Fadda G Z, Massry S G, el-Refai M, Campese V M
Division of Nephrology, University of Southern California School of Medicine, Los Angeles.
Kidney Int. 1988 Oct;34(4):463-6. doi: 10.1038/ki.1988.203.
In previous studies we have shown that patients or rats with chronic renal failure display reduced blood pressure response to norepinephrine (NE). This abnormality is related to the high levels of parathyroid hormone (PTH) which stimulates vasodilator prostaglandin production. To determine whether chronic renal failure (CRF) also affects pressor response to NE through changes in the properties of alpha 1 adrenoceptors, we have measured plasma NE and the number of binding sited (Bmax) and the KD of these receptors in isolated mesenteric arteries of normal CRF rats and of CRF rats previously parathyroidectomized (PTX). Plasma NE was greater (P less than 0.01) in CRF than in control (67 +/- 14 vs. 32 +/- 3.1 ng/dl), but it was not different from CRF-PTX rats. The Bmax of alpha 1 adrenoceptors was lower (P less than 0.05) in CRF than control (80 +/- 10 vs. 173 +/- 29 fmol/mg protein), but it was similar in CRF and CRF-PTX rats. The KD was not significantly different among the three groups of rats studied. The data show that the number of alpha 1 adrenoceptors is reduced in CRF and this is not related to excess PTH. This abnormality may contribute to the reduced pressor response to NE in CRF. The effect of PTH, on the vascular response to NE is not related to changes in plasma levels of NE or in binding sites for NE.
在先前的研究中,我们已经表明,慢性肾功能衰竭患者或大鼠对去甲肾上腺素(NE)的血压反应降低。这种异常与甲状旁腺激素(PTH)水平升高有关,PTH会刺激血管舒张性前列腺素的产生。为了确定慢性肾功能衰竭(CRF)是否也通过α1肾上腺素能受体特性的改变影响对NE的升压反应,我们测量了正常CRF大鼠、先前已做甲状旁腺切除术(PTX)的CRF大鼠的离体肠系膜动脉中的血浆NE、结合位点数量(Bmax)以及这些受体的解离常数(KD)。CRF大鼠的血浆NE高于对照组(P<0.01)(67±14对32±3.1 ng/dl),但与CRF-PTX大鼠无差异。CRF大鼠α1肾上腺素能受体的Bmax低于对照组(P<0.05)(80±10对173±29 fmol/mg蛋白),但CRF大鼠和CRF-PTX大鼠相似。三组研究大鼠的KD无显著差异。数据表明,CRF中α1肾上腺素能受体数量减少,且这与PTH过量无关。这种异常可能导致CRF中对NE的升压反应降低。PTH对血管对NE反应的影响与血浆NE水平或NE结合位点的变化无关。