Endothelin Antagonism Uncovers Insulin-Mediated Vasorelaxation In Vitro and In Vivo
Key result
Endothelin receptor blockade with bosentan uncovered insulin-mediated vasorelaxation in rat aortas, reducing maximum contraction to norepinephrine (74% vs 92% with bosentan alone, P<0.002).
Why the study?
Does endothelin antagonism uncover insulin-mediated vasorelaxation in rat aortas?
Population
Rat aortas (in vitro and in vivo models)
Comparison
Subthreshold concentrations of insulin combined… vs Bosentan alone, insulin alone
Design
Preclinical
Follow-up
3 weeks (for long-term treatment)
Authors
Discussion
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Member takes
Implication
Hypothesis-generating in rat aortas; leaves open any role for endothelin antagonism in human insulin-mediated vascular function.
Structured PICO
Does endothelin antagonism uncover insulin-mediated vasorelaxation in rat aortas?
P
Population
Rat aortas (in vitro and in vivo models)
I
Intervention
Subthreshold concentrations of insulin (100 mU/L) combined with short-term endothelin A/B receptor blockade (bosentan 10(-2) mmol/L or BQ-123) or long-term bosentan treatment (100 mg/kg/d for 3 weeks)
C
Comparator
Bosentan alone, insulin alone
O
Outcome
Norepinephrine-induced contraction (percent maximum contraction and sensitivity)surrogate
Main Result
Absolute Event Rate: 74% vs 92%
p-value: p=<0.002
Endothelin receptor blockade uncovers insulin-mediated vasorelaxation in rat aortas, demonstrating a functional interaction between insulin, endothelin-1, and tetrahydrobiopterin in modulating vascular tone.
Cite This Study
Verma et al. (2001) studied this question. Bosentan and insulin vs. Bosentan alone or insulin alone was evaluated on Percent maximum contraction to norepinephrine (p=<0.002). Endothelin receptor blockade with bosentan uncovered insulin-mediated vasorelaxation in rat aortas, reducing maximum contraction to norepinephrine (74% vs 92% with bosentan alone, P<0.002).