Skip to main content
PMC home page
The Journal of Physiology logoLink to The Journal of Physiology
. 1995 Mar 1;483(Pt 2):481–490. doi: 10.1113/jphysiol.1995.sp020599

Vascular effects of parathyroid hormone and parathyroid hormone-related protein in the split hydronephrotic rat kidney.

K Endlich 1, T Massfelder 1, J J Helwig 1, M Steinhausen 1
PMCID: PMC1157858  PMID: 7650615

Abstract

1. The effects of locally applied parathyroid hormone-related protein (PTHRP), a putative autocrine/paracrine hormone, on vascular diameters and glomerular blood flow (GBF) in the split hydronephrotic rat kidney were studied. As PTHRP interacts with parathyroid hormone (PTH) receptors in all tissues tested so far, the effects of PTHRP were compared with those of PTH. 2. Preglomerular vessels dilated in a concentration- and time-dependent manner that was almost identical for PTH and PTHRP. A significant preglomerular vasodilation (5-17%) occurred at a threshold concentration of 10(-10) mol l-1 PTH or PTHRP, which raised GBF by 20 +/- 2 and 31 +/- 4%, respectively (means +/- S.E.M., n = 6). PTH or PTHRP (10(-7) mol l-1) increased preglomerular diameters (11-36%) and GBF (60 +/- 10 and 70 +/- 8%, respectively) to near maximum. The most prominent dilatation was located at the interlobular artery and at the proximal afferent arteriole. 3. Efferent arterioles were not affected by either PTH or PTHRP. 4. Estimated concentrations of half-maximal response (EC50) for preglomerular vasodilatation and GBF increase were in the nanomolar to subnanomolar range. 5. After inhibition of angiotensin I-converting enzyme by 2 x 10(-6) mol kg-1 quinapril I.V. (n = 6), 10(-8) mol l-1 PTHRP dilated preglomerular vessels and efferent arterioles (9 +/- 1% proximal and 6 +/- 1% distal). 6. We conclude that the renal vasculature of the hydronephrotic kidney is highly sensitive to vasodilatation by PTH and PTHRP, which, in addition, may constrict efferent arterioles by stimulating renin release.(ABSTRACT TRUNCATED AT 250 WORDS)

Full text

PDF

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Brenner B. M., Schor N., Ichikawa I. Role of angiotensin II in the physiologic regulation of glomerular filtration. Am J Cardiol. 1982 Apr 21;49(6):1430–1433. doi: 10.1016/0002-9149(82)90356-3. [DOI] [PubMed] [Google Scholar]
  2. Crass M. F., 3rd, Jayaseelan C. L., Darter T. C. Effects of parathyroid hormone on blood flow in different regional circulations. Am J Physiol. 1987 Oct;253(4 Pt 2):R634–R639. doi: 10.1152/ajpregu.1987.253.4.R634. [DOI] [PubMed] [Google Scholar]
  3. Dietrich M. S., Fretschner M., Nobiling R., Persson P. B., Steinhausen M. Renovascular effects of neuropeptide-Y in the split hydronephrotic rat kidney: non-uniform pattern of vascular reactivity. J Physiol. 1991 Dec;444:303–315. doi: 10.1113/jphysiol.1991.sp018879. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Edwards R. M. Segmental effects of norepinephrine and angiotensin II on isolated renal microvessels. Am J Physiol. 1983 May;244(5):F526–F534. doi: 10.1152/ajprenal.1983.244.5.F526. [DOI] [PubMed] [Google Scholar]
  5. Gaehtgens P., Benner K. U., Schickendantz S., Albrecht K. H. Method for simultaneous determination of red cell and plasma flow velocity in vitro and in vivo. Pflugers Arch. 1976 Jan 30;361(2):191–195. doi: 10.1007/BF00583465. [DOI] [PubMed] [Google Scholar]
  6. Godsall J. W., Burtis W. J., Insogna K. L., Broadus A. E., Stewart A. F. Nephrogenous cyclic AMP, adenylate cyclase-stimulating activity, and the humoral hypercalcemia of malignancy. Recent Prog Horm Res. 1986;42:705–750. doi: 10.1016/b978-0-12-571142-5.50021-5. [DOI] [PubMed] [Google Scholar]
  7. Gulbins E., Hoffend J., Zou A. P., Dietrich M. S., Schlottmann K., Cavarape A., Steinhausen M. Endothelin and endothelium-derived relaxing factor control of basal renovascular tone in hydronephrotic rat kidneys. J Physiol. 1993 Sep;469:571–582. doi: 10.1113/jphysiol.1993.sp019830. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Hecker M., Pörsti I., Bara A. T., Busse R. Potentiation by ACE inhibitors of the dilator response to bradykinin in the coronary microcirculation: interaction at the receptor level. Br J Pharmacol. 1994 Jan;111(1):238–244. doi: 10.1111/j.1476-5381.1994.tb14050.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Helwig J. J., Musso M. J., Judes C., Nickols G. A. Parathyroid hormone and calcium: interactions in the control of renin secretion in the isolated, nonfiltering rat kidney. Endocrinology. 1991 Sep;129(3):1233–1242. doi: 10.1210/endo-129-3-1233. [DOI] [PubMed] [Google Scholar]
  10. Helwig J. J., Yang M. C., Bollack C., Judes C., Pang P. K. Structure-activity relationship of parathyroid hormone: relative sensitivity of rabbit renal microvessel and tubule adenylate cyclases to oxidized PTH and PTH inhibitors. Eur J Pharmacol. 1987 Aug 21;140(3):247–257. doi: 10.1016/0014-2999(87)90281-0. [DOI] [PubMed] [Google Scholar]
  11. Hoffend J., Cavarape A., Endlich K., Steinhausen M. Influence of endothelium-derived relaxing factor on renal microvessels and pressure-dependent vasodilation. Am J Physiol. 1993 Aug;265(2 Pt 2):F285–F292. doi: 10.1152/ajprenal.1993.265.2.F285. [DOI] [PubMed] [Google Scholar]
  12. Hongo T., Kupfer J., Enomoto H., Sharifi B., Giannella-Neto D., Forrester J. S., Singer F. R., Goltzman D., Hendy G. N., Pirola C. Abundant expression of parathyroid hormone-related protein in primary rat aortic smooth muscle cells accompanies serum-induced proliferation. J Clin Invest. 1991 Dec;88(6):1841–1847. doi: 10.1172/JCI115505. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Ichikawa I., Humes H. D., Dousa T. P., Brenner B. M. Influence of parathyroid hormone on glomerular ultrafiltration in the rat. Am J Physiol. 1978 May;234(5):F393–F401. doi: 10.1152/ajprenal.1978.234.5.F393. [DOI] [PubMed] [Google Scholar]
  14. Kramer S., Reynolds F. H., Jr, Castillo M., Valenzuela D. M., Thorikay M., Sorvillo J. M. Immunological identification and distribution of parathyroid hormone-like protein polypeptides in normal and malignant tissues. Endocrinology. 1991 Apr;128(4):1927–1937. doi: 10.1210/endo-128-4-1927. [DOI] [PubMed] [Google Scholar]
  15. Mangin M., Ikeda K., Dreyer B. E., Broadus A. E. Isolation and characterization of the human parathyroid hormone-like peptide gene. Proc Natl Acad Sci U S A. 1989 Apr;86(7):2408–2412. doi: 10.1073/pnas.86.7.2408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Mok L. L., Nickols G. A., Thompson J. C., Cooper C. W. Parathyroid hormone as a smooth muscle relaxant. Endocr Rev. 1989 Nov;10(4):420–436. doi: 10.1210/edrv-10-4-420. [DOI] [PubMed] [Google Scholar]
  17. Moroi M., Akatsuka N., Fukazawa M., Hara K., Ishikawa M., Aikawa J., Namiki A., Yamaguchi T. Endothelium-dependent relaxation by angiotensin-converting enzyme inhibitors in canine femoral arteries. Am J Physiol. 1994 Feb;266(2 Pt 2):H583–H589. doi: 10.1152/ajpheart.1994.266.2.H583. [DOI] [PubMed] [Google Scholar]
  18. Musso M. J., Barthelmebs M., Imbs J. L., Plante M., Bollack C., Helwig J. J. The vasodilator action of parathyroid hormone fragments on isolated perfused rat kidney. Naunyn Schmiedebergs Arch Pharmacol. 1989 Aug;340(2):246–251. doi: 10.1007/BF00168976. [DOI] [PubMed] [Google Scholar]
  19. Musso M. J., Plante M., Judes C., Barthelmebs M., Helwig J. J. Renal vasodilatation and microvessel adenylate cyclase stimulation by synthetic parathyroid hormone-like protein fragments. Eur J Pharmacol. 1989 Dec 19;174(2-3):139–151. doi: 10.1016/0014-2999(89)90306-3. [DOI] [PubMed] [Google Scholar]
  20. Nickols G. A., Metz M. A., Cline W. H., Jr Endothelium-independent linkage of parathyroid hormone receptors of rat vascular tissue with increased adenosine 3',5'-monophosphate and relaxation of vascular smooth muscle. Endocrinology. 1986 Jul;119(1):349–356. doi: 10.1210/endo-119-1-349. [DOI] [PubMed] [Google Scholar]
  21. Nickols G. A., Nickols M. A., Helwig J. J. Binding of parathyroid hormone and parathyroid hormone-related protein to vascular smooth muscle of rabbit renal microvessels. Endocrinology. 1990 Feb;126(2):721–727. doi: 10.1210/endo-126-2-721. [DOI] [PubMed] [Google Scholar]
  22. Nobiling R., Bührle C. P., Hackenthal E., Helmchen U., Steinhausen M., Whalley A., Taugner R. Ultrastructure, renin status, contractile and electrophysiological properties of the afferent glomerular arteriole in the rat hydronephrotic kidney. Virchows Arch A Pathol Anat Histopathol. 1986;410(1):31–42. doi: 10.1007/BF00710903. [DOI] [PubMed] [Google Scholar]
  23. Pang P. K., Janssen H. F., Yee J. A. Effects of synthetic parathyroid hormone on vascular beds of dogs. Pharmacology. 1980;21(3):213–222. doi: 10.1159/000137435. [DOI] [PubMed] [Google Scholar]
  24. Pirola C. J., Wang H. M., Kamyar A., Wu S., Enomoto H., Sharifi B., Forrester J. S., Clemens T. L., Fagin J. A. Angiotensin II regulates parathyroid hormone-related protein expression in cultured rat aortic smooth muscle cells through transcriptional and post-transcriptional mechanisms. J Biol Chem. 1993 Jan 25;268(3):1987–1994. [PubMed] [Google Scholar]
  25. Roca-Cusachs A., DiPette D. J., Nickols G. A. Regional and systemic hemodynamic effects of parathyroid hormone-related protein: preservation of cardiac function and coronary and renal flow with reduced blood pressure. J Pharmacol Exp Ther. 1991 Jan;256(1):110–118. [PubMed] [Google Scholar]
  26. Saussine C., Judes C., Massfelder T., Musso M. J., Simeoni U., Hannedouche T., Helwig J. J. Stimulatory action of parathyroid hormone on renin secretion in vitro: a study using isolated rat kidney, isolated rabbit glomeruli and superfused dispersed rat juxtaglomerular cells. Clin Sci (Lond) 1993 Jan;84(1):11–19. doi: 10.1042/cs0840011. [DOI] [PubMed] [Google Scholar]
  27. Saussine C., Massfelder T., Parnin F., Judes C., Simeoni U., Helwig J. J. Renin stimulating properties of parathyroid hormone-related peptide in the isolated perfused rat kidney. Kidney Int. 1993 Oct;44(4):764–773. doi: 10.1038/ki.1993.311. [DOI] [PubMed] [Google Scholar]
  28. Simeoni U., Massfelder T., Saussine C., Judes C., Geisert J., Helwig J. J. Involvement of nitric oxide in the vasodilatory response to parathyroid hormone-related peptide in the isolated rabbit kidney. Clin Sci (Lond) 1994 Mar;86(3):245–249. doi: 10.1042/cs0860245. [DOI] [PubMed] [Google Scholar]
  29. Steinhausen M., Blum M., Fleming J. T., Holz F. G., Parekh N., Wiegman D. L. Visualization of renal autoregulation in the split hydronephrotic kidney of rats. Kidney Int. 1989 May;35(5):1151–1160. doi: 10.1038/ki.1989.104. [DOI] [PubMed] [Google Scholar]
  30. Steinhausen M., Endlich K., Wiegman D. L. Glomerular blood flow. Kidney Int. 1990 Nov;38(5):769–784. doi: 10.1038/ki.1990.271. [DOI] [PubMed] [Google Scholar]
  31. Steinhausen M., Snoei H., Parekh N., Baker R., Johnson P. C. Hydronephrosis: a new method to visualize vas afferens, efferens, and glomerular network. Kidney Int. 1983 Jun;23(6):794–806. doi: 10.1038/ki.1983.98. [DOI] [PubMed] [Google Scholar]
  32. Strewler G. J., Stern P. H., Jacobs J. W., Eveloff J., Klein R. F., Leung S. C., Rosenblatt M., Nissenson R. A. Parathyroid hormonelike protein from human renal carcinoma cells. Structural and functional homology with parathyroid hormone. J Clin Invest. 1987 Dec;80(6):1803–1807. doi: 10.1172/JCI113275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Thiede M. A., Daifotis A. G., Weir E. C., Brines M. L., Burtis W. J., Ikeda K., Dreyer B. E., Garfield R. E., Broadus A. E. Intrauterine occupancy controls expression of the parathyroid hormone-related peptide gene in preterm rat myometrium. Proc Natl Acad Sci U S A. 1990 Sep;87(18):6969–6973. doi: 10.1073/pnas.87.18.6969. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Trizna W., Edwards R. M. Relaxation of renal arterioles by parathyroid hormone and parathyroid hormone-related protein. Pharmacology. 1991;42(2):91–96. doi: 10.1159/000138778. [DOI] [PubMed] [Google Scholar]
  35. Wayland H., Johnson P. C. Erythrocyte velocity measurement in microvessels by a two-slit photometric method. J Appl Physiol. 1967 Feb;22(2):333–337. doi: 10.1152/jappl.1967.22.2.333. [DOI] [PubMed] [Google Scholar]
  36. Winquist R. J., Baskin E. P., Vlasuk G. P. Synthetic tumor-derived human hypercalcemic factor exhibits parathyroid hormone-like vasorelaxation in renal arteries. Biochem Biophys Res Commun. 1987 Nov 30;149(1):227–232. doi: 10.1016/0006-291x(87)91628-7. [DOI] [PubMed] [Google Scholar]

Articles from The Journal of Physiology are provided here courtesy of The Physiological Society

RESOURCES