October 1, 2000AJP Heart and Circulatory Physiology
cGMP-independent inotropic effects of nitric oxide and peroxynitrite donors: potential role for nitrosylation
Key result
Infusion of the peroxynitrite donor SIN-1 increased the rate of left ventricular pressure rise by 19% (P<0.001) without increasing cGMP, suggesting a cGMP-independent inotropic mechanism.
Why the study?
Do nitric oxide and peroxynitrite donors stimulate myocardial contractility via a cGMP-independent mechanism in isolated rat hearts?
Population
Isolated rat hearts and in vivo mice
Design
Preclinical
Authors
Discussion
Loading...
Member takes
Implication
No immediate clinical implications from isolated hearts; leaves open non-cGMP inotropic pathways for in vivo validation.
Structured PICO
Do nitric oxide and peroxynitrite donors stimulate myocardial contractility via a cGMP-independent mechanism in isolated rat hearts?
P
Population
Isolated rat hearts and in vivo mice used to test the inotropic effects of nitric oxide and peroxynitrite donors.
I
Intervention
Infusion of nitric oxide donors including 3-morpholinosydnonimine (SIN-1, 10(-5) M), sodium nitroprusside (10(-10)-10(-7) M), or diethylamine/NO (DEA/NO; 10(-7) M), with or without superoxide dismutase (SOD; 150 U/ml), guanylyl cyclase inhibitor, or glutathione
O
Outcome
Rate of left ventricular pressure rise (+dP/dt) and effluent cGMP or cAMP levelssurrogate
Main Result
p-value: p=<0.001
Peroxynitrite and NO donors can stimulate myocardial contractility independently of guanylyl cyclase activation, suggesting a role for S-nitrosylation in positive inotropic effects.
Cite This Study
Paolocci et al. (2000) studied Myocardial contractility (animal model). Nitric oxide and peroxynitrite donors (SIN-1, DEA/NO) vs. Baseline / inhibitors (SOD, glutathione, 1H-(1,2,4)oxadiazolo-(4,3,-a)quinoxalin-1-one) was evaluated on Rate of left ventricular pressure rise (+dP/dt) (p=<0.001). Infusion of the peroxynitrite donor SIN-1 increased the rate of left ventricular pressure rise by 19% (P<0.001) without increasing cGMP, suggesting a cGMP-independent inotropic mechanism.