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The vasodilator action of parathyroid hormone fragments on isolated perfused rat kidney

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Summary

The renal vasodilator responses to various fragments of PTH were quantified on a model of isolated perfused rat kidney (IPK), under non-filtering conditions. The 1–34 fragment of bovine PTH, its Nle analogue and rat PTH, injected in sequential cumulative doses, caused concentration-dependent vasodilatation in the vasculature of the IPK which was preconstricted with prostaglandin F2α. The EC50 of PTH for renal vasodilatation ranged from 1 to 2 nM for all PTH fragments and maximum vasodilatation ranged from 33 to 41% of the maximum vasodilatation induced by papaverine. Renal vasodilatation was not related to prostaglandin release since similar vasodilatation occurred after the inhibition of prostaglandin synthesis with indomethacin. When PTH was administered in single bolus injections, using a separate kidney for each hormone concentration, rather than repeated injections into the same kidney, higher maximum vasodilatations were obtained (64%). These results most likely reflected tachyphylaxis of the renal vasculature to PTH occurring after repeated exposure of a single kidney to the hormone. The antagonist analogue [Nle8,18 Tyr34]-bPTH-(3–34)A shifted the concentration-related response curve to the right, indicating that the renal vasodilator response to rPTH-(1–34) involved specific vascular receptors.

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Abbreviations

AC:

adenylate cyclase

BSA:

bovine serum albumin

IPK:

isolated perfused kidney

bPTH:

bovine PTH (1-34)

rPTH:

rat PTH (1-34)

[Nle8,18, Tyr34]-bPTH-(1-34)A or-(3-34)A:

[Norleucyl8, norleucyl18, tyrosyl34]-bovine PTH-(1-34)amide or -(3-34)amide;

PTH:

parathyroid hormone

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Authors and Affiliations

  1. Institut de Pharmacologie et de Medecine Expímentale (URA DO 589 CNRS), 11, rue Humann, F-67000, Strasbourg, France

    Marie-José Musso, Mariette Barthehnebs & Jean-Louis Imbs

  2. Pavillon Poincaré, Laboratoire de Physiologic Rńae René Leriche, Hospices Civils, B. P. 426, F-67091, Strasbourg Cedex, France

    Martin Plante, Claude Bollack & Jean-Jacques Helwig

Authors
  1. Marie-José Musso
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  2. Mariette Barthehnebs
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  3. Jean-Louis Imbs
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  4. Martin Plante
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  5. Claude Bollack
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  6. Jean-Jacques Helwig
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Musso, MJ., Barthehnebs, M., Imbs, JL. et al. The vasodilator action of parathyroid hormone fragments on isolated perfused rat kidney. Naunyn-Schmiedeberg's Arch Pharmacol 340, 246–251 (1989). https://doi.org/10.1007/BF00168976

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  • DOI: https://doi.org/10.1007/BF00168976

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