自发性高血压大鼠后肢血管床α_1肾上腺素受体亚型特征

CHARACTERIZATION OF SUBTYPE OF α1-ADRENOCEPTOR MEDIATING VASCONSTRICTION IN PERFUSED SHR HINDLIMB

研究自发性高血压大鼠（ＳＨＲ）阻力血管α１肾上腺素受体（α１－ＡＲ）亚型特征。选用大鼠后肢血管床灌流功能性实验和分别表达３种α１－ＡＲ亚型的克隆细胞上放射性配体结合实验。结果，ＳＨＲ和正常大鼠后肢血管床α１－ＡＲ介导收缩的ｐＤ２值分别为５．３６±０．０４和５．４５±０．０３（Ｐ＞０．０５），最大反应分别为２１．７±１．１和１３．６±０．５ｋＰａ（Ｐ＜０．０１）。ＲＳ－１７０５３、５－ｍｅｔｈｙｌ－ｕｒａｐｉｄｉｌ和ＢＭＹ７３７８抑制ＳＨＲ血管床对去甲肾上腺素（ＮＡ）收缩反应的ｐＡ２值分别为９．１４±０．１１、８．２６±０．２１和６．５０±０．２８，与表达α１ａ、α１ｂ或α１ｄ－ＡＲ克隆细胞上得到的ｐＫｉ值相关系数分别为０．９６、０．５７和０．５２；在正常大鼠，上述拮抗剂的ｐＡ２值分别为９．４７±０．２１、８．１０±０．２７和６．６６±０．１４，与α１ａ、α１ｂ和α１ｄ－ＡＲ相关系数分别为０．８６、０．７３和０．３４。各拮抗剂在正常大鼠和ＳＨＲ组ｐＡ２值及Ｓｃｈｉｌｄ作图得到的斜率与１之间差别均无显著性。氯乙基可乐啶５０μｍｏｌＬ－１对ＮＡ收缩血管床的反应在两组大鼠均无影响。结论，介导ＳＨＲ后肢血管床的功能性?

Objectives To characterize the subtype of α1-adrenoceptor mediated exogenous noradrenaline-induced vasopressort response in perfused SHR hindlimb. Methods The potencies (pA2 values determined by Schild plot) of α1-adrenoceptor-selective antagonists were determined by functional merasurements. The pKi values were determined by displacement of I125-BE 2254 binding from the cloned α1a, α1b and α1d-adrenoceptor, stably expressed in human embryonic kidney (HEK) 293. Results The pD2 values between SHR and Wistar rats were no different (5.36±0.04 vs 5.45(0.03,P>0.05), and the maximum vasopressor response for noradrenaline (NA) were more potency in SHR than that of Wistar rats (21.7±1.1 vs 13.6(0.5 kPa, P<0.01). The potencies (pA2 value) of α1A-adrenoceptor selective antagonists RS-17053, 5-methyl-urapidil and α1D-adrenoceptor selective antagonist BMY 7378 on inhibiting NA-induced vasopressor response in SHR determined by Schild plot were 9.14±0.11, 8.26±0.21 and 6.50±0.28, respectively, with slopes all not significantly different from unity. In compared with that of Wistar rats (9.47±0.21, 8.10±0.27 and 6.66±0.14, respectively), they were all not significant. The pA2 values of above antagonists correlated well with the binding Ki values only for α1A-adrenoceptor (r=0.96), but not for α1B-AR (r=0.57) and α1D-AR (r=0.52) in SHR. These were similar to that of Wistar rats (0.86, 0.73 and 0.34, respectively). The concentration-vasopressor response curve for noradrenaline was not significantly affected by pretreatment of 50μmol·L-1 chloroethylclonidine for 30 min in SHR vasculature. Neither did Wistar rats. Conclusions The results suggest that only α1A-adrenoceptor mediates the NA-induced vasopressor response in perfused SHR hindlimb, and the sensitity to NA is same as that of Wistar rats, but the maximum vasopressor response for NA is mor potency than that of Wistar rats.