Display options
Share it on
Full text links
Wiley Free PMC Article

Br J Pharmacol. 1996 Aug;118(8):1995-2000. doi: 10.1111/j.1476-5381.1996.tb15635.x.

Effect of intrarenally infused parathyroid hormone-related protein on renal blood flow and glomerular filtration rate in the anaesthetized rat.

British journal of pharmacology

T Massfelder, N Parekh, K Endlich, C Saussine, M Steinhausen, J J Helwig

Affiliations

  1. Laboratoire de Physiologie Cellulaire Rénale, Faculté de Médecine, Université Louis Pasteur, CJF INSERM 9409, Strasbourg, France.

PMID: 8864534 PMCID: PMC1909869 DOI: 10.1111/j.1476-5381.1996.tb15635.x
Free PMC Article

Abstract

1. Parathyroid hormone-related protein (PTHrP) is expressed in the kidney and acts on vascular PTH/ PTHrP receptors to vasodilate the isolated kidney and to stimulate renin release. However, effects of PTHrP on renal blood flow (RBF) and glomerular filtration rate (GFR) in vivo have not been assessed in the absence of its cardiac, peripheral and central effects. We investigated the renal effects of PTH and PTHrP infused into the left renal artery of anaesthetized rats. 2. Intrarenal infusions, adjusted to generate increasing concentrations of human PTHrP(1-34) and rat PTH(1-34) in renal plasma (2 x 10(-11) to 6 x 10(-9) M) produced a comparable dose-dependent increase in RBF. The rise was 4% at the lowest and 34% at the highest concentrations of peptides. Up to a concentration of 2 x 10(-9) M, mean arterial pressure (MAP) and heart rate were not affected, but at 6 x 10(-9) M, intrarenally infused peptides reached the peripheral circulation, and caused a fall in MAP within a few minutes. While MAP returned to basal value after the last peptide infusion, RBF remained more than 10% above control for at least 30 min. 3. Two competitive PTH/PTHrP receptor antagonists, [Nle8,18, Tyr34]-bPTH(3-34)amide and [Leu11, D-Trp12]-hPTHrP(7-34)amide (2 x 10(-8) M) were devoid of agonist activity, but markedly antagonized the dose-dependent increase in RBF elicited by PTHrP. 4. GFR and urine flow were measured in left PTHrP-infused experimental kidney and right control kidney. Renal PTHrP concentration of 10(-10) M elevated left RBF by 10%, and GFR by 20% without significantly increasing filtration fraction, and increased urine flow by 57%. In the right control kidney GFR and diuresis did not change. 5. The results indicate that PTHrP has similar renal haemodynamic effects as PTH and increases RBF, GFR and diuresis in anaesthetized rats.

References

  1. Am J Physiol. 1995 May;268(5 Pt 2):F967-71 - PubMed
  2. Endocrinology. 1994 Jul;135(1):253-61 - PubMed
  3. Physiol Rev. 1996 Jan;76(1):127-73 - PubMed
  4. Endocrinology. 1989 Aug;125(2):834-41 - PubMed
  5. Naunyn Schmiedebergs Arch Pharmacol. 1989 Aug;340(2):246-51 - PubMed
  6. Endocrinology. 1974 Aug;95(2):621-6 - PubMed
  7. J Biol Chem. 1977 Aug 25;252(16):5847-51 - PubMed
  8. Am J Physiol. 1978 May;234(5):F393-401 - PubMed
  9. Kidney Int. 1981 Oct;20(4):442-51 - PubMed
  10. Am J Cardiol. 1982 Apr 21;49(6):1430-3 - PubMed
  11. Science. 1983 Jun 3;220(4601):1053-5 - PubMed
  12. Eur J Pharmacol. 1984 Jan 27;97(3-4):209-15 - PubMed
  13. J Biol Chem. 1987 May 25;262(15):7151-6 - PubMed
  14. Proc Natl Acad Sci U S A. 1987 Jul;84(14):5048-52 - PubMed
  15. Am J Physiol. 1987 Oct;253(4 Pt 2):R634-9 - PubMed
  16. J Clin Invest. 1987 Dec;80(6):1803-7 - PubMed
  17. Am J Kidney Dis. 1987 Dec;10(6):427-30 - PubMed
  18. Biochem Biophys Res Commun. 1987 Nov 30;149(1):227-32 - PubMed
  19. Endocrinology. 1990 Feb;126(2):721-7 - PubMed
  20. Eur J Pharmacol. 1989 Dec 19;174(2-3):139-51 - PubMed
  21. Endocrinology. 1990 Jul;127(1):491-3 - PubMed
  22. J Pharmacol Exp Ther. 1991 Jan;256(1):110-8 - PubMed
  23. Endocrinology. 1991 Apr;128(4):1927-37 - PubMed
  24. Pharmacology. 1991;42(2):91-6 - PubMed
  25. Endocrinology. 1991 Sep;129(3):1233-42 - PubMed
  26. J Clin Invest. 1991 Dec;88(6):1841-7 - PubMed
  27. Proc Natl Acad Sci U S A. 1992 Apr 1;89(7):2732-6 - PubMed
  28. Endocrinology. 1992 Oct;131(4):1603-11 - PubMed
  29. J Biol Chem. 1993 Jan 25;268(3):1987-94 - PubMed
  30. Life Sci. 1993;53(11):875-81 - PubMed
  31. J Clin Invest. 1993 Dec;92(6):2850-7 - PubMed
  32. Kidney Int. 1993 Oct;44(4):764-73 - PubMed
  33. Biochem Biophys Res Commun. 1994 Mar 15;199(2):547-51 - PubMed
  34. Clin Sci (Lond). 1994 Mar;86(3):245-9 - PubMed
  35. Endocrinology. 1994 May;134(5):2230-6 - PubMed
  36. J Physiol. 1995 Mar 1;483 ( Pt 2):481-90 - PubMed

Substances

MeSH terms

Publication Types

LinkOut - more resources