Abstract
cGMP generation has been associated with many of the vascular and endocrine actions of atrial natriuretic factor (ANF) in vitro. To examine the role of cGMP as a second messenger for the renal hemodynamic action of ANF in vivo, we measured glomerular filtration rate (GFR) and cGMP concentration in systemic artery, renal vein, and urine as well as in Bowman's space and end-proximal tubule (by free-flow micropuncture) after administration of ANF. ANF increased GFR by 45% and simultaneously induced a greater than 5-fold increase of cGMP concentration in glomerular ultrafiltrate (Bowman's space) when compared to controls. There was no significant increase in either systemic artery or renal vein cGMP concentration. Thus, the source of increased Bowman's space cGMP is not from the blood via filtration but rather from either glomerular mesangial or epithelial cells, which are not in direct contact with the circulation. Although a small amount of tubular handling of cGMP occurred along the length of the nephron, the augmented cGMP production from the glomerulus accounted for most of the 10- to 12-fold higher urinary cGMP excretion observed after ANF administration. Intrarenal arterial infusion of dibutyryl cGMP, but not dibutyryl cAMP, increased GFR in a dose-dependent fashion (from 10 to 1000 microM) by a mechanism similar to that of ANF--an increase in glomerular hydraulic pressure. Thus, ANF markedly stimulated glomerular production of cGMP, which coincided with a marked increase in GFR. Since dibutyryl cGMP itself was capable of increasing GFR, cGMP is the likely second messenger for ANF in vivo.
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- ASHMAN D. F., LIPTON R., MELICOW M. M., PRICE T. D. Isolation of adenosine 3', 5'-monophosphate and guanosine 3', 5'-monophosphate from rat urine. Biochem Biophys Res Commun. 1963 May 22;11:330–334. doi: 10.1016/0006-291x(63)90566-7. [DOI] [PubMed] [Google Scholar]
- Arendshorst W. J., Gottschalk C. W. Glomerular ultrafiltration dynamics: historical perspective. Am J Physiol. 1985 Feb;248(2 Pt 2):F163–F174. doi: 10.1152/ajprenal.1985.248.2.F163. [DOI] [PubMed] [Google Scholar]
- Atlas S. A., Kleinert H. D., Camargo M. J., Januszewicz A., Sealey J. E., Laragh J. H., Schilling J. W., Lewicki J. A., Johnson L. K., Maack T. Purification, sequencing and synthesis of natriuretic and vasoactive rat atrial peptide. Nature. 1984 Jun 21;309(5970):717–719. doi: 10.1038/309717a0. [DOI] [PubMed] [Google Scholar]
- Ballermann B. J., Hoover R. L., Karnovsky M. J., Brenner B. M. Physiologic regulation of atrial natriuretic peptide receptors in rat renal glomeruli. J Clin Invest. 1985 Dec;76(6):2049–2056. doi: 10.1172/JCI112207. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Benfey B. G., Kunos G., Nickerson M. Dissociation of cardiac inotropic and adenylate cyclast activating adrenoceptors. Br J Pharmacol. 1974 Jun;51(2):253–257. doi: 10.1111/j.1476-5381.1974.tb09655.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Blonde L., Wehmann R. E., Steiner A. L. Plasma clearance rates and renal clearance of 3H-labeled cyclic AMP and 3H-labeled cyclic GMP in the dog. J Clin Invest. 1974 Jan;53(1):163–172. doi: 10.1172/JCI107534. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Briggs J. P., Steipe B., Schubert G., Schnermann J. Micropuncture studies of the renal effects of atrial natriuretic substance. Pflugers Arch. 1982 Dec;395(4):271–276. doi: 10.1007/BF00580789. [DOI] [PubMed] [Google Scholar]
- Broadus A. E., Kaminsky N. I., Hardman J. G., Sutherland E. W., Liddle G. W. Kinetic parameters and renal clearances of plasma adenosine 3',5'-monophosphate and guanosine 3',5'-monophosphate in man. J Clin Invest. 1970 Dec;49(12):2222–2236. doi: 10.1172/JCI106441. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Broadus A. E., Mahaffey J. E., Bartter F. C., Neer R. M. Nephrogenous cyclic adenosine monophosphate as a parathyroid function test. J Clin Invest. 1977 Oct;60(4):771–783. doi: 10.1172/JCI108831. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Camargo M. J., Kleinert H. D., Atlas S. A., Sealey J. E., Laragh J. H., Maack T. Ca-dependent hemodynamic and natriuretic effects of atrial extract in isolated rat kidney. Am J Physiol. 1984 Apr;246(4 Pt 2):F447–F456. doi: 10.1152/ajprenal.1984.246.4.F447. [DOI] [PubMed] [Google Scholar]
- Cogan M. G. Atrial natriuretic factor can increase renal solute excretion primarily by raising glomerular filtration. Am J Physiol. 1986 Apr;250(4 Pt 2):F710–F714. doi: 10.1152/ajprenal.1986.250.4.F710. [DOI] [PubMed] [Google Scholar]
- Cogan M. G., Maddox D. A., Lucci M. S., Rector F. C., Jr Control of proximal bicarbonate reabsorption in normal and acidotic rats. J Clin Invest. 1979 Nov;64(5):1168–1180. doi: 10.1172/JCI109570. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cogan M. G., Rector F. C., Jr Determinants of proximal bicarbonate, chloride, and water reabsorption during carbonic anhydrase inhibition. Am J Physiol. 1982 Mar;242(3):F274–F284. doi: 10.1152/ajprenal.1982.242.3.F274. [DOI] [PubMed] [Google Scholar]
- Currie M. G., Geller D. M., Cole B. R., Boylan J. G., YuSheng W., Holmberg S. W., Needleman P. Bioactive cardiac substances: potent vasorelaxant activity in mammalian atria. Science. 1983 Jul 1;221(4605):71–73. doi: 10.1126/science.6857267. [DOI] [PubMed] [Google Scholar]
- Dworkin L. D., Ichikawa I., Brenner B. M. Hormonal modulation of glomerular function. Am J Physiol. 1983 Feb;244(2):F95–104. doi: 10.1152/ajprenal.1983.244.2.F95. [DOI] [PubMed] [Google Scholar]
- Field M., Graf L. H., Jr, Laird W. J., Smith P. L. Heat-stable enterotoxin of Escherichia coli: in vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. Proc Natl Acad Sci U S A. 1978 Jun;75(6):2800–2804. doi: 10.1073/pnas.75.6.2800. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fiscus R. R., Rapoport R. M., Waldman S. A., Murad F. Atriopeptin II elevates cyclic GMP, activates cyclic GMP-dependent protein kinase and causes relaxation in rat thoracic aorta. Biochim Biophys Acta. 1985 Jul 30;846(1):179–184. doi: 10.1016/0167-4889(85)90124-7. [DOI] [PubMed] [Google Scholar]
- Goldberg N. D., Dietz S. B., O'Toole A. G. Cyclic guanosine 3',5'-monophosphate in mammalian tissues and urine. J Biol Chem. 1969 Aug 25;244(16):4458–4466. [PubMed] [Google Scholar]
- Hamet P., Tremblay J., Pang S. C., Garcia R., Thibault G., Gutkowska J., Cantin M., Genest J. Effect of native and synthetic atrial natriuretic factor on cyclic GMP. Biochem Biophys Res Commun. 1984 Sep 17;123(2):515–527. doi: 10.1016/0006-291x(84)90260-2. [DOI] [PubMed] [Google Scholar]
- Huang C. L., Lewicki J., Johnson L. K., Cogan M. G. Renal mechanism of action of rat atrial natriuretic factor. J Clin Invest. 1985 Feb;75(2):769–773. doi: 10.1172/JCI111759. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Ichikawa I., Brenner B. M. Evidence for glomerular actions of ADH and dibutyryl cyclic AMP in the rat. Am J Physiol. 1977 Aug;233(2):F102–F117. doi: 10.1152/ajprenal.1977.233.2.F102. [DOI] [PubMed] [Google Scholar]
- Ignarro L. J., Kadowitz P. J. The pharmacological and physiological role of cyclic GMP in vascular smooth muscle relaxation. Annu Rev Pharmacol Toxicol. 1985;25:171–191. doi: 10.1146/annurev.pa.25.040185.001131. [DOI] [PubMed] [Google Scholar]
- Ishikawa S., Saito T., Okada K., Kuzuya T., Kangawa K., Matsuo H. Atrial natriuretic factor increases cyclic GMP and inhibits cyclic AMP in rat renal papillary collecting tubule cells in culture. Biochem Biophys Res Commun. 1985 Aug 15;130(3):1147–1153. doi: 10.1016/0006-291x(85)91735-8. [DOI] [PubMed] [Google Scholar]
- Matsuoka H., Ishii M., Sugimoto T., Hirata Y., Sugimoto T., Kangawa K., Matsuo H. Inhibition of aldosterone production by alpha-human atrial natriuretic polypeptide is associated with an increase in cGMP production. Biochem Biophys Res Commun. 1985 Mar 29;127(3):1052–1056. doi: 10.1016/s0006-291x(85)80051-6. [DOI] [PubMed] [Google Scholar]
- Sonnenberg H., Cupples W. A., de Bold A. J., Veress A. T. Intrarenal localization of the natriuretic effect of cardiac atrial extract. Can J Physiol Pharmacol. 1982 Sep;60(9):1149–1152. doi: 10.1139/y82-166. [DOI] [PubMed] [Google Scholar]
- Stokes T. J., Jr, McConkey C. L., Jr, Martin K. J. Atriopeptin III increases cGMP in glomeruli but not in proximal tubules of dog kidney. Am J Physiol. 1986 Jan;250(1 Pt 2):F27–F31. doi: 10.1152/ajprenal.1986.250.1.F27. [DOI] [PubMed] [Google Scholar]
- Stryer L. Cyclic GMP cascade of vision. Annu Rev Neurosci. 1986;9:87–119. doi: 10.1146/annurev.ne.09.030186.000511. [DOI] [PubMed] [Google Scholar]
- Tremblay J., Gerzer R., Vinay P., Pang S. C., Béliveau R., Hamet P. The increase of cGMP by atrial natriuretic factor correlates with the distribution of particulate guanylate cyclase. FEBS Lett. 1985 Feb 11;181(1):17–22. doi: 10.1016/0014-5793(85)81105-4. [DOI] [PubMed] [Google Scholar]
- Walter U. Cyclic-GMP-regulated enzymes and their possible physiological functions. Adv Cyclic Nucleotide Protein Phosphorylation Res. 1984;17:249–258. [PubMed] [Google Scholar]
- Winquist R. J., Faison E. P., Waldman S. A., Schwartz K., Murad F., Rapoport R. M. Atrial natriuretic factor elicits an endothelium-independent relaxation and activates particulate guanylate cyclase in vascular smooth muscle. Proc Natl Acad Sci U S A. 1984 Dec;81(23):7661–7664. doi: 10.1073/pnas.81.23.7661. [DOI] [PMC free article] [PubMed] [Google Scholar]
- de Bold A. J., Borenstein H. B., Veress A. T., Sonnenberg H. A rapid and potent natriuretic response to intravenous injection of atrial myocardial extract in rats. Life Sci. 1981 Jan 5;28(1):89–94. doi: 10.1016/0024-3205(81)90370-2. [DOI] [PubMed] [Google Scholar]