THE EFFECT OF ENDOTHELINS ON NITRIC-OXIDE AND PROSTACYCLIN PRODUCTIONFROM HUMAN UMBILICAL VEIN, PORCINE AORTA AND BOVINE CAROTID-ARTERY ENDOTHELIAL-CELLS IN CULTURE

1 This study has investigated the effects of the endothelin isopeptide s, endothelin-I (ET-1), ET-2 and ET-3 on the production of the endothe lium-derived relaxing factors, nitric oxide (NO) and prostacyclin (PGI 2) from primary cultures of endothelial cells obtained from human umbi lical vein (HUVECS), porcine aorta (PAECS) and bovine carotid artery ( BCAECS). 2 NO generation was assessed indirectly by measuring producti on of cyclic GMP and PGI2 formation was measured by radioimmunoassay o f 6-keto PGF1alpha. 3 In HUVECS, histamine (1 muM) increased cyclic GM P and 6-keto PGF1alpha production by 12.6 +/- 2.0 and 4.9 +/- 0.7 fold respectively over the corresponding basal values. Haemoglobin (10 muM ) and the NO synthase inhibitor N(G)-monomethyl-L-arginine (10 muM) si gnificantly inhibited the increase in cyclic GMP formation in response to histamine but had no effect on 6-keto PGF1alpha production. In con trast to histamine, the endothelin isopeptides (ET-1, ET-2 and ET-3; 0 .01-1000 nm) produced no significant change in either cyclic GMP or 6- keto PGF1alpha production in HUVECS. 4 In a separate series of experim ents, ET-3 (0.01-1000 nm) also failed to produce any significant chang e in cyclic GMP or 6-keto PGF1alpha production from primary cultures o f PAECS and BCAECS. In contrast, bradykinin (0.1 muM) and sodium nitro prusside (I mm) were used as positive control agents and increased cyc lic GMP production in these cells. 5 In conclusion, the endothelin iso peptides do not release NO and PGI2 from primary cultures of HUVECS, P AECS and BCAECS. This suggests that endothelin receptors are either ab sent from these cells or are not coupled to NO or PGI2 production.