Role of cGMP-kinase II in the control of renin secretion and renin expression.
To investigate the roles of the cGMP-dependent protein kinases (cGKs) in the control of the renin system, we studied the regulation of renin in cGKI- or cGKII-deficient mice in vivo and in vitro. Renal renin mRNA levels both under stimulatory (low-salt diet plus ramipril) and inhibitory (high-salt diet) conditions were not different between wild-type and cGKI-/- mice, but were significantly elevated in cGKII-/- mice under all experimental conditions. In primary cultures of renal juxtaglomerular cells (JG) established from wild-type, cGKI-/-, and cGKII-/- mice, the adenylate cyclase activator forskolin stimulated renin secretion similarly in all genotypes tested. 8-bromo-cGMP attenuated basal and forskolin-stimulated renin secretion in cultures from wild-type and cGKI-/-, but had no effect in cells isolated from cGKII-/- mice. Activation of cGKs by 8-bromo-cGMP decreased renin secretion from the isolated perfused rat kidney, independent of prestimulation by beta-adrenoreceptor activation, macula densa inhibition, reduced perfusion pressure, or by a nominally calcium-free perfusate. Taken together, these findings suggest that activation of cGKII has a general inhibitory effect on renin secretion from renal JG cells.
Wagner
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C
Institut für Physiologie I, Universität Regensburg, D-93040 Regensburg, Germany. charlotte.schmid@vkl.uni-regensburg.de
Pfeifer
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A
Ruth
P
P
Hofmann
F
F
Kurtz
A
A
D000818:Animals; D002478:Cells, Cultured; D005576:Colforsin / Q000494:pharmacology; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000494:pharmacology; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D017869:Cyclic GMP-Dependent Protein Kinases / Q000172:deficiency / Q000378:metabolism*; D004789:Enzyme Activation; D005786:Gene Expression Regulation; D066298:In Vitro Techniques; D007606:Juxtaglomerular Apparatus / Q000378:metabolism*; D051379:Mice; D008817:Mice, Mutant Strains; D010477:Perfusion; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D012083:Renin / Q000235:genetics / Q000378:metabolism*; D012084:Renin-Angiotensin System / Q000502:physiology*
D012333:RNA, Messenger; D005576:Colforsin; C016276:8-bromocyclic GMP; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D062967:Cyclic GMP-Dependent Protein Kinase Type II; D017869:Cyclic GMP-Dependent Protein Kinases; C569720:Prkg1 protein, mouse; C569730:Prkg2 protein, mouse; C569732:Prkg2 protein, rat; D012083:Renin; D006152:Cyclic GMP