Activation of nitric oxide synthase by β2‐adrenoceptors in human umbilical vein endothelium in vitro
Why the study?
Does beta2-adrenergic stimulation increase nitric oxide generation and vasorelaxation in human umbilical vein endothelium?
Population
Human umbilical vein rings and cultured human umbilical vein endothelial cells (HUVEC)
Comparison
Isoprenaline, dibutyryl cyclic AMP, and forskolin vs Basal conditions, beta-adrenergic blockade…
Design
Preclinical
Authors
Discussion
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Implication
Beta2 stimulation may enhance endothelial NO vasorelaxation; hypothesis-generating and leaves open clinical relevance beyond ex vivo models.
Key Points
- To determine whether beta-adrenoceptor stimulation in human umbilical vein endothelium promotes vasorelaxation and nitric oxide synthesis through a cyclic AMP-mediated pathway.
- Assessed vasorelaxant responses in precontracted human umbilical vein rings treated with isoprenaline or dibutyryl cyclic AMP, with or without adrenergic antagonists, endothelial denudation, and the NOS inhibitor L-NMMA.
- Quantified nitric oxide synthase activity via [3H]-L-arginine to [3H]-L-citrulline conversion and adenylyl cyclase activity via [alpha-32P]-ATP conversion in cultured human umbilical vein endothelial cells (HUVEC).
- Isoprenaline induced vasorelaxation that was abolished by beta2-blockade, endothelial removal, or 1 mM L-NMMA; dibutyryl cyclic AMP-induced vasorelaxation was also significantly suppressed by 1 mM L-NMMA (Emax reduced from 90.0 ± 9.3% to 50.5 ± 9.9%, P < 0.05).
- Isoprenaline (1 µM) significantly stimulated NOS activity in HUVEC by 34.0 ± 5.9% over basal levels (P < 0.001) and increased adenylyl cyclase activity in a concentration-dependent manner mediated specifically by beta2-adrenoceptors.
- Forskolin (1 µM) and dibutyryl cyclic AMP (1 mM) stimulated endothelial NOS activity to levels similar to 1 µM isoprenaline, and these increases were completely blocked by NOS inhibition.
Structured PICO
Does beta2-adrenergic stimulation increase nitric oxide generation and vasorelaxation in human umbilical vein endothelium?
P
Population
Human umbilical vein rings and cultured human umbilical vein endothelial cells (HUVEC)
I
Intervention
Isoprenaline (nonselective beta-adrenergic agonist), dibutyryl cyclic AMP, and forskolin
C
Comparator
Basal conditions, beta-adrenergic blockade, endothelium removal, or NOS inhibitor (L-NMMA)
O
Outcome
Vasorelaxation and nitric oxide synthase (NOS) activitysurrogate
Endothelial beta2-adrenergic stimulation and cyclic AMP elevation activate the L-arginine/NO system, causing vasorelaxation in human umbilical veins.
Cite This Study
Ferro et al. (1999) studied this question.