ETA and ETB receptors differentially modulate afferent and efferent arteriolar responses to endothelin. Br J Pharmacol 2005 Dec;146(7):1019-26
Date
10/19/2005Pubmed ID
16231007Pubmed Central ID
PMC1751231DOI
10.1038/sj.bjp.0706412Scopus ID
2-s2.0-28444465856 (requires institutional sign-in at Scopus site) 81 CitationsAbstract
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 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. Baseline afferent arteriolar diameter was similar in all groups and averaged 17.8+/-0.6 microm (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%. 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. 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.
Author List
Inscho EW, Imig JD, Cook AK, Pollock DMMESH terms used to index this publication - Major topics in bold
AnimalsArterioles
Dose-Response Relationship, Drug
Endothelin A Receptor Antagonists
Endothelin B Receptor Antagonists
Endothelin-1
Endothelins
Male
Peptide Fragments
Pyrrolidines
Rats
Rats, Sprague-Dawley
Receptor, Endothelin A
Receptor, Endothelin B
Vasoconstriction
Viper Venoms