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ET A and ET B receptors differentially modulate afferent and efferent arteriolar responses to endothelin
Author(s) -
Inscho Edward W,
Imig John D,
Cook Anthony K,
Pollock David M
Publication year - 2005
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0706412
Subject(s) - afferent arterioles , efferent , chemistry , endocrinology , vasoconstriction , endothelin receptor , medicine , receptor , agonist , blockade , afferent , angiotensin ii , biology
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