(C ) 33 2 SCIENCE IN CHINA ( Series C ) 2003 4 α 1A - žœ x * q o ** ( q, g, 100083) u e, e e,, ƒα 1 - žœ (α 1 -AR) x, ¹α 1 -AR x u. : α 1 -AR (prazosin 13.5A3.6 vs 15.1A4.3, n = 11) α 1A -AR (5-methyl-urapidil 2.4A0.9 vs 3.7A2.3, n = 12; RS-17053 3.2A1.6 vs 4.4A3.3, n = 12) žœ  Ž Ž x (dose ratio, Dr), α 1D -AR (BMY 7378 1.9A 0.9 vs 2.2A0.8, n =8) žœ ; (RS-17053 3.4A0.6 vs 4.3A0.9, n = 5; BMY 7378 1.7A0.5 vs 1.7A0.5, n =8)x z. žœ  xα 1 -AR  xα 1 -AR ƒ, α 1A -AR. ¼ α 1 - žœ x, x, ¹  x. Âx uα 1 - žœ (α 1 -adrenergic receptor, α 1 -AR). xα 1 -AR, º [1~8]. α 1 -AR ( 5-methyl-urapidil, chloroethylclonidine, SZL-49, BMY7378 Š) x, x, u y x x, x u. x α 1 -AR α 1A -AR [9], u e, e e, ƒα 1 -AR (5-methyl-urapidil, RS17053, BMY7378 Š) x, ¹α 1 -AR x u, uz x (spontaneously hypertensive rats, SHR) xα 1 -AR, SHR x. 1 1.1 Wistar, 250~350 g, u. SHRu 2002-08-05, 2002-10-28 * jƒ ( : 30070872) g ( : G2000056906)À z **, E-mail: zhangyy@bjmu.edu.cn
134 ƒ (C ) 33, 15~16, 230~300 g. 1 22j, 12h/12h / n.. 1.2 e u 1 mg/kg, ž., u α 1 -AR,, Œ 1000 u. e,, ( ½ ), e nå, e 2 ml/min. nå x e,, u MacLab º º. 1.3 Œƒ Žx α 1 -AR, 0.1 nmol/kg (1 ml/kg), u (1~2 min), Œƒ, ƒ Œƒ Ž, j tpy. 1.4 žœ Žx Œƒ Ž α 1 -AR x u, 5-methyl-urapidil (0.1 µmol/kg), RS-17053 (0.5 µmol/kg, Wiatar ; 1µmol/kg, SHR) BMY 7378 (1 µmol/kg) Š, j tpy 0.1 ml/100 g. 10 min,, u Œƒ žœ(phenylephrine, PE; 3min, e, ), PE Âx e x Ž(dose-response curve, DRC). 1.5 žœ ¾ Sigma ; 5-methyl-urapidil, BMY 7378 (8-[2-[4-(2-methoxyphenyl)- 1-piperazinyl]ethyl]-8-azaspirol[4.5]decane-7,9-dione), spiperone (8-[3-(p-Fluorobenzoyl)propyl]- 1-phenyl-1,3,8-triazaspiro-[4,5]decan-4-one)¾ Research Biochemicals Inc. (Natick, ); RS- 17053 (N-[2-(2-cyclopropylmethoxy-phenoxy) ethyl]-5-chloro-α, α-dimethyl-1h-indole-3-ethanamine hydrochloride Roche Bioscience( ) Á; ¼. 1.6 ¹ p (XAs). ¹ u ANOVA, t, P <0.05 ¹. 2 2.1 α 1 -AR x, BMY 7378, RS-17053, WB 4101, 5-methyl-urapidil spiperone Á. x 100%, u, x 65%, 52%, 67%, 64%, 68% 57% ( P <0.01). 0.1 µmol/kg, BMY7378 1 µmol/kg, RS-17053 1 µmol/kg, WB 4101 1 µmol/kg, 5-methyl-urapidil 0.1 µmol/kg spiperone 1 µmol/kg, x 64%, 47%, 55%, 64%, 61% 57% ( P <0.01), u 30 min
2 qš: α 1A- žœ x 135 ( 1). 2.2 α 1 -AR PE  e x α 1 -AR α 1A -AR 5-methyl-urapidil, RS-17053 α 1D -AR BMY 7378 Š PE e x ED 50, o Ž, j x, o ƒ : e ED 50 x ( 1, 2). α 1 -AR PE PE e DRC x ED 50 (dose ratio, Dr) 13.5A3.6 15.1A4.3 (n = 11); 5-methyl-urapidil x ED 50 x Dr 2.4A0.9 3.7A2.3 (n = 12); RS-17053 3.2A1.6 4.4 A3.3 (n = 10); BMY 7378 Âx ED 50 x Dr 1.9A0.9 2.2A0.8 (n =8).5-methyl- 1 α 1 -AR PE  Wistar (MABP) e (FAPP) x ED 50/µgBkg 1 Dr /mmhg MABP FAPP MABP FAPP MABP FAPP j (n = 10) 163A54 3.9A1.3 101A13 138A41 prazosin (n =11) 2208A587** 58.9A16.8** 13.5A3.6 15.1A4.3 a) 105A15 b) 140A30 b) 5-methyl-urapidil (n = 12) 393A148** 14.4A9.0** 2.4A0.9 3.7A2.3 a) 91A17 b) 138A35 b) RS-17053 (n = 12) 528A263** 17.1A12.8** 3.2A1.6 4.4A3.3 a) 103A20 b) 145A24 b) BMY 7378 (n =8) 307A141** 8.5A3.1** 1.9A0.9 2.2A0.8 a) 110A11 b) 150A23 b) 1 ** P < 0.01, j ; a)p > 0.05, MABP ; b)p > 0.05, j α 1 -AR x * P < 0.05 (BMY 7378 10 nmol/kg), j ; ** P < 0.01(prazosin, 5-methyl-urapidil, WB 4101 0.1 µmol/kg 1, 10 µmol/kg), j. Con, BMY, RS, WB, Spi, 5MU Pra tpy, BMY 7378, RS-17053, WB 4101, spiperone, 5-methyl-urapidil. n =4~5 2 α 1A -AR RS-17053 PE  Wistar e ((a)) ((b)) x j, n = 10; RS-17053 1 µmol/kg, n =12
136 ƒ (C ) 33 urapidil, BMY 7378 RS-17053 PE Âx e x. 2.3 α 1 -AR PE  SHR e x SHR RS-17053 Âx PE PE e ED 50 x Dr 3.4A0.6 4.3A0.9 (n = 5), BMY 7378 Âx ED 50 x Dr 1.7A0.5 1.7A0.5 (n =8),. RS-17053 BMY 7378 PE Âx e x ( 2, 3). 2 α 1 -AR PE  e x ED 50/µgBkg 1 Dr /mmhg MABP FAPP MABP FAPP MABP FAPP j (n = 6) 158A100 2.9A1.0 121A22 144A24 RS-17053 (n =5) 533A92** 12.3A2.5** 3.4A0.6 4.3A0.9 a) 120A22 b) 135A31 b) BMY 7378 (n =8) 264A82* 5.0A1.4** 1.7A0.5 1.7A0.5 a) 143A25 b) 141A28 b) * P < 0.05, j ; ** P < 0.01, j ; a)p > 0.05, MABP ; b)p > 0.05, j 3 ¹º 3 α 1A -AR RS-17053 PE  SHR e ((a)) ((b)) x j, n =6; RS-17053 1 µmol/kg, n =5 jz, α 1 -AR α 1A -, α 1B - α 1D -AR 3 ƒ [10], 3 ƒ α 1 -AR š, α 1 -AR d u žœ Âx xα 1 -AR z, [11,12] [12] Ÿ [12~14] x α 1 -AR α 1D -, [13,14] α 1A -AR, [15] [16] α 1A - α 1B -AR. ƒα 1 -AR x o, ¼ x  u, w u x w x, ¹x º. x xα 1 -AR x. ¹ : (r) x ( 5-methyl-urapidil, SZL-49, BMY7378 Š) x, PE x [1~8] Š, x z x, SZL-49 α 1A -AR, p α 1B -AR u [17,18]. ƒ Œx, ƒ Â
2 qš: α 1A- žœ x 137, { x, x u.,, 5-methyl-urapidil, RS-17053, WB 4101, spiperone BMY 7378 Š, g, x o x. (s) α 1 -AR x, u. BMY7378 uxα 1D -AR, x» BMY7378 Âx α 1D -AR, u d 5- Âx [19]. (t) ¹ x, Cavalli Š [5] uα 1B -AR, o PE Âx j, α 1B -AR x α 1 -AR. x, x, AR ( x u)š Œ, x, Âx Œ x, ¹ ½ x [20]. ƒα 1 -AR  u? u x»¹, x» xα 1 -AR α 1A -AR, j, ƒ PE  x, u ƒα 1 -AR. u ux ux, e, α 1 -AR d, ¹, e PE x α 1A -AR. u u e, α 1 -AR, x x. x, x Œ, ( Œƒ Ž)  PE Ž ŠŠ, 5-methyl-urapidil 0.1 µmol/kg, RS-17053 0.5 µmol/kg, BMY 7378 1 µmol/kg, SHR RS-17053 1 µmol/kg BMY 7378 1 µmol/kg ( 1 2)., α 1 -AR PE Âx e x, PE  x uα 1 -AR. 5-methyl-urapidil RS-17053 α 1A -AR, PE  Ž Žx, BMY 7378 α 1D -AR, PE,, PE x xα 1 -AR  xα 1 -AR ƒ, α 1A -AR. SHR, x z, α 1A -AR RS-17053  PE x Ž Ž. α 1D -AR BMY 7378 x PE,, SHR PE x xα 1 -AR α 1A -AR., [9] Ÿ [21] [22,23] x, α 1A -AR x AR, SHR x AR α 1D -AR, ¹α 1A -AR x AR [24]., pu x AR α 1A -AR,».
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