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.
Schweda
F
F
Clinic and Polyclinic of Internal Medicine II, University of Regensburg, Germany. frank.schweda@klinik.uni-regensburg.de
Schweda
A
A
Pfeifer
M
M
Blumberg
F C
FC
Kammerl
M C
MC
Holmer
S R
SR
Riegger
G A
GA
Krämer
B K
BK
D000818:Animals; D016232:Endothelins / Q000502:physiology*; D005786:Gene Expression Regulation; D000860:Hypoxia / Q000378:metabolism; D007668:Kidney / Q000378:metabolism*; D008297:Male; D010666:Phenylpropionates / Q000494:pharmacology; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D012083:Renin / Q000235:genetics*
D016232:Endothelins; D010666:Phenylpropionates; D011743:Pyrimidines; C107831:darusentan; D012083:Renin