CGP 12177A-induced relaxation of vascular smooth muscle has been attributed to agonist activity at β₃- and/or atypical β- adrenoceptors (AR). We have previously shown that isoprenaline-induced relaxation of rat femoral resistance arteries involves only β₁-AR (Brahmadevara et al., 2003a). This study aimed to characterise the relaxation to CGP 12177A in rat femoral resistance arteries.

Male Wistar rats (200-250 g) were stunned and killed by cervical dislocation. Third order femoral small arteries (c. 230 μm) were dissected out and mounted on a small vessel wire myograph for isometric recording in physiological saline solutiongassed with 95/5% O₂/CO₂ at 37°C. Arteries were pre-constricted with phenylephrine (PE, 1 μM) or U46619 (30 nM) before performing cumulative concentration-response curves (CRCs) to agonists. In antagonist studies, tissues were incubated with antagonist for 30 min before performing CRCs. Values are mean±s.e.mean.

CGP 12177A produced concentration-dependent, full relaxation of PE-constricted rings (pEC₅₀, 4.44±0.02, n=6). CGP 12177A (200 μM, n=7) failed to produce relaxation in U46619-constricted vessels although isoprenaline produced relaxation with similar potency as in PE-constricted vessels (pEC₅₀: PE-constricted, 7.19±0.02; U46619-constricted, 7.06±0.02, n=7). Relaxations to CGP 12177A were unaffected by propanolol (1 μM), S R 59230A (1 μM) or by CGP 20712A (10 μM). β-adrenoceptor antagonists also produced relaxation of PE -constricted rings (pEC₅₀ : SR 59230A, 5.80±0.12, n=5; CGP 20712A, 3.96±0.05, n=7; bupranolol, 5.57±0.08, n=5; cyanopindolol, 6.88±0.11, n=6; ICI 118551, 5.00±0.24, n=6; propranolol, 5.60±0.13, n=6). Pre-incubation with CGP 12177A (200 μM) shifted the PE CRC to the right (pEC₅₀: PE control, 5.92±0.05, n=5; CGP 12177A 5.06±0.04, n=5).

In conclusion, CGP 12177A-induced relaxation of rat femoral resistance arteries is not due to activation of β₃- or atypical β- AR . The concentrations of CGP 12177A and other β-adrenoceptor antagonists producing relaxation are consistent with the ₁-AR affinity of these compounds (Brahmadevara et al., 2003b).

Brahmadevara, N., Hillier, C., Shaw, A.M., & MacDonald, A. (2003a) Br. J. Pharmacol., 138, 154P
Brahmadevara, N., Shaw, A.M., & MacDonald A. (2003b) pA 2 ., 3, 4P