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(Circulation. 1998;97:2359-2367.)
© 1998 American Heart Association, Inc.

Basic Science Reports

Dual-Tracer Assessment of Coupling Between Cardiac Sympathetic Neuronal Function and Downregulation of ß-Receptors During Development of Hypertensive Heart Failure of Rats

Takashi Nozawa, MD; Akihiko Igawa, MD; Naohiro Yoshida, MD; Masatoshi Maeda, PhD; Minoru Inoue, PhD; Yoshitaka Yamamura, PhD; Hidetsugu Asanoi, MD; ; Hiroshi Inoue, MD

From the 2nd Department of Internal Medicine and Department of Basic Radiology, Toyama Medical and Pharmaceutical University (T.N., A.I., N.Y., M.M., H.A., H.I.); Research Laboratories, Daiichi Radioisotope Laboratory, Ltd, Chiba (M.I.); and Pharmacology, Otsuka Pharmaceutical Co, Ltd, Tokushima (Y.Y.), Japan.

Correspondence to Takashi Nozawa, MD, 2nd Department of Internal Medicine, Toyama Medical and Pharmaceutical University, 2630 Sugitani, Toyama, 930–01 Japan.

Background—Heart failure is associated with activation of the sympathetic nervous system and downregulation of ß-receptors. However, the coupling between cardiac sympathetic neuronal function and the ß-receptor during the development of hypertensive heart failure is not clear.

Methods and Results—We determined cardiac neuronal function and ß-receptors with a dual-tracer method of [¹³¹I]metaiodobenzylguanidine (MIBG) and ¹²⁵I-cyanopindolol (ICYP) in Dahl salt-sensitive (DS) and salt-resistant (DR) rats. The rats were fed an 8% NaCl diet after the age of 6 weeks. Blood pressure was raised to >200 mm Hg at 12 weeks in DS rats and remained elevated until 18 weeks, but only slightly in DR rats. Left ventricular (LV) function of DS rats was preserved at 12 weeks but deteriorated at 18 weeks. Despite a 56% reduction of cardiac norepinephrine (NE) content at 12 weeks in DS rats, neither MIBG nor ICYP uptake in DS rats was different from that of DR rats. At 18 weeks, both MIBG and ICYP uptakes decreased, by 52% and 39%, respectively, in association with 71% reduction of cardiac NE, in DS rats. MIBG uptake of the LV was homogeneous at 6 weeks but was lower in the LV endocardial regions at 18 weeks in DS rats.

Conclusions—The present results indicate that cardiac sympathetic neuronal function is relatively preserved at the compensated, hypertrophic stage of DS rats but deteriorates in association with ß-receptor downregulation at the failing stage. The cardiac neuronal dysfunction occurs heterogeneously. A combination of scintigraphic portrayal of ß-receptors with MIBG should provide valuable information regarding sympathetic nerve signaling in living hearts.

Key Words: heart failure • hypertrophy • receptors, adrenergic, beta • nervous system, autonomic • radioisotopes

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