Expression And Functional Study Of β₃ Adrenoceptors On Rat Thoracic Aorta Smooth Muscle

Objective:To observe the effect of β₃ adrenoceptors（β₃-AR） activation on rat thoracic aortasmooth muscle contractility and the possible mechanism related. Methods:1. The endothelium-removed thoracic aorta was pre-contracted with 30 m M KCl physiological saline solution（PSS）. Then the tension of the thoracic aorta was recorded in presence of BRL37344（BRL） to determine the action of β₃-AR.. 2. The tension of the thoracic aorta was also recorded in presence of Propranolol（Pra）, SR59230A（SR）, L-NNA, H-89 and Iberiotoxin（IBTX） respectively to reveal the underling mechanism of β₃-AR activation on rat vascular smooth muscle. 3. Chronic heart failure（CHF） model was built via ligation of the rat left anterior coronary artery.The response of CHF thoracic aorta to BRL was observed. 4. Immunochemistry was adopted to confirm the existence and the distribution of β₃-AR in thoracic aorta of normal and CHF rats. Results:1. BRL produced the concentration-dependent relaxation in isolated thoracic aorta with or without endothelium.When BRL of the maximal concentration was used singly,the relaxation percentage was（10.59±0.79）%. 2. Pra did not block the effect of BRL on the thoracic aorta. The relaxation actions of BRL could be antagonized by pre-incubating the thoracic aorta with SR. 3. L-NNA（NOS inhibitor） and H-89（PKA inhibitor） reversed the relaxation effect of BRL on vascular smooth muscle. 4. The effect of BRL was reversed after application of Ibriotoxin（IBTX）, a large conductance calcium dependent potassium channel blocker. 5. The effect of BRL on thoracic aorta augmented in CHF rats with the relaxation percentage of（15.93±0.90）%. 6. β₃-AR was expressed in both endothelial and smooth muscle layer in thoracic aorta sections of rats.The expression of β₃-AR was up-regulated in CHF rats. Conclusions:The results confirmed that β₃-AR was expressed in smooth muscle of rat thoracic aorta and mediated the relaxation of the thoracic aorta. The relaxation action of β₃-AR on smooth muscle of rat thoracic aorta was related to activation of NOS and PKA signaling pathway. Large conductance Ca2+-K+ channels was involved in the relaxation action of β₃-AR activation on rat thoracic aorta smooth muscle.