April 10, 2007Circulation
Compartmentalization of Cardiac β-Adrenergic Inotropy Modulation by Phosphodiesterase Type 5
Key result
Sildenafil suppressed isoproterenol-stimulated contractility via protein kinase G activation, whereas atrial natriuretic peptide had no effect despite increasing cGMP nearly 5-fold.
Population
Intact C57/BL6 mouse hearts and adult isolated myocytes
Comparison
PDE-5 inhibition with 0.1 to 1 micromol/L… vs 10 micromol/L atrial natriuretic peptide…
Design
Preclinical
Authors
Discussion
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Implication
Preclinical compartmentalization of cGMP effects may guide selective PDE5 targeting; leaves open human relevance and therapeutic translation.
Structured PICO
P
Population
Intact C57/BL6 mouse hearts and adult isolated myocytes
I
Intervention
PDE-5 inhibition with 0.1 to 1 micromol/L sildenafil (SIL) combined with isoproterenol (ISO)
C
Comparator
10 micromol/L atrial natriuretic peptide (ANP) combined with isoproterenol (ISO)
O
Outcome
Beta-adrenergic modulation (contractility), myocardial cGMP levels, and protein kinase G activationsurrogate
Cardiac beta-adrenergic response regulation by cGMP is compartmentalized and specifically linked to a nitric oxide-synthesis/PDE-5-hydrolyzed pool signaling via protein kinase G, rather than natriuretic peptide-stimulated cGMP.
Cite This Study
Takimoto et al. (2007) studied this question. Sildenafil vs. Atrial natriuretic peptide (ANP) was evaluated on Isoproterenol-stimulated contractility. Sildenafil suppressed isoproterenol-stimulated contractility via protein kinase G activation, whereas atrial natriuretic peptide had no effect despite increasing cGMP nearly 5-fold.