Key result
Increased endogenous cAMP potentiates NO/cGMP-induced arteriolar relaxation when MRP5 expression is normal, as the reduction of cGMP efflux predominates over cAMP stimulation of cGMP hydrolysis.
Population
Male rats (anesthetized in vivo model)
Comparison
cAMP elevation via forskolin, with or without… vs Control rats treated with missense ODN
Design
Preclinical
Authors
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Warrants no change in clinical practice; leaves open MRP5 modulation of cerebral NO signaling for future study.
Effect estimate: 35-50% lower maximal response in MRP5 knockdown
In vivo, cAMP potentiates NO/cGMP-induced cerebral arteriolar relaxation primarily by reducing cGMP efflux via MRP5, which predominates over its opposing effect of stimulating cGMP hydrolysis via PDE5.
Xu et al. (2004) studied Cerebral vasodilation. cAMP elevation via forskolin, MRP5 knockdown, and PDE5 inhibition vs. Control (missense ODN treated) rats was evaluated on Pial arteriolar diameter changes (SNAP-induced dilations) (35-50% lower maximal response in MRP5 knockdown). Increased endogenous cAMP potentiates NO/cGMP-induced arteriolar relaxation when MRP5 expression is normal, as the reduction of cGMP efflux predominates over cAMP stimulation of cGMP hydrolysis.