Analysis of alpha(1)-adrenoceptor subtypes in rabbit aorta and arteries: regional difference and co-existence

This study was done to determine the alpha(1)-adrenoceptor subtypes and to characterize the functional role of a(1D)-adrenoceptors in the following ra bbit arteries. thoracic and abdominal aorta, mesenteric, renal and iliac ar teries. In all arteries, selective a(1D)-adrenoceptor antagonist BMY 7378 ( 8-(2-(4-(2-methoxyphenyl)-1-piperazinyl)ethyl)-8-azaspirol(4,5) decane-7,9- dione dihydrochloride) dose dependently shifted the concentration-response curves for norepinephrine to the right. Schild plots of the results obtaine d from the inhibition by BMY 7378 for norepinephrine yielded a straight lin e with a slope of unity in thoracic (pA(2) 6.54 +/- 0.02) and abdominal (pA (2) 6.73 +/- 0.03) aorta. Slopes of Schild plots obtained from the inhibiti on by BMY 7378 for norepinephrine were significantly different from unity i n mesenteric, renal and iliac arteries. Slopes of Schild plots for Bhn 7378 were not different from unity in chloroethylclonidine-treated thoracic (pA (2) 6.49 +/- 0.14) and abdominal (pA(2) 6.61 +/- 0.11) aorta. Slopes of Sch ild plots for BMY 7378 were significantly different from unity in chloroeth ylclonidine-treated mesenteric, renal and iliac arteries. On the other hand , in Ca2+-free physiological saline solution (Ca2+-free PSS) slopes obtaine d from Schild plots for BMY 7378 were not different from unity in thoracic (pA(2) 6.41 +/- 0.09) and abdominal (pA(2) 6.28 +/- 0.07) aorta and mesente ric (pA(2) 6.55 +/- 0.06), renal (pA(2) 6.14 +/- 0.10) and iliac (pA(2) 6.6 4 +/- 0.13) arteries. BMY 7378 inhibited [H-3]prazosin binding to thoracic (pK(i) 6.44 +/- 0.08) and abdominal (pK(i) 6.59 +/- 0.02) aorta with low po tency, and mesenteric (pK(i High) 8.66 +/- 0.28, pK(i Low) 6.34 +/- 0.14), renal (pK(i High) 8.71 +/- 0.33, pK(i Low) 6.45 +/- 0.03) and iliac artery (pK(i High) 8.60 +/- 0.24, pK(i Low) 6.56 +/- 0.13). These results suggest that alpha(1D)-adrenoceptors play a significant role for contractile respon ses in renal and iliac artery, but play virtually no role in thoracic and a bdominal aorta and that an alpha(1)-adrenoceptor subtype, which is pharmaco logically distinguishable from the alpha(1A)-, alpha(1B)- and alpha(1D)-adr enoceptor subtype, may co-exist in mesenteric artery. (C) 1999 Elsevier Sci ence B.V. All rights reserved.