Vasorelaxant properties of parathyroid hormone-related protein in the mouse: Evidence for endothelium involvement independent of nitric oxide formation

Roy L. Sutliff, Craig S. Weber, Jin Qian, Marion L. Miller, Thomas L. Clemens, Richard J. Paul

Research output: Contribution to journalArticlepeer-review

Abstract

PTH-related peptide is produced in vascular smooth muscle and is believed to participate in the local control of vascular tone. The recent identification of mid-region PTHrP peptides, as well as the discovery of multiple receptors in blood vessels, rinses new questions concerning the mechanisms by which PTHrP relaxes the vasculature. In this study, we examined these mechanisms in two vascular beds of the mouse. PTHrP-(1-34) and PTH-(1-34), but not PTHrP-(38-64) or PTHrP-(38-94), caused concentration-dependent relaxation of pre-contracted aortas and reduced the spontaneous phasic activity of the portal vein. PTHrP and PTH-induced aortic relaxations were largely endothelium dependent, whereas an intact endothelium was not necessary for maximal portal vein relaxation. The endothelium-dependent component of PTHrP and PTH-induced aortic relaxations were unaffected by pretreatment with either L-NNA or indomethacin but were abolished by pretreatment with tetrabutyl ammonium. These results demonstrate that the N-terminal portions of PTHrP and PTH are required for their vasorelaxant activity in the mouse. In addition, maximal relaxant activity of PTHrP and PTH in routine aorta is dependent on the endothelium, which appears to involve the generation of an endothelium-derived hyperpolarizing factor.

Original languageEnglish (US)
Pages (from-to)2077-2083
Number of pages7
JournalEndocrinology
Volume140
Issue number5
DOIs
StatePublished - 1999
Externally publishedYes

ASJC Scopus subject areas

  • Endocrinology

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