The studies were carried out to investigate the role of ETA- and ETB-receptors (ETA-R, ETB-R) in afferent (AF) and efferent arterioles (EF) using ETB-deficient (ko) and wild-type mice (WT). Cumulative dose-response-curves to ET-1 (10-12 -10-7 mol/L) were measured in isolated, perfused AF and EF, as well as during ETA-R-blockade in AF. Further, the ETA-R expression in the whole kidney was examined using real-time RT-PCR.

Results: 1. AF showed a concentration-dependent constriction to ET-1 with higher sensitivity in ETB-ko compared with WT. 2. During ETA-R blockade there was no difference in the dose- response-curves in AF comparing both groups. 3. EF of WT responded to ET-1 with a concentration-dependent constriction. 4. EF of ETB-ko did not. 5. ETA-R were down-regulated in the whole kidney of ETB-ko mice compared with WT. In EF, results indicate a vasoconstrictor action of ETB-R. In AF, results point at a predominantly ETA-R mediated vasoconstriction. The higher sensitivity to ET-1 in ETB-ko mice suggest a dilatory action of ETB-R. However, this assumption is not supported by the experiments during ETA-R blockade. The reduced ETA-R- mRNA expression in ETB-ko mice does not fit to the increased ET-1 sensitivity in ETB-ko.