title: Effect of angiotensin II on ANP-dependent guanylyl cyclase activity in cultured mouse and rat podocytes.
abstract: The presence of a well-developed contractile apparatus is the feature determining major roles of podocytes in the renal glomeruli. Receptors for a variety of vasoactive hormones are expressed in these cells; however, most of the signaling pathways are still unknown and remain to be elucidated. Angiotensin II (Ang II) and atrial natriuretic peptide (ANP), due to their opposite action, are the major modulators of glomerular filtration. In podocytes, Ang II induces rise in intracellular calcium concentration, whereas ANP stimulates generation of cGMP. The present study was designed to check whether ANP-stimulated cGMP synthesis in podocytes might be affected by Ang II. Cultured rat (RP) and mouse (MP) podocytes were stimulated with ANP, in the absence or presence of Ang II and cyclic GMP was determined by RIA method. Co-incubation of podocytes with ANP and Ang II caused significant (p < 0.01) suppression of ANP-dependent cGMP generation. The effect was prevented by saralasin, an inhibitor of angiotensin receptors. Phorbol-12-myristate-13-acetate (PMA) mimicked, whereas chelerythrine reversed inhibitory effect of Ang II. In conclusion, angiotensin II counteracts ANP-stimulated cGMP synthesis in cultured podocytes. It seems likely that the protein kinase C pathway is involved in this effect.
authors.affiliation: Department of Immunopathology, Medical University of Gdańsk, Warsaw, Poland.
authors.forename: Magdalena
authors.initials: M
authors.lastname: Golos
authors.forename: Barbara
authors.initials: B
authors.lastname: Lewko
authors.forename: Ewa
authors.initials: E
authors.lastname: Bryl
authors.forename: Jacek M
authors.initials: JM
authors.lastname: Witkowski
authors.forename: Anna
authors.initials: A
authors.lastname: Dubaniewicz
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Olszewska
authors.forename: Elzbieta
authors.initials: E
authors.lastname: Latawiec
authors.forename: Stefan
authors.initials: S
authors.lastname: Angielski
authors.forename: Jan
authors.initials: J
authors.lastname: Stepinski
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D000818:Animals; D009320:Atrial Natriuretic Factor / Q000378:metabolism*; D002461:Cell Line, Transformed; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000096:biosynthesis; D005260:Female; D006162:Guanylate Cyclase / Q000378:metabolism*; D066298:In Vitro Techniques; D007678:Kidney Glomerulus / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D051379:Mice; D051381:Rats; D017208:Rats, Wistar
chemical_list: D000804:Angiotensin II; D009320:Atrial Natriuretic Factor; D006162:Guanylate Cyclase; D006152:Cyclic GMP