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- Title
Endothelin type A and B receptors in the control of afferent and efferent arterioles in mice.
- Authors
Schildroth, Janice; Rettig-Zimmermann, Juliane; Kalk, Philipp; Steege, Andreas; Fähling, Michael; Sendeski, Mauricio; Paliege, Alexander; Lai, En Yin; Bachmann, Sebastian; Persson, Pontus B.; Hocher, Berthold; Patzak, Andreas
- Abstract
Background. Endothelin 1 contributes to renal blood flow control and pathogenesis of kidney diseases. The differential effects, however, of endothelin 1 (ET-1) on afferent (AA) and efferent arterioles (EA) remain to be established.Methods. We investigated endothelin type A and B receptor (ETA-R, ETB-R) functions in the control of AA and EA. Arterioles of ETB-R deficient, rescued mice [ETB(−/−)] and wild types [ETB(+/+)] were microperfused.Results. ET-1 constricted AA stronger than EA in ETB(−/−) and ETB(+/+) mice. Results in AA: ET-1 induced similar constrictions in ETB(−/−) and ETB(+/+) mice. BQ-123 (ETA-R antagonist) inhibited this response in both groups. ALA-ET-1 and IRL1620 (ETB-R agonists) had no effect on arteriolar diameter. L-NAME did neither affect basal diameters nor ET-1 responses. Results in EA: ET-1 constricted EA stronger in ETB(+/+) compared to ETB(−/−). BQ-123 inhibited the constriction completely only in ETB(−/−). ALA-ET-1 and IRL1620 constricted only arterioles of ETB(+/+) mice. L-NAME decreased basal diameter in ETB(+/+), but not in ETB(−/−) mice and increased the ET-1 response similarly in both groups. The L-NAME actions indicate a contribution of ETB-R in basal nitric oxide (NO) release in EA and suggest dilatory action of ETA-R in EA.Conclusions. ETA-R mediates vasoconstriction in AA and contributes to vasoconstriction in EA in this mouse model. ETB-R has no effect in AA but mediates basal NO release and constriction in EA. The stronger effect of ET-1 on AA supports observations of decreased glomerular filtration rate to ET-1 and indicates a potential contribution of ET-1 to the pathogenesis of kidney diseases.
- Subjects
ENDOTHELINS; REGULATION of blood circulation; KIDNEY diseases; CARCINOGENESIS; HEMODYNAMICS; NITRIC oxide; LABORATORY mice
- Publication
Nephrology Dialysis Transplantation, 2011, Vol 26, Issue 3, p779
- ISSN
0931-0509
- Publication type
Article
- DOI
10.1093/ndt/gfq534