AIM To observe whether acute stimulation of BRL 37344, a β_3-adrenergic receptor (β_3-AR) agonist, has the same effects of exacerbating hemodynamics and increasing in β_3-AR expression on rats with failing heart as chronic administration. METHODS Rats 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.RESULTS Compared with Iso group, heart rate, left ventricular end systolic pressure and +dp/dt_ max 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 β_1-, β_2- and β_3-AR mRNA displayed no significant change in BRL group; the level of β_1-AR mRNA was lower and the level of β_3-AR mRNA was higher in Iso group.
In Iso+BRL group, much more lower β_1-AR mRNA level and much higher β_3-AR mRNA level were shown on d 2 and d 7 than Iso group.CONCLUSION Acute administration of β_3-AR agonist has a shorter improved hemodynamics. But it caused the same result as chronic administration in reduction of β_1-AR mRNA and increment of β_3-AR
Received date:2005-04-04 Accepted date:2005-12-02 Foundation item:The project supported by Heilongjiang Province Education Bureau(10551171); and by Heilongjiang Province Health Bureau (2002-036) Biography:KONG Yi-Hui (1967-), female, native of Anqing, Anhui Province, associate professor, MD, main research field is cardiovascular pharmacology. ~*Corresponding author. E-mail: kongyihui@yahoo.com Tel: (0451)53643849-5462 mRNA in failure hearts, which may aggravate the cardiac functions.