Enhanced renal expression of preproendothelin mRNA during chronic angiotensin II hypertension

The purpose of this study was to determine the role of endothelin in mediat ing the renal hemodynamic and arterial pressure changes observed during chr onic ANG II-induced hypertension. ANG II (50 ng.kg(-1).min(-1)) was chronic ally infused into the jugular vein by miniosmotic pump for 2 wk in male Spr ague-Dawley rats with and without endothelin type A (ETA)-receptor antagoni st ABT-627 (5 mg.kg(-1).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 increa sed by <similar to>50% in both the medulla and cortex of ANG II rats. The h ypertensive effect of ANG II was completely abolished in rats pretreated wi th the ETA-receptor antagonist (114 +/- 5 mmHg, P, 0.05). Glomerular filtra tion rate was decreased by 33% in ANG II rats, and this response was attenu ated in rats pretreated with ETA-receptor antagonist. These data indicate t hat activation of the renal endothelin system by ANG II may play an importa nt role in mediating chronic renal and hypertensive actions of ANG II.