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[易卒中型自发性高血压大鼠和Wistar-Kyoto大鼠培养的主动脉血管平滑肌细胞中心房钠尿肽受体的调节]

[Regulation of atrial natriuretic peptide receptor in cultured aortic vascular smooth muscle cells from stroke-prone spontaneously hypertensive and Wistar-Kyoto rats].

作者信息

Liao Y B, Zhang Q, Ding J F

机构信息

Cardiovascular Institute, Chinese Academy of Medical Sciences, Beijing.

出版信息

Sheng Li Xue Bao. 1991 Aug;43(4):368-75.

PMID:1661442
Abstract

The specific binding sites for atrial natriuretic peptide (ANP) were present in cultured vascular smooth muscle cells (VSMC) from stroke-prone spontaneously hypertensive (SHRsp) and Wistar-Kyoto(WKY) rats with a Bmax of 3.65 +/- 0.13 and 1.89 +/- 0.09 pmol/mg pr. and a Kd of 72.0 +/- 10.2 and 42.1 +/- 4.8 x 10(-12) mol/L, respectively. The basal levels of cGMP of the two strains showed no statistical difference. After treatment with ANP (1.67 x 10(-7) mol/L) for 5 min, the cGMP levels of VSMC were increased by 139 folds in SHRsp and 271 folds in WKY rats, i.e., cGMP levels were significantly lower in the former (P less than 0.01). Therefore, the cultured VSMC of SHRsp had higher ANP receptor density but lower affinity and responsiveness to ANP than that of WKY rats. After incubation of VSMC in the medium containing high NaCl (2-folds of normal) at 37 degrees C for 24 h, the number of ANP binding sites decreased to 34.8 +/- 8.2% in SHRsp and to 38.6 +/- 9.4% in WKY rats (P less than 0.01) with a parallel decrease of cGMP, while the affinity of ANP receptor did not change. It is suggested that the lower responsiveness of ANP receptor to ANP in SHRsp might result in a diminution of vasorelaxation to ANP and thus an increase of arterial pressure. In addition, the more down-regulation of ANP receptor by high NaCl in cultured VSMC from SHRsp implicates that it is one of the mechanisms that high dietary intake of NaCl might enhance high blood pressure.

摘要

在易中风自发性高血压大鼠(SHRsp)和Wistar-Kyoto(WKY)大鼠的培养血管平滑肌细胞(VSMC)中存在心房利钠肽(ANP)的特异性结合位点,其最大结合容量(Bmax)分别为3.65±0.13和1.89±0.09 pmol/mg蛋白,解离常数(Kd)分别为72.0±10.2和42.1±4.8×10⁻¹² mol/L。两种品系的基础环磷酸鸟苷(cGMP)水平无统计学差异。用ANP(1.67×10⁻⁷ mol/L)处理5分钟后,SHRsp大鼠VSMC的cGMP水平增加了139倍,WKY大鼠增加了271倍,即前者的cGMP水平显著较低(P<0.01)。因此,SHRsp大鼠的培养VSMC具有比WKY大鼠更高的ANP受体密度,但对ANP的亲和力和反应性较低。将VSMC在含高氯化钠(正常浓度的2倍)的培养基中于37℃孵育24小时后,SHRsp大鼠的ANP结合位点数量降至34.8±8.2%,WKY大鼠降至38.6±9.4%(P<0.01),同时cGMP平行下降,而ANP受体的亲和力未改变。提示SHRsp大鼠中ANP受体对ANP的反应性较低可能导致对ANP的血管舒张作用减弱,从而使动脉血压升高。此外,高氯化钠对SHRsp大鼠培养VSMC中ANP受体的下调作用更强,这意味着高盐饮食可能是增强高血压的机制之一。

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