Role of endothelins for the regulation of renal renin gene expression

Endothelin-1, -2 and -3 (ET-1, -2, -3) have suppressive effects on the renin system in different experimental in vitro models, whereas a modulation of renin secretion or renin gene expression by endothelins (ETs) in in vivo studies has not so far been found. In a recent study we observed a significant stimulation of the renin system by acute hypoxia over 6 h in rats. In the study reported here, we investigated the more chronic effects of hypoxia (10% O2 for 4 weeks) on renin gene expression and the influence of the ET system on its regulation. Renin mRNA levels decreased after 2 weeks of hypoxia to 76% of control and after 4 weeks to 49% of control (p < 0.05). Concomitant administration of the ET(A)-receptor antagonist LU135252 led to a significant increase in renin gene expression compared to control or hypoxia alone. ET-1 mRNA increased to 120% after 2 weeks and 173% after 4 weeks of hypoxia (NS), while ET-3 was not affected by hypoxia. We therefore conclude that ETs have a suppressive effect on renal renin gene expression in the setting of chronic hypoxia in rats in vivo.