Alexander B T, Cockrell K L, Rinewalt A N, Herrington J N, Granger J P
Department of Physiology and Biophysics, Center for Excellence in Cardiovascular-Renal Research, University of Mississippi Medical Center, Jackson, Mississippi 39216, USA.
Am J Physiol Regul Integr Comp Physiol. 2001 May;280(5):R1388-92. doi: 10.1152/ajpregu.2001.280.5.R1388.
The purpose of this study was to determine the role of endothelin in mediating the renal hemodynamic and arterial pressure changes observed during chronic ANG II-induced hypertension. ANG II (50 ng x kg(-1) x min(-1)) was chronically infused into the jugular vein by miniosmotic pump for 2 wk in male Sprague-Dawley rats with and without endothelin type A (ET(A))-receptor antagonist ABT-627 (5 mg x kg(-1) x day(-1)) pretreatment. Arterial pressure increased in ANG II rats compared with control rats (149 +/- 5 vs. 121 +/- 6 mmHg, P < 0.05, respectively). Renal expression of preproendothelin mRNA was increased by approximately 50% in both the medulla and cortex of ANG II rats. The hypertensive effect of ANG II was completely abolished in rats pretreated with the ET(A)-receptor antagonist (114 +/- 5 mmHg, P < 0.05). Glomerular filtration rate was decreased by 33% in ANG II rats, and this response was attenuated in rats pretreated with ET(A)-receptor antagonist. These data indicate that activation of the renal endothelin system by ANG II may play an important role in mediating chronic renal and hypertensive actions of ANG II.
本研究的目的是确定内皮素在介导慢性血管紧张素II（ANG II）诱导的高血压过程中所观察到的肾血流动力学和动脉压变化中的作用。通过微量渗透泵将ANG II（50 ng·kg⁻¹·min⁻¹）长期输注到雄性Sprague-Dawley大鼠的颈静脉中，持续2周，这些大鼠分为两组，一组预先用A型内皮素（ET(A)）受体拮抗剂ABT-627（5 mg·kg⁻¹·day⁻¹）进行预处理，另一组未预处理。与对照大鼠相比，ANG II大鼠的动脉压升高（分别为149±5 vs. 121±6 mmHg，P<0.05）。在ANG II大鼠的髓质和皮层中，前内皮素原mRNA的肾表达均增加了约50%。在用ET(A)受体拮抗剂预处理的大鼠中，ANG II的高血压作用完全被消除（114±5 mmHg，P<0.05）。ANG II大鼠的肾小球滤过率降低了33%，而在用ET(A)受体拮抗剂预处理的大鼠中，这种反应减弱。这些数据表明，ANG II激活肾内皮素系统可能在介导ANG II的慢性肾脏和高血压作用中起重要作用。
