Summary
In excretion studies in dogs it was found that cyclic guanosine-3′∶5′-monophosphate (cGMP) was eliminated by glomerular filtration only. If there is any permeability of the tubule cells to exogenous cGMP, it must be very low. cGMP (5×10−5 moles) injected into the thoracic aorta of rats induced an increase of the renal electrolyte excretion. During the first 5 min after cGMP urine volune, sodium, potassium, and calcium excretion rates were elevated 2-to3-fold. There was also an increase of the glomerular filtration rate (GFR) but this was not statistically signifikant. In micropuncture experiments the intratubular administration of cGMP (10−2 M) into the proximal convoluted tubule delayed the half time (t 1/2) from 8.7 sec, (controls) to 13.8 sec, indicating a decrease of the tubular reabsorption capacity. We conclude that the diuretic action of cGMP is based on a decrease of tubular electrolyte reabsorption. The small increase of GFR may be an additional factor in the diuretic action of cGMP.
References
Boehme, E.: Guanyl-cyclase, Bildung von Guanosin-3′∶5′ monophosphate in Niere und anderen Geweben der Ratte. Europ. J. Biochem. 14, 421–429 (1970)
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. 49, 2222–2236 (1970)
Chinard, F. P.: Comparative renal excretions of glomerular substances following instantaneous injection into renal artery. Amer. J. Physiol. 180, 617–619 (1955)
Führ, J., Kaczmarczyk, J., Krüttgen, C. D.: Eine einfache Methode zur Inulin-bestimmung für Nieren-Clearance-Untersuchungen bei Stoffwechselgesunden und Diabetikern. Klin. Wschr. 33, 729–730 (1955)
Fülgraff, G., Heidenreich, O.: Mikropunktionsuntersuchungen über die Wirkung von Calciumionen auf die Resorptionskapazität und auf die prozentuale Resorption im proximalen Konvolut von Ratten. Naunyn-Schmiedebergs Arch. Pharmak. ex. path. 258, 440–451 (1967)
Fülgraff, G., Heidenreich, O., Heintze, K., Osswald, H.: Die Wirkung von α- und β-Sympathomimetica und Sympatholytica auf die renale Exkretion von Flüssigkeit und Elektrolyten in Ausscheidungs- und Mikropunktionsversuchen an Ratten. Naunyn-Schmiedebergs Arch. Pharmak. exp. Path. 262, 295–308 (1969)
George, W. J., Wilkerson, R. D., Kadowitz, P. J.: Influence of acetylcholine on contractile force and cyclic nucleotide levels in the isolated perfused rat heart. J. Pharmacol. exp. Ther. 184, 228–235 (1973)
Gertz, K. H.: Transtubuläre Natriumchloridflüsse und Permeabilität für Nicht-elektrolyte im proximalen und distalen Konvolut der Rattenniere. Pflügers Arch. ges. Physiol. 276, 336–356 (1963)
Goldberg, N. D., Dietz, S. B., O'Toole, A. G.: Cyclic guanosine-3′∶5′-monophosphate in mammalian tussies and urine. J. biol. Chem. 244, 4458–4466 (1969)
Goodman, A. D., Pagliara, A. S., Steiner, A. L.: Effects of acidosis and alkalosis on 3′∶5′-guanosine monophosphate and 3′∶5′-adenosine monophosphate in renal cortex. Amer. J. Physiol. 223, 620–625 (1972)
Györy, A. Z.: Reexamination of the split oil droplet method as applied to the kidney tubules. Pflügers Arch. 324, 328–343 (1971)
Hardman, J. G., Sutherland, E. W.: Guanyl-cyclase an enzyme catalysing the formation of guanosine-3′∶5′-monophosphate from guanosine triphosphate. J. biol. Chem. 244, 6363–6370 (1969)
Hierholzer, K.: Intracellular action of aldosterone on sodium transport. In: K. Thurau and Jahrmärker (Hrsg.): Renal transport and diuretics, p. 153. Berlin-Heidelberg-New York: Springer 1969
Kuo, J. F., Lee, T. P., Reyes, P. L., Walton, K. G., Donnelly, T. E., Grenngard, P.: Cyclic nucleotide-dependent protein kinases. An assay method for the measurement of guanosine 3′,5′-monophosphate in various biological materials and a study of agents regulating its levels in heart and brain. J. biol. Chem. 247, 16–22 (1972)
Pagliara, A. S., Goodman, A. D.: Effect of 3′∶5′-GMP and 3′∶5′-IMP on production of glucose and ammonia by renal cortex. Amer. J. Physiol. 218, 1301–1306 (1970)
Phillips, R. A., Peters, J. P., van Slyke, D. D.: Quantitative Clinical Chemistry, Vol. 2: Methods (Army ed.). Baltimore: Williams and Wilkins 1943
Pinter, G. G., O'Morchoe, C. C. C., Sikand, R. S.: Effect of acetylcholine on urinary electrolyte excretion. Amer. J. Physiol. 215, 1067–1081 (1968)
Steinhausen, M.: Eine Methode zur Differenzierung proximaler und distaler Tubuli der Nierenrinde von Ratten in vivo und ihre Anwendung zur Bestimmung tubulärer Strömungsgeschwindigkeiten. Pflügers Arch. ges. Physiol. 277, 23–35 (1963)
Author information
Authors and Affiliations
Additional information
Supported by Deutsche Forschungsgemeinschaft.
Rights and permissions
About this article
Cite this article
Osswald, H., Jacobs, O. Cyclic guanosine-3′∶5′-monophosphate induced diuresis in rats. Naunyn-Schmiedeberg's Arch. Pharmacol. 284, 207–214 (1974). https://doi.org/10.1007/BF00501123
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00501123