Tubulovascular nitric oxide crosstalk: Buffering of angiotensin II-induced medullary vasoconstriction

Jeffrey G. Dickhout, Takefumi Mori, Allen W. Cowley

Research output: Contribution to journalArticlepeer-review

88 Citations (Scopus)

Abstract

Studies were designed to determine the source of NO responsible for buffering of the angiotensin II (Ang II)-mediated decrease of blood flow in the renal medulla. Intracellular Ca2+ concentration ([Ca2+]i) and NO production ([NO]i) of pericytes and endothelium of the vasa recta were independently measured with the use of fura 2-AM and 4,5-diaminofluorescein diacetate (DAF-2DA), respectively, in microtissue strips of the vascular bundles of the outer medullary vasa recta. Disruption of the endothelium of the vasa recta by perfusion with latex microspheres enabled imaging of the pericytes. Ang II (1 μmol/L) produced an increase of [NO]i of 19±6 U in pericytes of the vasa recta when the vessels were adjacent to medullary thick ascending limbs (mTALs). Pericytes of isolated vasa recta without surrounding mTALs showed a rapid peak increase in [Ca2+]i of 248±107 nmol/L, with a sustained elevation of 107±75 nmol/L, but did not show an increase in [NO]i to either Ang II (1 μmol/L) or the Ca2+ ionophore 4-bromo-A23187 (5 μmol/L). These observations indicated the lack of Ang II and Ca2+-sensitive NO production in pericytes of the vasa recta. In isolated vasa recta with intact endothelium, Ang II reduced [Ca2+]i from 128±28 to 62±13 nmol/L and failed to increase [NO]i. However, the Ca2+ ionophore did increase [NO]i in the endothelium (47±8 U), indicating the presence of Ca2+-sensitive NO production. Significant increases of [NO]i were observed in single isolated mTALs in response to both Ang II (33±6 U) and the Ca2+ ionophore (51±18 U). We conclude that Ang II increases [Ca2+]i in pericytes of the descending vasa recta as part of its constrictor action and that this vasoconstriction is buffered by the NO from the surrounding tubular elements, such as mTALs.

Original languageEnglish
Pages (from-to)487-493
Number of pages7
JournalCirculation research
Volume91
Issue number6
DOIs
Publication statusPublished - 2002 Sep 20

Keywords

  • Endothelium
  • Intracellular Ca
  • Nitric oxide
  • Pericytes
  • Vasa recta

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

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