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January 1, 1988Pharmacology & Toxicology

Influence of Endothelium on the Response to Calcium Agonists, Calcium, Potassium and Noradrenaline in Rat Aorta

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Population

Isolated thoracic aorta from rats

Comparison

Removal of endothelium and exposure to calcium… vs Aortic preparations with intact endothelium

Design

Preclinical

Authors

EMErich O. MikkelsenAarhus UniversityGCGonzalo CostaUniversidad de la República de UruguayNNNiels C. Berg NyborgNovo Nordisk (Denmark)

Discussion

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Overview

Endothelium-derived modulation of contractility in rat aorta warrants consideration in vascular experiments; leaves open translation to human disease or therapy.

Key Points

  • To determine how intact endothelium influences vascular contractile and relaxant responses to calcium channel agonists, potassium, noradrenaline, and calcium in rat thoracic aorta.
  • Evaluated isolated rat thoracic aortic rings with intact and denuded endothelium under exposure to BAY K 8644, CGP 28392, potassium, noradrenaline, and extracellular calcium.
  • Assessed concentration-dependent contractile responses (10⁻⁹–10⁻⁵ M) and relaxation in potassium-precontracted vessels at higher agonist concentrations (10⁻⁴ M).
  • Endothelial removal enhanced contractile responses to both BAY K 8644 and CGP 28392, while maintaining the higher relative contractile efficacy of BAY K 8644 over CGP 28392.
  • Endothelial denudation caused a leftward potency shift in concentration-response curves for potassium and noradrenaline without altering maximal contraction.
  • Vessel relaxation at high agonist concentrations (10⁻⁴ M) and calcium-induced contractions in activated rings were unaffected by the absence of endothelium.

Structured PICO

P
Population
Isolated thoracic aorta from rats
I
Intervention
Removal of endothelium and exposure to calcium agonists (BAY K 8644, CGP 28392), potassium, noradrenaline, and calcium
C
Comparator
Aortic preparations with intact endothelium
O
Outcome
Contractile and relaxant responses to the applied substancessurrogate

Endothelium-derived factors depress the contractile response to calcium agonists, potassium, and noradrenaline in rat aorta, likely by influencing smooth muscle cell membrane potential.

Cite This Study

Mikkelsen et al. (1988) studied this question.

synapsesocial.com/papers/6a87d7916841b83273ad2f95https://doi.org/10.1111/j.1600-0773.1988.tb01838.x
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Also Consider

Synapse has enriched 4 closely related papers on similar clinical questions. Consider them for comparative context:

  1. 1Calcium Channel Activation Does Not Increase Release of Endothelial-Derived Relaxant Factors (EDRF) in Rat Aorta Although Tonic Release of EDRF May Modulate Calcium Channel Activity in Smooth Muscle1986 · 53 citations
  2. 2Calcium channel activation in vascular smooth muscle by BAY K 86441984 · 108 citations
  3. 3Synthetic atrial peptide inhibits intracellular calcium release in smooth muscle1986 · 74 citations
  4. 4Stimulation rate modulates effects of the dihydropyridine CGP 28 392 on cardiac calcium‐dependent action potentials1985 · 6 citations