Effects of acute injection of BRL 37344 on hemodynamics and β-adrenoreceptors expression in myocardium of rats with heart failure / 中国药理学与毒理学杂志

ABSTRACT

AIM To observe whether acute stimulation of BRL 37344, a β3-adrenergic receptor (β3-AR) agonist, has the same effects of exacerbating hemodynamics and increasing in β3-AR expression on rats with failing heart as chronic administration. METHODSRats received two doses of isoprenaline (Iso, 340 mg·kg-1, sc, with a 24-h interval) to prepare heart failure model. After 8 weeks, rats were given iv BRL 37344 0.4 nmol·kg-1·min-1 for 10 min. Hemodynamics were measured at 0, 10, 30 min, 1, 2, 3 h, 1, 2 and 7 d after BRL 37344. Levels of β-AR mRNA in myocardium were measured at 0, 1, 2 and 7 d after BRL 37344 by reverse transcription-polymerase chain reaction. RESULTSCompared with Iso group, heart rate, left ventricular end systolic pressure and +dp/dtmax were significantly higher, and left ventricular end diastolic pressure was significantly lower during 1-3 h after BRL 37344 injection in Iso+BRL group. Then, they were restored to the same level as that prior to BRL 37344 injection. Compared with normal control, the levels of β1-, β2- and β3-AR mRNA displayed no significant change in BRL group;the level of β1-AR mRNA was lower and the level of β3-AR mRNA was higher in Iso group. In Iso+BRL group, much more lower β1-AR mRNA level and much higher β3-AR mRNA level were shown on d 2 and d 7 than Iso group. CONCLUSION Acute administration of β3-AR agonist has a shorter improved hemodynamics. But it caused the same result as chronic administration in reduction of β1-AR mRNA and increment of β3-AR mRNA in failure hearts, which may aggravate the cardiac functions.