Abstract
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.
Full Text
The Full Text of this article is available as a PDF (247.4 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Alonso S., Minty A., Bourlet Y., Buckingham M. Comparison of three actin-coding sequences in the mouse; evolutionary relationships between the actin genes of warm-blooded vertebrates. J Mol Evol. 1986;23(1):11–22. doi: 10.1007/BF02100994. [DOI] [PubMed] [Google Scholar]
- Antonipillai I., Vogelsang J., Horton R. Role of atrial natriuretic factor in renin release. Endocrinology. 1986 Jul;119(1):318–322. doi: 10.1210/endo-119-1-318. [DOI] [PubMed] [Google Scholar]
- Beavo J. A. Cyclic nucleotide phosphodiesterases: functional implications of multiple isoforms. Physiol Rev. 1995 Oct;75(4):725–748. doi: 10.1152/physrev.1995.75.4.725. [DOI] [PubMed] [Google Scholar]
- Beierwaltes W. H., Carretero O. A. Nonprostanoid endothelium-derived factors inhibit renin release. Hypertension. 1992 Feb;19(2 Suppl):II68–II73. doi: 10.1161/01.hyp.19.2_suppl.ii68. [DOI] [PubMed] [Google Scholar]
- Beierwaltes W. H. Selective neuronal nitric oxide synthase inhibition blocks furosemide-stimulated renin secretion in vivo. Am J Physiol. 1995 Jul;269(1 Pt 2):F134–F139. doi: 10.1152/ajprenal.1995.269.1.F134. [DOI] [PubMed] [Google Scholar]
- Biel M., Zong X., Hofmann F. Molecular diversity of cyclic nucleotide-gated cation channels. Naunyn Schmiedebergs Arch Pharmacol. 1995 Dec;353(1):1–10. doi: 10.1007/BF00168909. [DOI] [PubMed] [Google Scholar]
- Briggs J. P., Schnermann J. B. Whys and wherefores of juxtaglomerular apparatus function. Kidney Int. 1996 Jun;49(6):1724–1726. doi: 10.1038/ki.1996.255. [DOI] [PubMed] [Google Scholar]
- Butt E., Nolte C., Schulz S., Beltman J., Beavo J. A., Jastorff B., Walter U. Analysis of the functional role of cGMP-dependent protein kinase in intact human platelets using a specific activator 8-para-chlorophenylthio-cGMP. Biochem Pharmacol. 1992 Jun 23;43(12):2591–2600. doi: 10.1016/0006-2952(92)90148-c. [DOI] [PubMed] [Google Scholar]
- Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
- Della Bruna R., Kurtz A., Schricker K. Regulation of renin synthesis in the juxtaglomerular cells. Curr Opin Nephrol Hypertens. 1996 Jan;5(1):16–19. doi: 10.1097/00041552-199601000-00005. [DOI] [PubMed] [Google Scholar]
- Deng X., Welch W. J., Wilcox C. S. Renal vasoconstriction during inhibition of NO synthase: effects of dietary salt. Kidney Int. 1994 Sep;46(3):639–646. doi: 10.1038/ki.1994.316. [DOI] [PubMed] [Google Scholar]
- Ehmke H., Persson P. B., Just A., Nafz B., Seyfarth M., Hackenthal E., Kirchheim H. R. Physiological concentrations of ANP exert a dual regulatory influence on renin release in conscious dogs. Am J Physiol. 1992 Sep;263(3 Pt 2):R529–R536. doi: 10.1152/ajpregu.1992.263.3.R529. [DOI] [PubMed] [Google Scholar]
- French P. J., Bijman J., Edixhoven M., Vaandrager A. B., Scholte B. J., Lohmann S. M., Nairn A. C., de Jonge H. R. Isotype-specific activation of cystic fibrosis transmembrane conductance regulator-chloride channels by cGMP-dependent protein kinase II. J Biol Chem. 1995 Nov 3;270(44):26626–26631. doi: 10.1074/jbc.270.44.26626. [DOI] [PubMed] [Google Scholar]
- Fujihara C. K., Michellazzo S. M., de Nucci G., Zatz R. Sodium excess aggravates hypertension and renal parenchymal injury in rats with chronic NO inhibition. Am J Physiol. 1994 May;266(5 Pt 2):F697–F705. doi: 10.1152/ajprenal.1994.266.5.F697. [DOI] [PubMed] [Google Scholar]
- Gambaryan S., Häusler C., Markert T., Pöhler D., Jarchau T., Walter U., Haase W., Kurtz A., Lohmann S. M. Expression of type II cGMP-dependent protein kinase in rat kidney is regulated by dehydration and correlated with renin gene expression. J Clin Invest. 1996 Aug 1;98(3):662–670. doi: 10.1172/JCI118837. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gambaryan S., Wagner C., Smolenski A., Walter U., Poller W., Haase W., Kurtz A., Lohmann S. M. Endogenous or overexpressed cGMP-dependent protein kinases inhibit cAMP-dependent renin release from rat isolated perfused kidney, microdissected glomeruli, and isolated juxtaglomerular cells. Proc Natl Acad Sci U S A. 1998 Jul 21;95(15):9003–9008. doi: 10.1073/pnas.95.15.9003. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Gardes J., Poux J. M., Gonzalez M. F., Alhenc-Gelas F., Menard J. Decreased renin release and constant kallikrein secretion after injection of L-NAME in isolated perfused rat kidney. Life Sci. 1992;50(14):987–993. doi: 10.1016/0024-3205(92)90092-4. [DOI] [PubMed] [Google Scholar]
- Greenberg S. G., He X. R., Schnermann J. B., Briggs J. P. Effect of nitric oxide on renin secretion. I. Studies in isolated juxtaglomerular granular cells. Am J Physiol. 1995 May;268(5 Pt 2):F948–F952. doi: 10.1152/ajprenal.1995.268.5.F948. [DOI] [PubMed] [Google Scholar]
- Hackenthal E., Lang R. E., Bührle C. P. Atrial natriuretic factor stimulates renin release from the isolated rat kidney. J Hypertens Suppl. 1985 Dec;3(3):S323–S325. [PubMed] [Google Scholar]
- Hackenthal E., Paul M., Ganten D., Taugner R. Morphology, physiology, and molecular biology of renin secretion. Physiol Rev. 1990 Oct;70(4):1067–1116. doi: 10.1152/physrev.1990.70.4.1067. [DOI] [PubMed] [Google Scholar]
- Henrich W. L., McAlister E. A., Smith P. B., Lipton J., Campbell W. B. Direct inhibitory effect of atriopeptin III on renin release in primate kidney. Life Sci. 1987 Jul 20;41(3):259–264. doi: 10.1016/0024-3205(87)90147-0. [DOI] [PubMed] [Google Scholar]
- Henrich W. L., McAllister E. A., Smith P. B., Campbell W. B. Guanosine 3',5'-cyclic monophosphate as a mediator of inhibition of renin release. Am J Physiol. 1988 Sep;255(3 Pt 2):F474–F478. doi: 10.1152/ajprenal.1988.255.3.F474. [DOI] [PubMed] [Google Scholar]
- Hofmann F., Dostmann W., Keilbach A., Landgraf W., Ruth P. Structure and physiological role of cGMP-dependent protein kinase. Biochim Biophys Acta. 1992 Apr 30;1135(1):51–60. doi: 10.1016/0167-4889(92)90165-8. [DOI] [PubMed] [Google Scholar]
- Jarchau T., Häusler C., Markert T., Pöhler D., Vanderkerckhove J., De Jonge H. R., Lohmann S. M., Walter U. Cloning, expression, and in situ localization of rat intestinal cGMP-dependent protein kinase II. Proc Natl Acad Sci U S A. 1994 Sep 27;91(20):9426–9430. doi: 10.1073/pnas.91.20.9426. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Johnson R. A., Freeman R. H. Renin release in rats during blockade of nitric oxide synthesis. Am J Physiol. 1994 Jun;266(6 Pt 2):R1723–R1729. doi: 10.1152/ajpregu.1994.266.6.R1723. [DOI] [PubMed] [Google Scholar]
- Jover B., Herizi A., Ventre F., Dupont M., Mimran A. Sodium and angiotensin in hypertension induced by long-term nitric oxide blockade. Hypertension. 1993 Jun;21(6 Pt 2):944–948. doi: 10.1161/01.hyp.21.6.944. [DOI] [PubMed] [Google Scholar]
- Kim W. S., Murakami K., Nakayama K. Nucleotide sequence of a cDNA coding for mouse Ren1 preprorenin. Nucleic Acids Res. 1989 Nov 25;17(22):9480–9480. [PMC free article] [PubMed] [Google Scholar]
- King J. A., Lush D. J., Fray J. C. Regulation of renin processing and secretion: chemiosmotic control and novel secretory pathway. Am J Physiol. 1993 Aug;265(2 Pt 1):C305–C320. doi: 10.1152/ajpcell.1993.265.2.C305. [DOI] [PubMed] [Google Scholar]
- Kurtz A. Cellular control of renin secretion. Rev Physiol Biochem Pharmacol. 1989;113:1–40. doi: 10.1007/BFb0032674. [DOI] [PubMed] [Google Scholar]
- Kurtz A., Della Bruna R., Pfeilschifter J., Taugner R., Bauer C. Atrial natriuretic peptide inhibits renin release from juxtaglomerular cells by a cGMP-mediated process. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4769–4773. doi: 10.1073/pnas.83.13.4769. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurtz A., Götz K. H., Hamann M., Kieninger M., Wagner C. Stimulation of renin secretion by NO donors is related to the cAMP pathway. Am J Physiol. 1998 Apr;274(4 Pt 2):F709–F717. doi: 10.1152/ajprenal.1998.274.4.F709. [DOI] [PubMed] [Google Scholar]
- Kurtz A., Götz K. H., Hamann M., Wagner C. Stimulation of renin secretion by nitric oxide is mediated by phosphodiesterase 3. Proc Natl Acad Sci U S A. 1998 Apr 14;95(8):4743–4747. doi: 10.1073/pnas.95.8.4743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kurtz A. Membrane and secretory properties of renal juxtaglomerular granular cells. Clin Exp Pharmacol Physiol. 1997 Jul;24(7):536–540. doi: 10.1111/j.1440-1681.1997.tb01242.x. [DOI] [PubMed] [Google Scholar]
- Lincoln T. M., Cornwell T. L. Intracellular cyclic GMP receptor proteins. FASEB J. 1993 Feb 1;7(2):328–338. doi: 10.1096/fasebj.7.2.7680013. [DOI] [PubMed] [Google Scholar]
- Naess P. A., Christensen G., Kirkebøen K. A., Kiil F. Effect on renin release of inhibiting renal nitric oxide synthesis in anaesthetized dogs. Acta Physiol Scand. 1993 Jun;148(2):137–142. doi: 10.1111/j.1748-1716.1993.tb09543.x. [DOI] [PubMed] [Google Scholar]
- Noble A. R., Abu-Kishk R. A., D'Aloia M. A., Williams B. C., Lush D. J. Cyclic GMP-linked pathway for renin secretion. Kidney Int. 1994 Dec;46(6):1588–1590. doi: 10.1038/ki.1994.454. [DOI] [PubMed] [Google Scholar]
- Obana K., Naruse M., Naruse K., Sakurai H., Demura H., Inagami T., Shizume K. Synthetic rat atrial natriuretic factor inhibits in vitro and in vivo renin secretion in rats. Endocrinology. 1985 Sep;117(3):1282–1284. doi: 10.1210/endo-117-3-1282. [DOI] [PubMed] [Google Scholar]
- Persson P. B., Baumann J. E., Ehmke H., Hackenthal E., Kirchheim H. R., Nafz B. Endothelium-derived NO stimulates pressure-dependent renin release in conscious dogs. Am J Physiol. 1993 Jun;264(6 Pt 2):F943–F947. doi: 10.1152/ajprenal.1993.264.6.F943. [DOI] [PubMed] [Google Scholar]
- Pfeifer A., Aszódi A., Seidler U., Ruth P., Hofmann F., Fässler R. Intestinal secretory defects and dwarfism in mice lacking cGMP-dependent protein kinase II. Science. 1996 Dec 20;274(5295):2082–2086. doi: 10.1126/science.274.5295.2082. [DOI] [PubMed] [Google Scholar]
- Pfeifer A., Klatt P., Massberg S., Ny L., Sausbier M., Hirneiss C., Wang G. X., Korth M., Aszódi A., Andersson K. E. Defective smooth muscle regulation in cGMP kinase I-deficient mice. EMBO J. 1998 Jun 1;17(11):3045–3051. doi: 10.1093/emboj/17.11.3045. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reid I. A., Chiu Y. J. Nitric oxide and the control of renin secretion. Fundam Clin Pharmacol. 1995;9(4):309–323. doi: 10.1111/j.1472-8206.1995.tb00505.x. [DOI] [PubMed] [Google Scholar]
- Romero J. C., Lahera V., Salom M. G., Biondi M. L. Role of the endothelium-dependent relaxing factor nitric oxide on renal function. J Am Soc Nephrol. 1992 Mar;2(9):1371–1387. doi: 10.1681/ASN.V291371. [DOI] [PubMed] [Google Scholar]
- Sandberg M., Natarajan V., Ronander I., Kalderon D., Walter U., Lohmann S. M., Jahnsen T. Molecular cloning and predicted full-length amino acid sequence of the type I beta isozyme of cGMP-dependent protein kinase from human placenta. Tissue distribution and developmental changes in rat. FEBS Lett. 1989 Sep 25;255(2):321–329. doi: 10.1016/0014-5793(89)81114-7. [DOI] [PubMed] [Google Scholar]
- Sansom S. C., Stockand J. D., Hall D., Williams B. Regulation of large calcium-activated potassium channels by protein phosphatase 2A. J Biol Chem. 1997 Apr 11;272(15):9902–9906. doi: 10.1074/jbc.272.15.9902. [DOI] [PubMed] [Google Scholar]
- Schnackenberg C. G., Tabor B. L., Strong M. H., Granger J. P. Inhibition of intrarenal NO stimulates renin secretion through a macula densa-mediated mechanism. Am J Physiol. 1997 Mar;272(3 Pt 2):R879–R886. doi: 10.1152/ajpregu.1997.272.3.R879. [DOI] [PubMed] [Google Scholar]
- Scholz H., Hamann M., Götz K. H., Kurtz A. Role of calcium ions in the pressure control of renin secretion from the kidneys. Pflugers Arch. 1994 Sep;428(2):173–178. doi: 10.1007/BF00374855. [DOI] [PubMed] [Google Scholar]
- Scholz H., Kurtz A. Involvement of endothelium-derived relaxing factor in the pressure control of renin secretion from isolated perfused kidney. J Clin Invest. 1993 Mar;91(3):1088–1094. doi: 10.1172/JCI116266. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schricker K., Hegyi I., Hamann M., Kaissling B., Kurtz A. Tonic stimulation of renin gene expression by nitric oxide is counteracted by tonic inhibition through angiotensin II. Proc Natl Acad Sci U S A. 1995 Aug 15;92(17):8006–8010. doi: 10.1073/pnas.92.17.8006. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Schricker K., Kurtz A. Liberators of NO exert a dual effect on renin secretion from isolated mouse renal juxtaglomerular cells. Am J Physiol. 1993 Aug;265(2 Pt 2):F180–F186. doi: 10.1152/ajprenal.1993.265.2.F180. [DOI] [PubMed] [Google Scholar]
- Skøtt O., Briggs J. P. Direct demonstration of macula densa-mediated renin secretion. Science. 1987 Sep 25;237(4822):1618–1620. doi: 10.1126/science.3306925. [DOI] [PubMed] [Google Scholar]
- Sugimoto T., Haneda M., Togawa M., Isono M., Shikano T., Araki S., Nakagawa T., Kashiwagi A., Guan K. L., Kikkawa R. Atrial natriuretic peptide induces the expression of MKP-1, a mitogen-activated protein kinase phosphatase, in glomerular mesangial cells. J Biol Chem. 1996 Jan 5;271(1):544–547. doi: 10.1074/jbc.271.1.544. [DOI] [PubMed] [Google Scholar]
- Takagi M., Takagi M., Franco-Saenz R., Mulrow P. J. Effect of atrial natriuretic peptide on renin release in a superfusion system of kidney slices and dispersed juxtaglomerular cells. Endocrinology. 1988 Apr;122(4):1437–1442. doi: 10.1210/endo-122-4-1437. [DOI] [PubMed] [Google Scholar]
- Uhler M. D. Cloning and expression of a novel cyclic GMP-dependent protein kinase from mouse brain. J Biol Chem. 1993 Jun 25;268(18):13586–13591. [PubMed] [Google Scholar]
- Vidal M. J., Romero J. C., Vanhoutte P. M. Endothelium-derived relaxing factor inhibits renin release. Eur J Pharmacol. 1988 May 10;149(3):401–402. doi: 10.1016/0014-2999(88)90679-6. [DOI] [PubMed] [Google Scholar]
- Wang X., Robinson P. J. Cyclic GMP-dependent protein kinase and cellular signaling in the nervous system. J Neurochem. 1997 Feb;68(2):443–456. doi: 10.1046/j.1471-4159.1997.68020443.x. [DOI] [PubMed] [Google Scholar]
- Wernet W., Flockerzi V., Hofmann F. The cDNA of the two isoforms of bovine cGMP-dependent protein kinase. FEBS Lett. 1989 Jul 17;251(1-2):191–196. doi: 10.1016/0014-5793(89)81453-x. [DOI] [PubMed] [Google Scholar]
- White R. E., Lee A. B., Shcherbatko A. D., Lincoln T. M., Schonbrunn A., Armstrong D. L. Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation. Nature. 1993 Jan 21;361(6409):263–266. doi: 10.1038/361263a0. [DOI] [PubMed] [Google Scholar]
- Yamada S. S., Sassaki A. L., Fujihara C. K., Malheiros D. M., De Nucci G., Zatz R. Effect of salt intake and inhibitor dose on arterial hypertension and renal injury induced by chronic nitric oxide blockade. Hypertension. 1996 May;27(5):1165–1172. doi: 10.1161/01.hyp.27.5.1165. [DOI] [PubMed] [Google Scholar]
- Zhou X. B., Ruth P., Schlossmann J., Hofmann F., Korth M. Protein phosphatase 2A is essential for the activation of Ca2+-activated K+ currents by cGMP-dependent protein kinase in tracheal smooth muscle and Chinese hamster ovary cells. J Biol Chem. 1996 Aug 16;271(33):19760–19767. doi: 10.1074/jbc.271.33.19760. [DOI] [PubMed] [Google Scholar]