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Cyclic nucleotides in renal tissue and urine during graded expansion of extracellular fluid volume in intact and acutely parathyroidectomized rats

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Research in Experimental Medicine

Summary

The effect of graded extracellular fluid volume expansion (ECVE) on kidney content of cyclic 3′,5′-adenosine monophosphate (cAMP) and cyclic 3′,5′-guanosine monophosphate (cGMP) as well as on the renal electrolyte excretion was studied in 45 rats. ECVE was achieved by i.v. infusion of isotonic saline at rates of 2, 12, and 30 ml/h in intact and acutely parathyroidectomized (PTX) rats. The following results were obtained.

  1. 1.

    cAMP tissue levels during ECVE (2 ml/h) were 3.29 ± 0.38 pmol/mg dry weight and increased to 9.54 ± 1.1 (12 ml/h) and to 23.8 ± 1.9 pmol/mg dry weight (30 ml/h) in intact rats. The kidney in PTX rats did not respond with any changes of cAMP after ECVE.

  2. 2.

    cGMP tissue levels were 0.49 ± 0.12 pmol/mg dry weight at 2 ml/h and were only enhanced to 1.16 ± 0.22 pmol/mg dry weight (P < 0.001) during 30 ml/h in intact rats. In PTX rats no changes in cGMP tissue content could be found.

  3. 3.

    Phosphate excretion increased up to 363 ± 15 nmol/min · 100 g body weight during maximal ECVE and was significantly correlated to cAMP tissue levels (r = 0.89) in intact rats. The slight phosphaturia observed in PTX animals was not correlated with an increase of cAMP and was therefore thought to be PTH-independent.

  4. 4.

    Sodium and calcium excretion did not differ in intact and PTX rats during infusion of 2 and 12 ml/h. During maximal ECVE with 30 ml/h, however, sodium and calcium excretion were lower in PTX rats than in the intact animals. The decreased tubular load of these electrolytes in PTX animals due to a small drop in GFR and lower plasma calcium levels compared to intact animals could account, at least in part, for the reduced electrolyte excretion.

  5. 5.

    No consistent correlation was found between the tissue content of cyclic nucleotides and their urinary excretion rates.

It is concluded that the cyclic nucleotides are not involved in the natriuretic response to ECVE. However, a small effect of PTH on the diuresis during maximal ECVE cannot be ruled out. The urinary excretion rates of cyclic nucleotides poorly reflect their corresponding tissue levels. The close correlation between phosphaturia and tissue cAMP levels in intact rats support the concept that parathyroid hormone induced phosphaturia is initiated by cAMP.

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Authors and Affiliations

  1. Department of Pharmacology, Medical Faculty of the Rheinisch-Westfälische Technische Hochschule Aachen, Luisenhospital, Boxgraben 99, D-5100, Aachen, Federal Republic of Germany

    A. Hawlina, H. Osswald & B. Hissel (technical assistance)

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  1. A. Hawlina
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  2. H. Osswald
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  3. B. Hissel
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Supported by Deutsche Forschungsgemeinschaft (Os 42/2–4)

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Hawlina, A., Osswald, H. & Hissel, B. Cyclic nucleotides in renal tissue and urine during graded expansion of extracellular fluid volume in intact and acutely parathyroidectomized rats. Res. Exp. Med. 175, 139–148 (1979). https://doi.org/10.1007/BF01851820

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  • DOI: https://doi.org/10.1007/BF01851820

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