Cyclosporine A-induced increase in glomerular cyclic GMP in rats and the involvement of the endothelinB receptor

British Journal of Pharmacology
I TackJ P Girolami

Abstract

1. 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. 2.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 nM ET-3 was similar to that observed in glomeruli isolated 9 h after in vivo CsA administration. 3. 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. 4. The stimulating effects of CsA on glomerular cyclic GMP content were inhibited by in vivo administration of the ETB receptor antagonist BQ-788 (2 mg kg-1) but not by the ETA receptor antagonist BQ-123 (2 mg kg-1). 5. The maximum increase in glomerular cyclic GMP content induced in vitro by acetylcholine (100 microM) and by ET-3 (100 nM) 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 microM sodium nitroprusside was...Continue Reading

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Citations

Feb 8, 2003·Antioxidants & Redox Signaling·José M Valdivielso, Roland C Blantz
Feb 19, 2004·American Journal of Physiology. Renal Physiology·Sylvia NotenboomRosalinde Masereeuw
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Feb 8, 2002·American Journal of Physiology. Renal Physiology·Sylvia NotenboomRosalinde Masereeuw
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Jan 22, 2005·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·S Remzi Erdem, Meral Tuncer

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