ET A and ET B receptors differentially modulate afferent and efferent arteriolar responses to endothelin

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 B receptors to the renal pre‐ and postglomerular arteriolar responses to ET‐1. Experiments determined the effect of selective ET A (A‐127722; 30 n M ) and ET B (A‐192621; 30 n M ) receptor blockade, on arteriolar responses to ET‐1 concentrations of 1 p M to 10 n M in rat kidneys using the isolated juxtamedullary nephron technique. Renal perfusion pressure was set at 110 mmHg. Baseline afferent arteriolar diameter was similar in all groups and averaged 17.8±0.6  μ m ( n =14). In control experiments ( n =6), ET‐1 produced significant concentration‐dependent decreases in arteriolar diameter, with 10 n M ET‐1 decreasing diameter by 85±1%. Selective blockade of ET A receptors ( n =6) prevented ET‐1‐mediated vasoconstriction, except at concentrations of 1 and 10 n M . 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. 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. 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.British Journal of Pharmacology (2005) 146 , 1019–1026. doi: 10.1038/sj.bjp.0706412