Atrial natriuretic peptide reduces cyclic AMP by activating cyclic GMP-stimulated phosphodiesterase in vascular endothelial cells

Journal of Cardiovascular Pharmacology
Y KishiF Numano

Abstract

Bovine aortic endothelial cells contain cyclic GMP-stimulated phosphodiesterase (PDE) regulating intracellular cyclic AMP and cyclic GMP levels. To investigate the roles of this PDE isoform for cyclic AMP hydrolysis in intact endothelial cells (EC), we used an adenine prelabeling method to determine cyclic AMP accumulation in response to agents that might produce effects that increase cyclic GMP levels. Atrial natriuretic peptide (ANP), which dramatically increased cyclic GMP accumulation, reduced cyclic AMP in cultured EC from bovine aorta with or without addition of L-isoproterenol (L-ISO), whereas sodium nitroprusside (SNP) and 8-bromo cyclic GMP had no effect. The reduction in cyclic AMP by ANP was dose dependent (> or = 1.0 nM) and rapid (significant reduction was induced in < or = 15 s) and was abolished when EC were preincubated with 3-isobutyl-1-methylxanthine (IBMX) and HL-725, both nonselective PDE inhibitors. ANP had no effects on adenylate cyclase activity, nor any direct effects on the activities of partially purified cyclic GMP-stimulated PDE isoform or cyclic AMP-specific isoform. However, cyclic AMP hydrolyzing activities of EC were enhanced when EC were pretreated with 0.1 microM ANP. ANP activates cyclic GMP-s...Continue Reading

Citations

Feb 13, 2001·European Journal of Pharmacology·U SimonsenA C Martinez
Jan 29, 1997·Regulatory Peptides·C T Crilley, R Garcia
Jan 6, 1999·The Annals of Thoracic Surgery·R C KingI L Kron
Jun 22, 1999·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·K SadhuS L Wolda
Feb 22, 2008·Journal of Cardiovascular Pharmacology and Therapeutics·Takashi AshikagaMitsuaki Isobe
Dec 8, 2007·Journal of Cellular Physiology·Anna A BirukovaKonstantin G Birukov

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