1.1 (C ) (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 A1.6 vs 4.4A3.

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1 (C ) 33 2 SCIENCE IN CHINA ( Series C ) α 1A - žœ x * q o ** ( q, g, ) 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 A1.6 vs 4.4A3.3, n = 12) žœ Â Ž Ž x (dose ratio, Dr), α 1D -AR (BMY A 0.9 vs 2.2A0.8, n =8) žœ ; (RS A0.6 vs 4.3A0.9, n = 5; BMY A0.5 vs 1.7A0.5, n =8)x z. žœ Â xα 1 -AR Â xα 1 -AR ƒ, α 1A -AR. ¼ α 1 - žœ x, x, ¹ Â 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 Wistar, 250~350 g, u. SHRu , * jƒ ( : ) g ( : G )À z **, zhangyy@bjmu.edu.cn

2 134 ƒ (C ) 33, 15~16, 230~300 g. 1 22j, 12h/12h / n 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 (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 (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 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, BMY µmol/kg, RS µmol/kg, WB 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

3 2 qš: α 1A- žœ x 135 ( 1). 2.2 α 1 -AR PE Â e x α 1 -AR α 1A -AR 5-methyl-urapidil, RS 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) 13.5A A4.3 (n = 11); 5-methyl-urapidil x ED 50 x Dr 2.4A A2.3 (n = 12); RS A A3.3 (n = 10); BMY 7378 Âx ED 50 x Dr 1.9A A0.8 (n =8).5-methyl- 1 α 1 -AR PE Â Wistar (MABP) e (FAPP) x ED 50/µgBkg 1 Dr /mmhg MABP FAPP MABP FAPP MABP FAPP j (n = 10) 163A54 3.9A A13 138A41 prazosin (n =11) 2208A587** 58.9A16.8** 13.5A A4.3 a) 105A15 b) 140A30 b) 5-methyl-urapidil (n = 12) 393A148** 14.4A9.0** 2.4A A2.3 a) 91A17 b) 138A35 b) RS (n = 12) 528A263** 17.1A12.8** 3.2A A3.3 a) 103A20 b) 145A24 b) BMY 7378 (n =8) 307A141** 8.5A3.1** 1.9A A0.8 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 nmol/kg), j ; ** P < 0.01(prazosin, 5-methyl-urapidil, WB 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 PE Â Wistar e ((a)) ((b)) x j, n = 10; RS µmol/kg, n =12

4 136 ƒ (C ) 33 urapidil, BMY 7378 RS PE Âx e x. 2.3 α 1 -AR PE Â SHR e x SHR RS Âx PE PE e ED 50 x Dr 3.4A A0.9 (n = 5), BMY 7378 Âx ED 50 x Dr 1.7A A0.5 (n =8),. RS BMY 7378 PE Âx e x ( 2, 3). 2 α 1 -AR PE Â e x ED 50/µgBkg 1 Dr /mmhg MABP FAPP MABP FAPP MABP FAPP j (n = 6) 158A A A22 144A24 RS (n =5) 533A92** 12.3A2.5** 3.4A A0.9 a) 120A22 b) 135A31 b) BMY 7378 (n =8) 264A82* 5.0A1.4** 1.7A A0.5 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 PE Â SHR e ((a)) ((b)) x j, n =6; RS 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 Â 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

5 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 Â u? u x»¹, x» xα 1 -AR α 1A -AR, j, ƒ PE Â 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) Â PE Ž ŠŠ, 5-methyl-urapidil 0.1 µmol/kg, RS µmol/kg, BMY µmol/kg, SHR RS µmol/kg BMY µmol/kg ( 1 2)., α 1 -AR PE Âx e x, PE Â x uα 1 -AR. 5-methyl-urapidil RS α 1A -AR, PE Â Ž Žx, BMY 7378 α 1D -AR, PE,, PE x xα 1 -AR Â xα 1 -AR ƒ, α 1A -AR. SHR, x z, α 1A -AR RS Â 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,».

6 138 ƒ (C ) 33 1 Kusiak J W, Pitha J, Piasck M T. Interaction of a chemically reactive prazosin analog with α 1-adrenoceptors of rat tissues. J Pharmacol Exp Ther, 1989, 249: 70~77 2 Piascik M T, Butler B T, Kusiak J W, et al. Effect of an alkylating analog of prazosin on α 1-adrenoceptor subtype and arterial blood pressure. J Pharmacol Exp Ther, 1989, 251: 878~883 3 Piasck M T, Kusiak J W, Barron K W. α 1-adrenoceptor subtype and the regulation of peripheral hemodynamics in the conscious rat. Eur J Pharmacol, 1990, 186: 273~278 4 Kenny B A, Read A M, Naylor A M, et al. Effect of α 1-adrenoceptor antagonists on prostatic pressure and blood pressure in the anesthetized dog. Urology, 1994, 44: 52~57 5 Cavalli A, Lattion A L, Hummler E, et al. Decreased blood pressure response in mice deficient of the α 1B-adrenergic receptor. Proc Natl Acad Sci USA, 1997, 94: 11589~ Zhou L, Vargas H M. Vascular α 1D-adrenoceptors have a role in the pressure response to phenylephrine in the pithed rat. Eur J Pharmacol, 1996, 305: 173~176 7 Ibarra M, Terron J A, Lopez-Guerrero J J, et al. Evidence for an age-dependent functional expression of α 1D-adrenoceptors in the rat vasculature. Eur J Pharmacol, 1997, 322: 221~224 8 Villalobos-Molina R, Lopez-Guerrero J J, Ibarra M. Functional evidence of α 1D-adrenoceptors in the vasculature of young and adult spontaneously hypertensive rats. Br J Pharmacol, 1999, 126: 1534~ Weizhong Zhu, Youyi Zhang, Chide Han. Characterization of subtype of α 1-adrenoceptor mediating vasoconstriction in perfused rat hindlimb. Eur J Pharmacol, 1997, 329: 55~ žœ. tpƒ, 1995, 26: 103~ Buckner S A, Oheim K W, Morse P A, et al. α 1-adrenoceptor-induced contractility in rat aorta is mediated by the α 1D subtype. Eur J Pharmacol, 1996, 297: 241~ Hussain M B, Marshall I. Characterization of α 1-adrenoceptor subtypes mediating contractions to phenylephrine in rat thoracic aorta, mesenteric artery and pulmonary artery. Br J Pharmacol, 1997, 122: 849~ Piascik M T, Smith M S, Soltis E E, et al. Identification of the mrna for the novel α 1D-adrenoceptors and two other α 1-adrenoceptors in vascular smooth muscle. Mol Pharmacol, 1994, 46: 30~40 14 Han C, Li J, Minneman K P. Subtypes of α 1-adrenoceptors in rat blood vessels. Eur J Pharmacol, 1990, 190: 97~ Villalobos-Molina R, Lopez-Guerrero J J, Ibarra M. Chloroethylclonidine is a partial α 1-adrenoceptor agonist in aorta and caudal arteries of the Wistar Kyoto rat. Eur J Pharmacol, 1998, 351: 49~52 16 Macrez-Lepretre N, Kalkbrenner F, Schultz G, et al. Distinct functions of Gq and G11 proteins in coupling α 1-adrenoreceptors to Ca 2+ release and Ca 2+ entry in rat portal vein myocytes. J Biol Chem, 1997, 272: 5261~ Hoo K H, Kwan C Y, Daniel E E. Investigation of α 1-adrenoceptor subtypes in canine aorta, using alkylating agents. Can J Physiol Pharmacol, 1994, 72: 97~ Mante S, Mineman K P. The alkylating prazosin analog SZL 49 inactivates both α 1A-and α 1B-adrenoceptor. Eur J Pharmacol, 1991, 208: 113~ Villalobos-Molina R, Lopez-Guerrero J J, Ibarra M. The hypotensive effect of BMY 7378 is antagonized by a silent 5-HT(1A) receptor antagonist: comparison with 8-hydroxy-dipropylamino tetralin. Arch Med Res, 2001, 32: 389~ u ˆx žœ., 2000, 20: 207~ Zhu W Z, Zhang Y Y, Han Q D. Characterization of subtype of α 1-adrenoceptor mediating vasoconstriction in perfused rat mesenteric vascular bed. Acta Pharmaco Sinica, 1999, 20: 151~ Blue J R, Vimont R L, Clarke D E. Evidence for a noradrenergic innervation to α 1A-adrenoceptors in rat kidney. Br J Pharmacol, 1992, 107: 414~ Blue J R, Bonhaus D W, Ford A P, et al. Functional evidence equating the pharmacologically-defined α 1A-and α 1Cadrenoceptor: studies in the isolated perfused kidney of rat. Br J Pharmacol, 1995, 115: 283~ Ye J M, Colquhoun E Q. Changes in functional expression of α 1-adrenoceptors in hindlimb vascular bed of spontaneously hypertensive rats and their effects on oxygen consumption. J Pharmacol Exp Ther, 1998, 286: 599~606

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