac Gs

¹Cardiovascular Research Institute and Department of Cell Biology and Molecular Medicine, University of Medicine and Dentistry of New Jersey, New Jersey Medical School, Newark, New Jersey; and ²Children’s Hospital Medical Center, Cincinnati, Ohio

Submitted 24 July 2006 ; accepted in final form 3 October 2006

Both enhanced sympathetic drive and altered autonomic control are involved in the pathogenesis of heart failure. The goal of the present study was to determine the extent to which chronically enhanced sympathetic drive, in the absence of heart failure, alters reflex autonomic control in conscious, transgenic (TG) rabbits with overexpressed cardiac Gs. Nine TG rabbits and seven wild-type (WT) littermates were instrumented with a left ventricular (LV) pressure micromanometer and arterial catheters and studied in the conscious state. Compared with WT rabbits, LV function was enhanced in TG rabbits, as reflected by increased levels of LV dP/dt (5,600 ± 413 vs. 3,933 ± 161 mmHg/s). Baseline heart rate was also higher (P < 0.05) in conscious TG (247 ± 10 beats/min) than in WT (207 ± 10 beats/min) rabbits and was higher in TG after muscarinic blockade (281 ± 9 vs. 259 ± 8 beats/min) or combined -adrenergic receptor and muscarinic blockade (251 ± 6 vs. 225 ± 9 beats/min). Bradycardia was blunted (P < 0.05), whether induced by intravenous phenylephrine (arterial baroreflex), by cigarette smoke inhalation (nasopharyngeal reflex), or by veratrine administration (Bezold-Jarisch reflex). With veratrine administration, the bradycardia was enhanced in TG for any given decrease in arterial pressure. Thus the chronically enhanced sympathetic drive in TG rabbits with overexpressed cardiac Gs resulted in enhanced LV function and heart rate and impaired reflex autonomic control. The impaired reflex control was generalized, not only affecting the high-pressure arterial baroreflex but also the low-pressure Bezold-Jarisch reflex and the nasopharyngeal reflex.

heart failure; sympathetic tone; vagal nerves; heart rate; left ventricular contractility