Endothelin-1 Stimulates the Na + /Ca 2+ Exchanger Reverse Mode Through Intracellular Na + (Na + i )–Dependent and Na + i -Independent Pathways
Key result
Endothelin-1 induces a positive inotropic effect through a mandatory NHE-mediated increase in intracellular Na+, with an additional Na+-independent, PKC-dependent stimulation of the Na+/Ca2+ exchanger.
Population
Cat papillary muscles and isolated cat ventricular myocytes
Comparison
Endothelin-1 (ET-1) 5 nmol/L vs Low extracellular K+ (K+o) or baseline conditions
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Should not alter clinical contractility management; leaves open translation of ET-1/NHE/PKC mechanisms to human HF.
Structured PICO
P
Population
Cat papillary muscles and isolated cat ventricular myocytes
I
Intervention
Endothelin-1 (ET-1) 5 nmol/L
C
Comparator
Low extracellular K+ (K+o) or baseline conditions
O
Outcome
Positive inotropic effect (PIE), intracellular Na+ concentration (Na+i), and Na+/Ca2+ exchanger (NCX) currentsurrogate
Endothelin-1 enhances cardiac contractility through both an NHE-mediated increase in intracellular sodium driving reverse-mode NCX and a direct PKC-dependent stimulation of NCX.
Cite This Study
Aiello et al. (2004) studied this question. Endothelin-1 (ET-1) was evaluated on Positive inotropic effect (PIE) and intracellular Na+ concentration. Endothelin-1 induces a positive inotropic effect through a mandatory NHE-mediated increase in intracellular Na+, with an additional Na+-independent, PKC-dependent stimulation of the Na+/Ca2+ exchanger.