Heterogenous activity of BRL 35135, a beta 3-adrenoceptor agonist, in thermogenesis and increased blood flow in brown adipose tissue in anaesthetized rats.

1. The effects of BRL 35135, a beta 3-adrenergic agonist, on body temperature and regional blood flow in brown adipose tissue (BAT) were simultaneously recorded in anaesthetized rats and compared to isoproterenol. 2. BRL 35135 at doses of 0.1 and 1 micrograms/kg (i.v.) induced dose-dependent increases in BAT temperature with minimal effects on systemic diastolic blood pressure (DBP), heart rate (HR) and BAT blood flow. 3. The thermogenic effect of BRL 35135 at a dose of 10 micrograms/kg (i.v.) was smaller than that at a dose of 1 microgram/kg, and was accompanied by a marked increase in BAT blood flow. 4. Isoproterenol at doses of 0.01-1 microgram/kg (i.v.) dose-dependently increased HR and BAT blood flow and decreased DBP. It did not affect BAT temperature. 5. These findings indicate that unlike isoproterenol, BRL 35135, at the lower doses, selectively causes thermogenesis in BAT which was detectable as changes in BAT temperature, and that the vasodilator effect in BAT is not as sensitive as the thermogenic effect of beta 3-adrenergic agonists.