Increased vascular contractility in hypertension results from impaired endothelial calcium signaling

Research output: Contribution to journalArticlepeer-review

50 Citations (Scopus)
45 Downloads (Pure)

Abstract

Endothelial cells line all blood vessels and are critical regulators of vascular tone. In hypertension, disruption of endothelial function alters the release of endothelial-derived vasoactive factors and results in increased vascular tone. Although the release of endothelial-derived vasodilators occurs in a Ca2+-dependent manner, little is known on how Ca2+ signaling is altered in hypertension. A key element to endothelial control of vascular tone is Ca2+ signals at specialized regions (myoendothelial projections) that connect endothelial cells and smooth muscle cells. This work describes disruption in the operation of this key Ca2+ signaling pathway in hypertension. We show that vascular reactivity to phenylephrine is increased in hypertensive (spontaneously hypertensive rat) when compared with normotensive (Wistar Kyoto) rats. Basal endothelial Ca2+ activity limits vascular contraction, but that Ca2+-dependent control is impaired in hypertension. When changes in endothelial Ca2+ levels are buffered, vascular contraction to phenylephrine increased, resulting in similar responses in normotension and hypertension. Local endothelial IP3(inositol trisphosphate)-mediated Ca2+ signals are smaller in amplitude, shorter in duration, occur less frequently, and arise from fewer sites in hypertension. Spatial control of endothelial Ca2+ signaling is also disrupted in hypertension: local Ca2+ signals occur further from myoendothelial projections in hypertension. The results demonstrate that the organization of local Ca2+ signaling circuits occurring at myoendothelial projections is disrupted in hypertension, giving rise to increased contractile responses.

Original languageEnglish
Pages (from-to)1200-1214
Number of pages15
JournalHypertension
Volume74
Issue number5
Early online date23 Sept 2019
DOIs
Publication statusPublished - 1 Nov 2019

Keywords

  • blood pressure
  • calcium
  • endothelial cells
  • hypertension
  • phenylephrine

Fingerprint

Dive into the research topics of 'Increased vascular contractility in hypertension results from impaired endothelial calcium signaling'. Together they form a unique fingerprint.

Cite this