1 The segment-specific actions of endothelin peptides and agonists have not been thoroughly investigated in the renal microcirculation. The current studies were performed to assess the relative contribution of ET A and ET A receptors to the renal pre- and postglomerular arteriolar responses to ET-1. 2 Experiments determined the effect of selective ET A (A-127722; 30 nM) and ET B (A-192621; 30 nM) receptor blockade, on arteriolar responses to ET-1 concentrations of 1 pM to 10 nM in rat kidneys using the isolated juxtamedullary nephron technique. Renal perfusion pressure was set at 110 mmHg. 3 Baseline afferent arteriolar diameter was similar in all groups and averaged 17.8±0.6 μm (n=14). In control experiments (n=6), ET-1 produced significant concentration-dependent decreases in arteriolar diameter, with 10 nM ET-1 decreasing diameter by 85±1%. 4 Selective blockade of ET A receptors (n=6) prevented ET-1-mediated vasoconstriction, except at concentrations of 1 and 10 nM. Similarly, the vasoconstrictor profile was right shifted during selective ET B receptor blockade (n=4). Combined ET A and ET B receptor blockade (n=5) completely abolished afferent arteriolar diameter responses to ET-1. 5 ET B selective agonists (S6c and IRL-1620) produced disparate responses. S6c produced a concentration-dependent vasoconstriction of afferent arterioles. In contrast, S6c produced a concentration-dependent dilation of efferent arterioles that could be blocked with an ET B receptor antagonist. IRL-1620, another ET B agonist, was less effective at altering afferent or efferent diameter and produced a small reduction in pre- and postglomerular arteriolar diameter. 6 These data demonstrate that both ET A and ET B receptors participate in ET-1-mediated vasoconstriction of afferent arterioles. ET B receptor stimulation provides a significant vasodilatory influence on the efferent arteriole. Furthermore, since selective ET A and ET B receptor antagonists abolished preglomerular vasoconstrictor responses at lower ET-1 concentrations, these data support a possible interaction between ET A and ET B receptors in the control of afferent arteriolar diameter. © 2005 Nature Publishing Group All rights reserved.