Altered autonomic control in conscious transgenic rabbits with overexpressed cardiac Gsα

Takao Nishizawa, You Tang Shen, Franco Rossi, Chull Hong, Jeffrey Robbins, Yoshihiro Ishikawa, Junichi Sadoshima, Dorothy E. Vatner, Stephen F. Vatner

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

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 Gsα. 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 β-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 Gsα 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.

Original languageEnglish (US)
Pages (from-to)H971-H975
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume292
Issue number2
DOIs
StatePublished - Feb 1 2007

Fingerprint

Reflex
Rabbits
Veratrine
Baroreflex
Bradycardia
Left Ventricular Function
Cholinergic Agents
Arterial Pressure
Heart Failure
Heart Rate
Phenylephrine
Ventricular Pressure
Smoke
Tobacco Products
Adrenergic Receptors
Inhalation
Catheters
Pressure
Drive

All Science Journal Classification (ASJC) codes

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Keywords

  • Heart failure
  • Heart rate
  • Left ventricular contractility
  • Sympathetic tone
  • Vagal nerves

Cite this

Nishizawa, Takao ; Shen, You Tang ; Rossi, Franco ; Hong, Chull ; Robbins, Jeffrey ; Ishikawa, Yoshihiro ; Sadoshima, Junichi ; Vatner, Dorothy E. ; Vatner, Stephen F. / Altered autonomic control in conscious transgenic rabbits with overexpressed cardiac Gsα. In: American Journal of Physiology - Heart and Circulatory Physiology. 2007 ; Vol. 292, No. 2. pp. H971-H975.
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Altered autonomic control in conscious transgenic rabbits with overexpressed cardiac Gsα. / Nishizawa, Takao; Shen, You Tang; Rossi, Franco; Hong, Chull; Robbins, Jeffrey; Ishikawa, Yoshihiro; Sadoshima, Junichi; Vatner, Dorothy E.; Vatner, Stephen F.

In: American Journal of Physiology - Heart and Circulatory Physiology, Vol. 292, No. 2, 01.02.2007, p. H971-H975.

Research output: Contribution to journalArticle

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T1 - Altered autonomic control in conscious transgenic rabbits with overexpressed cardiac Gsα

AU - Nishizawa, Takao

AU - Shen, You Tang

AU - Rossi, Franco

AU - Hong, Chull

AU - Robbins, Jeffrey

AU - Ishikawa, Yoshihiro

AU - Sadoshima, Junichi

AU - Vatner, Dorothy E.

AU - Vatner, Stephen F.

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N2 - 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 Gsα. 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 β-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 Gsα 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.

AB - 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 Gsα. 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 β-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 Gsα 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.

KW - Heart failure

KW - Heart rate

KW - Left ventricular contractility

KW - Sympathetic tone

KW - Vagal nerves

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