Endothelin-1 inhibits induction of nitric oxide synthase and GTP cyclohydrolase I in rat mesangial cells

Pharmacology
J HirahashiT Saruta

Abstract

To investigate the interaction between endothelin (ET) and the nitric oxide system, we examined the effects of ET-1 and ET-3 on the induction of inducible nitric oxide synthase (iNOS) and guanosine triphosphate cyclohydrolase I (GTP:CHI), the rate-limiting enzyme of de novo synthesis of the cofactor tetrahydrobiopterin (BH4), in rat mesangial cells. ET-1 inhibited the nitrite accumulation induced by a combination of interleukin-1 beta, tumor necrosis factor-alpha, and lipopolysaccharide in a concentration-dependent manner. The inhibitory effect of ET-3 was less potent than that of ET-1. A selective ETA antagonist, BQ-485, and an ETA and ETB antagonist, TAK-044, abolished the inhibitory effects of ET-1, whereas the selective ETB antagonist BQ-788 had no effect on the inhibition produced by ET-1. These observations indicate that ET-1 inhibits cytokine-stimulated nitrite accumulation through the ETA receptor. Western blot analysis showed that the suppression of nitrite accumulation was accompanied by a decrease in iNOS protein. Northern blot analysis showed that ET-1 inhibited the expression of both iNOS and GTP:CHI mRNA. In conclusion, ET-1 inhibits cytokine-stimulated nitric oxide production through the ETA receptor by suppressi...Continue Reading

Citations

Jul 23, 2003·Experimental Eye Research·Renyi WuIvan O Haefliger
Jun 1, 2002·Molecular and Cellular Endocrinology·Isao KuriharaTakao Saruta
Mar 14, 2002·The Journal of Alternative and Complementary Medicine : Research on Paradigm, Practice, and Policy·Nathan L Currier, Sandra C Miller
Jan 21, 2011·Physiological Reviews·Donald E KohanDavid M Pollock
Jul 4, 2003·British Journal of Pharmacology·Christelle Mérial-KienyMichel Félétou
May 13, 2015·Seminars in Nephrology·Matthias Barton, Andrey Sorokin
Dec 11, 1999·Proceedings of the Association of American Physicians·M Noris, G Remuzzi
Aug 10, 2000·American Journal of Hypertension·H ZhaoJ P Porter
Sep 5, 2003·American Journal of Physiology. Renal Physiology·Andrey Sorokin, Donald E Kohan

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