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The effect of endothelins on nitric oxide and prostacyclin production from human umbilical vein, porcine aorta and bovine carotid artery endothelial cells in culture
Author(s) -
White David G.,
Mundin Jason W.,
Sumner Michael J.,
Watts Ian S.
Publication year - 1993
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.1476-5381.1993.tb13739.x
Subject(s) - prostacyclin , endothelins , umbilical vein , nitric oxide , umbilical artery , medicine , aorta , carotid arteries , endothelin receptor , cardiology , endocrinology , chemistry , biology , fetus , biochemistry , pregnancy , in vitro , receptor , genetics
1 This study has investigated the effects of the endothelin isopeptides, endothelin‐1 (ET‐1), ET‐2 and ET‐3 on the production of the endothelium‐derived relaxing factors, nitric oxide (NO) and prostacyclin (PGI 2 ) from primary cultures of endothelial cells obtained from human umbilical vein (HUVECS), porcine aorta (PAECS) and bovine carotid artery (BCAECS). 2 NO generation was assessed indirectly by measuring production of cyclic GMP and PGI 2 formation was measured by radioimmunoassay of 6‐keto PGF 1α . 3 In HUVECS, histamine (1 μ m ) increased cyclic GMP and 6‐keto PGF 1α production by 12.6 ± 2.0 and 4.9 ± 0.7 fold respectively over the corresponding basal values. Haemoglobin (10 μ m ) and the NO synthase inhibitor N G ‐monomethyl‐ l ‐arginine (10 μ m ) significantly inhibited the increase in cyclic GMP formation in response to histamine but had no effect on 6‐keto PGF 1α production. In contrast to histamine, the endothelin isopeptides (ET‐1, ET‐2 and ET‐3; 0.01–1000 n m ) produced no significant change in either cyclic GMP or 6‐keto PGF 1α production in HUVECS. 4 In a separate series of experiments, ET‐3 (0.01–1000 n m ) also failed to produce any significant change in cyclic GMP or 6‐keto PGF 1α production from primary cultures of PAECS and BCAECS. In contrast, bradykinin (0.1 μ m ) and sodium nitroprusside (1 m m ) were used as positive control agents and increased cyclic GMP production in these cells. 5 In conclusion, the endothelin isopeptides do not release NO and PGI 2 from primary cultures of HUVECS, PAECS and BCAECS. This suggests that endothelin receptors are either absent from these cells or are not coupled to NO or PGI 2 production.