[Effects of NG-nitro-L-arginine methyl ester on hemodynamics and beta-adrenoreceptors mRNA in rats with heart failure after beta3-adrenergic receptors agonist injection].

Abstract

OBJECTIVE:

To evaluate the effects of different doses of N(G)-nitro-L-arginine methyl ester (L-NAME) on hemodynamics, cyclic guanosine monophosphate (cGMP) production and the level of beta-adrenergic receptors (beta-ARs) mRNA in a heart failure rat model after BRL-37344 (beta(3)-ARs agonist) injection. Meanwhile, to investigate the influence of beta(3)-ARs and L-NAME on signal transduction in failing heart.

METHODS:

The rats were randomly divided into six groups, control group (group I), Iso (isoproterenol) group (group II), Iso + BRL group (group III), Iso + BRL + low dose of L-NAME group (5 mg/kg, group IV), Iso + BRL + moderate dose of L-NAME group (50 mg/kg, group V), Iso + BRL + high dose of L-NAME group (100 mg/kg, group VI). The hemodynamics [left ventricular end systolic pressure (LVESP), +/- dp/dt, left ventricular end diastolic pressure (LVEDP)], cardiac cGMP and the levels of beta(1)-, beta(2)-, and beta(3)-ARs mRNA were measured.

RESULTS:

(1) LVESP, +/- dp/dt values in group II were significantly lower, and LVEDP was significantly higher than that in group I (except -dp/dt P < 0.05, the rest were P < 0.01). Comparing with group II, group III had lower -dp/dt value and LVESP, higher LVEDP (P < 0.05). The level of +dp/dt had a trend to be lower but lacked statistical significance between two groups. The value of +/- dp/dt got higher and LVEDP got lower along with higher dose of L-NAME, but a large dose of L-NAME had more deteriorated cardiac functions. (2) The cardiac cGMP in group I, II and III had a higher tendency (P < 0.01). The tendency of cardiac cGMP in group IV, V and VI was inversed with the dose of L-NAME. After a large dose of L-NAME was applied, cGMP returned to the same level as Group I. (3) Among groups I, II and III, the level of beta(1)-AR mRNA was the highest in group I and the lowest in group III (P < 0.01). The levels of beta(2)-AR mRNA were also tended to be lower among three groups but with no significance. While the level of beta(3)-AR mRNA was the highest in group III. The levels of beta-AR mRNA were all the same in group VI, V and VI.

CONCLUSIONS:

The negative inotropic effect of beta(3)-ARs stimulation was mediated by activation of the NOS pathway. L-NAME blocked beta(3)-ARs agonist negative chronotropic effect on failing heart partly and improved hemodynamics, but a large dose of L-NAME had more deteriorated cardiac functions.

• Authors: Wei-min Li, Yi-hui Kong, Jing-yi Xue, Ying Tian
• Journal: Zhonghua xin xue guan bing za zhi (Zhonghua Xin Xue Guan Bing Za Zhi) Vol. 33 Issue 6 Pg. 509-12 (Jun 2005) ISSN: 0253-3758 [Print] China
• PMID: 16053782 (Publication Type: English Abstract, Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Adrenergic Agonists
• RNA, Messenger
• Receptors, Adrenergic, beta-3
• Cyclic GMP
• NG-Nitroarginine Methyl Ester

Topics

• Adrenergic Agonists (therapeutic use)
• Animals
• Cyclic GMP (metabolism)
• Heart Failure (drug therapy, metabolism, physiopathology)
• Male
• NG-Nitroarginine Methyl Ester (administration & dosage, pharmacology)
• RNA, Messenger (metabolism)
• Rats
• Rats, Wistar
• Receptors, Adrenergic, beta-3 (metabolism)