Atrial Natriuretic Peptide–Mediated Inhibition of Microcirculatory Endothelial Ca ²⁺ and Permeability Response to Histamine Involves cGMP-Dependent Protein Kinase I and TRPC6 Channels
Key result
Atrial natriuretic peptide attenuates histamine-induced microvascular leakage via endothelial GC-A/cGMP/cGKI signaling and inhibitory phosphorylation of TRPC6 channels.
Population
Mouse cremaster microcirculation and cultured microvascular human dermal endothelial cells
Comparison
Atrial natriuretic peptide, sildenafil… vs Control/vehicle or genetic knockout models
Design
Preclinical
Authors
Discussion
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Member takes
Implication
Hypothesis-generating for cGMP pathway modulation in permeability disorders; human studies required before clinical consideration.
Structured PICO
P
Population
Mouse cremaster microcirculation (wild-type, endothelial-restricted GC-A or cGKI knockout, TRPC6 knockout) and cultured microvascular human dermal endothelial cells
I
Intervention
Atrial natriuretic peptide (ANP), sildenafil, hyperforin, SKF96365
C
Comparator
Control/vehicle or genetic knockout models
O
Outcome
Microvascular endothelial leakage (extravasation of fluorescent dextran) and endothelial intracellular calcium concentrationsurrogate
ANP attenuates histamine-induced microvascular leakage via endothelial GC-A/cGMP/cGKI signaling and inhibitory phosphorylation of TRPC6 channels, a pathway that can be enhanced by sildenafil.
Cite This Study
Chen et al. (2013) studied Microvascular endothelial leakage. Atrial natriuretic peptide (ANP) vs. Control / Knockout models was evaluated on Histamine-provoked vascular leakage and endothelial [Ca(2+)]i. Atrial natriuretic peptide attenuates histamine-induced microvascular leakage via endothelial GC-A/cGMP/cGKI signaling and inhibitory phosphorylation of TRPC6 channels.