Lucchesi P A, DeRoux N, Berk B C
Department of Medicine, Emory University School of Medicine, Atlanta, Ga.
Hypertension. 1994 Dec;24(6):734-8. doi: 10.1161/01.hyp.24.6.734.
The Na(+)-H+ exchanger has important modulatory effects on vascular smooth muscle cell proliferation and contractility. Increased Na(+)-H+ exchange activity is a general property of many tissues, including mesenteric artery and cultured vascular smooth muscle cells, in the spontaneously hypertensive rat (SHR). In the present work, we investigated whether alterations in the steady-state levels of specific Na(+)-H+ exchanger mRNA isoforms (NHE-1 through NHE-4) are associated with the observed increases in exchanger activity. Poly(A+) mRNA prepared from 12-week-old hypertensive SHR and normotensive Wistar-Kyoto (WKY) aorta, kidney, and intestine was hybridized to cDNAs specific for each NHE isoform. By Northern blot analysis, NHE-1 was detected in all tissues as well as cultured vascular smooth muscle cells and was not regulated differently in SHR compared with WKY tissues. There was no expression of NHE-2, NHE-3, or NHE-4 in SHR and WKY aortas or in cultured vascular smooth muscle cells from SHR and WKY aortas. Stimulation of NHE-1 mRNA expression by growth factors was similar in cultured SHR and WKY vascular smooth muscle cells. We conclude that the previously observed increase in exchanger activity in blood vessels and cultured vascular smooth muscle cells of the SHR is not caused by induction of the NHE-2, NHE-3, and NHE-4 isoforms or by alterations in steady-state NHE-1 mRNA expression. These findings suggest that posttranslational regulation of the Na(+)-H+ exchanger is responsible for increased activity in the SHR.
钠氢交换体对血管平滑肌细胞的增殖和收缩性具有重要的调节作用。钠氢交换活性增加是许多组织的共同特性，包括自发性高血压大鼠（SHR）的肠系膜动脉和培养的血管平滑肌细胞。在本研究中，我们调查了特定钠氢交换体mRNA亚型（NHE-1至NHE-4）的稳态水平变化是否与观察到的交换体活性增加有关。从12周龄的高血压SHR和正常血压的Wistar-Kyoto（WKY）大鼠的主动脉、肾脏和肠道制备的多聚腺苷酸（Poly(A+)）mRNA与每种NHE亚型特异性的cDNA进行杂交。通过Northern印迹分析，在所有组织以及培养的血管平滑肌细胞中均检测到NHE-1，并且与WKY组织相比，SHR中NHE-1的调节没有差异。在SHR和WKY大鼠的主动脉中，以及从SHR和WKY大鼠主动脉培养的血管平滑肌细胞中，均未检测到NHE-2、NHE-3或NHE-4的表达。生长因子对培养的SHR和WKY血管平滑肌细胞中NHE-1 mRNA表达的刺激作用相似。我们得出结论，先前观察到的SHR血管和培养的血管平滑肌细胞中交换体活性增加，不是由NHE-2、NHE-3和NHE-4亚型的诱导或NHE-1 mRNA稳态表达的改变引起的。这些发现表明，钠氢交换体的翻译后调节是SHR中活性增加的原因。
