Abstract
Objective: The mechanism by which remote microvascular preconditioning (RMP) response is initiated was recently reported (Am J Physiol 290:H264, 2006). The goal of this study was to further characterize RMP and to investigate the extent to which RMP altered local vasoactive responses.
Methods: Arteriolar networks were examined in the cheek pouch of anesthetized (pentobarbital, 70 mg/kg) hamsters (n = 143). RMP was initiated with nitroprusside (SNP) or adenosine (ADO) via micropipette to a downstream arteriole or via tissue bath. Upstream (∼ 800 μ m), at the entrance to the network, local vasoactive responses were obtained with local micropipette application.
Results: The RMP response requires 10 to 15 min to manifest, and cycles down with > 5 upstream challenges (local exposures). Without challenge, the response does not cycle down over 8 h. RMP results in enhanced dilation to SNP and attenuated dilation to ADO. SNP can initiate RMP with micropipette exposure to the local downstream arteriolar segment. ADO only initiates RMP with tissue bath exposure, but at low concentrations (10−8 M). RMP causes a shift in phosphodiesterase (PDE) maintenance of tone, as seen by using PDE inhibitors. This involves a shift from PDE4 to PDE3, and does not appear to affect PDE1 or PDE5.
Conclusions: These findings are consistent with RMP inducing a fundamental shift from cAMP and towards cGMP maintenance of dilatory tone.
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This work was supported by NIH grant HL55492 (to M.F.).