Premium
Cyclosporine A‐induced increase in glomerular cyclic GMP in rats and the involvement of the endothelin B receptor
Author(s) -
Tack Ivan,
MarinCastano Encarna,
Bascands JeanLoup,
Pecher Christiane,
Ader JeanLouis,
Girolami JeanPierre
Publication year - 1997
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 - 10.1038/sj.bjp.0701153
Subject(s) - medicine , endocrinology , in vivo , endothelin receptor , endothelin 1 , antagonist , chemistry , receptor antagonist , stimulation , sodium nitroprusside , receptor , renal glomerulus , kidney , biology , nitric oxide , glomerulonephritis , microbiology and biotechnology
A transient two fold increase in the cyclic GMP content was observed in rat freshly isolated glomeruli 6 to 9 h after a single subcutaneous injection of 20 mg kg −1 cyclosporine A (CsA) in conscious animals.In vitro stimulation with endothelin 3 (ET‐3) of isolated glomeruli obtained from CsA‐untreated rats resulted in a dose‐dependent increase in cyclic GMP content. The increase observed with 10 n M ET‐3 was similar to that observed in glomeruli isolated 9 h after in vivo CsA administration. The rise in glomerular cyclic GMP content after in vivo CsA injection was prevented by in vivo treatment with L ‐NAME (10 mg kg −1 ) or by in vitro calcium deprivation of the incubation medium. The stimulating effects of CsA on glomerular cyclic GMP content were inhibited by in vivo administration of the ET B receptor antagonist BQ‐788 (2 mg kg −1 ) but not by the ET A receptor antagonist BQ‐123 (2 mg kg −1 ). The maximum increase in glomerular cyclic GMP content induced in vitro by acetylcholine (100 μ M ) and by ET‐3 (100 n M ) was slightly lower (approximately by 20–25%, P <0.05) in glomeruli from CsA‐treated rats than in glomeruli from untreated rats. In contrast, the maximum increase achieved with 1 μ M sodium nitroprusside was similar in both groups. A single subcutaneous injection of CsA did not significantly alter the glomerular mRNA expression of constitutive endothelial NO synthase (eNOS), as evaluated by RT–PCR, whereas the mRNA expression of the inducible NO synthase (iNOS), which follows pretreatment with lipopolysaccharide, was prevented. These results indicate that in vivo administration of a single dose of cyclosporine A transiently increases the cyclic GMP content of freshly isolated glomeruli, and that activation of ET B receptors and stimulation of the NO pathway are involved in this process. Furthermore, a single administration of CsA does not impair eNOS mRNA expression and only slightly reduces NO‐dependent glomerular cyclic GMP production.