ETA and ETB receptors differentially modulate afferent and efferent arteriolar responses to endothelin

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 ETA and ETB receptors to the renal pre- and postglomerular arteriolar responses to ET-1. 2 Experiments determined the effect of selective ETA (A-127722; 30 nM) and ETB (A-192621; 30nm) receptor blockade, on arteriolar responses to ET-1 concentrations of 1 mu m 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 mu m (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 ETA 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 ETB receptor blockade (n = 4). Combined ETA and ETB receptor blockade (n = 5) completely abolished afferent arteriolar diameter responses to ET-1. 5 ETB 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 ETB receptor antagonist. IRL-1620, another ETB 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 ETA and ETB receptors participate in ET-1-mediated vasoconstriction of afferent arterioles. ETB receptor stimulation provides a significant vasodilatory influence on the efferent arteriole. Furthermore, since selective ETA and ETB receptor antagonists abolished preglomerular vasoconstrictor responses at lower ET-1 concentrations, these data support a possible interaction between ETA and ETB receptors in the control of afferent arteriolar diameter.