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Isolation of Intrapulmonary Artery and Smooth Muscle Cells to Investigate Vascular Responses
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Angiotensin IV-mediated pulmonary artery vasorelaxation is due to endothelial intracellular calcium release

S Chen1, J M Patel, E R Block

  • 1Department of Medicine, University of Florida College of Medicine, Gainesville, Florida 32608, USA.

American Journal of Physiology. Lung Cellular and Molecular Physiology
|October 29, 2000
PubMed

Insights

Angiotensin IV triggers vasodilation in pulmonary arteries by acting on endothelial cells, not smooth muscle cells. This process involves calcium release and specific signaling pathways, highlighting its endothelium-dependent nature.

Area of Science:

  • Cardiovascular Physiology
  • Endothelial Cell Biology
  • Vascular Pharmacology

Background:

  • Pulmonary artery (PA) smooth muscle cells (PASMCs) and endothelial cells (PAECs) play critical roles in regulating vascular tone.
  • Angiotensin (ANG) IV is a peptide with known roles in the cardiovascular system, but its specific mechanisms in pulmonary arteries require elucidation.
  • Understanding the signaling pathways involved in ANG IV-mediated vascular effects is crucial for potential therapeutic interventions.

Purpose of the Study:

  • To investigate the role of Angiotensin IV in regulating pulmonary artery vasodilation.
  • To determine the specific cell types and signaling mechanisms involved in ANG IV's vascular effects.
  • To elucidate the contribution of intracellular calcium ([Ca(2+)](i)) release and associated pathways in ANG IV-mediated responses.

Main Methods:

  • Measurement of cyclic guanosine monophosphate (cGMP) production in PAECs and PASMCs following ANG IV stimulation.
  • Assessment of ANG IV-induced vasodilation in endothelium-intact and endothelium-denuded pulmonary arteries using pharmacological agents and antagonists.
  • Investigation of intracellular calcium ([Ca(2+)](i)) dynamics in PAECs using inhibitors of G protein, phospholipase C, and phosphoinositide 3-kinase (PI 3-kinase).

Main Results:

  • ANG IV significantly increased cGMP production in PASMCs, mediated by PAECs, not directly in PASMCs.
  • ANG IV induced dose-dependent vasodilation in intact pulmonary arteries, blocked by ANG IV receptor antagonists, indicating an endothelium-dependent mechanism.
  • ANG IV-mediated [Ca(2+)](i) release in PAECs involved G protein-coupled receptors, phospholipase C, PI 3-kinase, and ryanodine-sensitive stores, crucial for vasodilation.

Conclusions:

  • Angiotensin IV-mediated vasodilation of pulmonary arteries is an endothelium-dependent process.
  • The signaling cascade involves ANG IV receptor activation on PAECs, leading to [Ca(2+)](i) release via G protein-phospholipase C-PI 3-kinase pathways.
  • These findings reveal a novel mechanism of ANG IV action in the pulmonary vasculature, distinct from direct effects on smooth muscle cells.

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