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Vasoconstrictor endothelin receptors characterized in human renal artery and vein in vitro
Author(s) -
Maguire Janet J.,
Kuc Rhoda E.,
O'Reilly Gillian,
Davenport Anthony P.
Publication year - 1994
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 - 10.1111/j.1476-5381.1994.tb16172.x
Subject(s) - vasoconstriction , endothelin receptor , receptor , renal vein , renal artery , endothelin 1 , endocrinology , kidney , vein , medicine , endothelins , artery , in vitro , biology , chemistry , biochemistry
1 We have identified the endothelin receptors present in the media of human main stem renal artery and vein and characterized the subtypes mediating vasoconstriction in these blood vessels in vitro . 2 Messenger RNA encoding both ET A and ET B receptors was identified in the smooth muscle layer of human renal artery and vein by reverse transcriptase‐polymerase chain reaction assay. In cryostat‐cut cross‐sections of both vessels autoradiographical visualisation suggested a majority of ET A receptors. Intense binding was obtained to the non‐selective ligand [ 125 I]‐ET‐1 and the ET A ‐selective [ 125 I]‐PD151242 but only weak labelling of sites by the ET B ‐selective [ 125 I]‐BQ3020. 3 ET‐1 potently constricted renal artery and vein preparations with EC 50 values of 4.06 n m and 1.00 n m , respectively. Sarafotoxin 6b was approximately ten times less potent than ET‐1 with EC 50 values of 36.3 n m and 13.8 n m respectively. In the renal artery, ET‐3 and sarafotoxin 6c showed little or no activity up to 300 n m . Responses to these peptides were more variable in the renal vein. Preparations from three individuals did not respond to ET‐3 but in three further cases, although ET‐3 was much less potent than ET‐1, full dose‐response curves were obtained. S6c elicited dose‐related contractions in vein preparations from 5/6 individuals and although more potent than ET‐1, the maximum response was 30–60% of that obtained to ET‐1. 4 ET‐1‐induced vasoconstriction of renal artery and vein was antagonized by the ET A ‐selective, BQ123 (3–10μ m ). The dose‐response curves to ET‐1 were displaced in a parallel rightward fashion with no attenuation of the maximum responses. pA 2 values were estimated to be 6.8 ± 0.1 and 6.8 ± 0.4 for artery and vein respectively. 5 These data suggest that mRNA encoding both ET A and ET B receptors is present in the media of human main stem renal artery and vein. However, autoradiographical studies indicate that the majority of ET receptors expressed are of the ET A subtype. The relative potencies of ET‐1 and ET‐3 as vasoconstrictors of renal blood vessels in vitro is consistent with this being an ET A ‐mediated response, and therefore whilst responses to S6c indicate that constrictor ET B receptors may be present in renal veins from some individuals these are likely to be of less importance in these blood vessels.