Related Experiment Video
Updated: Jul 8, 2026
Ascending Aortic Constriction in Rats for Creation of Pressure Overload Cardiac Hypertrophy Model
Published on: June 29, 2014
Chronic blocking of beta 3-adrenoceptor ameliorates cardiac function in rat model of heart failure
Run-tao Gan1, Wei-min Li, Chun-hong Xiu
1Department of Cardiology, First Clinical Hospital, Harbin Medical University, Harbin 150001, China.
Insights
Blocking beta 3-adrenoceptor (AR) with SR59230A improved heart function in rats with heart failure. This treatment reduced negative inotropic effects and cardiac remodeling, offering a potential therapeutic strategy for heart failure.
Area of Science:
- Cardiology
- Pharmacology
- Molecular Biology
Background:
- Heart beta 3-adrenoceptor (AR) stimulation can negatively impact cardiac contractility.
- Beta 3-AR is upregulated and plays a crucial role in cardiac function during heart failure.
- The long-term effects of blocking beta 3-AR in heart failure remain incompletely understood.
Purpose of the Study:
- To investigate the effects of chronic beta 3-AR blockade on cardiac function in a rat model of heart failure.
- To elucidate the underlying mechanisms by which beta 3-AR antagonism influences cardiac remodeling and function.
Main Methods:
- A rat model of isoproterenol-induced heart failure was established.
- Rats received chronic treatment with the selective beta 3-AR antagonist SR59230A or a placebo for 7 weeks.
- Cardiac function, cardiac remodeling markers (e.g., HW/BW, LVW/BW, CVF), and molecular changes (beta 3-AR, eNOS, cGMP) were assessed.
Main Results:
- SR59230A treatment significantly limited increases in heart and left ventricular weight and attenuated collagen volume fraction.
- Cardiac function, indicated by ejection fraction and fractional shortening, was significantly improved in SR59230A-treated rats.
- Treatment with SR59230A reduced elevated beta 3-AR and eNOS expression and normalized cGMP levels in myocardial tissue.
Conclusions:
- Chronic blockade of beta 3-AR with SR59230A effectively ameliorates cardiac function in a rat model of heart failure.
- The therapeutic benefits involve mitigating negative inotropic effects and reducing cardiac remodeling.
- This study suggests beta 3-AR antagonism as a potential therapeutic avenue for managing heart failure.
Background:
Stimulation of the heart beta 3-adrenoceptor (AR) may result in a negative inotropic effect. Being up-regulated, beta 3-AR plays a more important role in the regulation of cardiac function during heart failure. However, the effect of chronic blocking of beta 3-AR on heart failure has not been fully elucidated. In this study, we used a selective beta 3-AR antagonist SR59230A to treat a well defined heart failure rat model chronically, then evaluated its effect on cardiac function and investigated the mechanism.
Methods:
Male Wistar rats were chosen randomly as controls (n = 8). Isoproterenol induced heart failure rats were randomly divided into ISO group (n = 10) and SR group (n = 10). The ISO group received intraperitoneal injection of 1 ml saline twice a day; the SR group received intraperitoneal injection of SR59230A 85 nmol in 1 ml saline twice a day; and the control group received no treatment. The treatment was started 24 hours after the last isoproterenol injection and continued for 7 weeks. Then we measured the following indexes: the ratio of heart weight to body weight (HW/BW) and the ratio of left ventricular weight to body weight (LVW/BW), collagen volume fraction (CVF), left ventricular end diastolic dimension (LVEDd), left ventricular end systolic dimension (LVESd), ejection fraction (EF), fractional shortening (FS) and the ratio of E wave to A wave (E/A), the mRNA and protein expression of beta 3-AR and eNOS, and cGMP level in the heart.
Results:
The ratios HW/BW and LVW/BW were significantly increased in the ISO group compared with the control group (P < 0.01), but they were limited in the SR group (P < 0.05 compared with the ISO group). CVF increased in the ISO group and the SR group (P < 0.01), but it was significantly attenuated in the SR group (P < 0.01). LVEDd, LVESd and E/A ratio were significantly increased in the ISO group compared with the control group (P < 0.01), while EF and FS were significantly decreased (P < 0.01). Compared with the ISO group, the SR group showed that LVEDd, LVESd and E/A ratio were significantly decreased (P < 0.01), whereas EF and FS were significantly increased (P < 0.01). beta(3)-AR and eNOS mRNA and protein in the ISO group were significantly increased when compared with the control group (P < 0.01). These increases were all attenuated in the SR group compared with the ISO group (P < 0.01). The level of cGMP in myocardial tissue was significantly increased in the ISO group compared with the control group (P < 0.01), whereas SR59230A treatment normalized this increment (P < 0.01).
Conclusions:
Chronic blocking of beta 3-AR could ameliorate cardiac function in heart failure rats and its mechanism involves inhibition of the negative inotropic effect and attenuation of cardiac remodeling.
Related Concept Videos
01:22Heart Failure Drugs: β-Blockers
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:31Adrenergic Antagonists: ɑ and β-Receptor Blockers
01:27Adrenergic Antagonists: Pharmacological Actions of β-Receptor Blockers
01:17Antihypertensive Drugs: Action of β1 Blockers
01:22Heart Failure Drugs: Diuretics