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Updated: Aug 19, 2026
Analytical Techniques for Assaying Nitric Oxide Bioactivity
Published on: June 18, 2012
Intact nitric oxide production is obligatory for the sustained flow response during hypercapnic acidosis in guinea
Anke Heintz1, Thea Koch, Andreas Deussen
1Department of Anesthesiology and Intensive Care Medicine, Medical Faculty Carl Gustav Carus, University Hospital Dresden, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany. Anke.Heintz@mailbox.tu-dresden.de
Objective:
The mechanisms underlying hypercapnic coronary dilation remain unsettled. This study tests the hypothesis that flow dependent NO production is obligatory for the hypercapnic flow response.
Methods/Results:
In isolated, constant pressure (CP) perfused guinea pig hearts a step change of arterial pCO(2) from 38.6 to 61.4 mm Hg induced a bi-phasic flow response with an early transient (maximum 60 s) and a consecutive persisting flow rise (121.6+/-6.6 (S.D.) % after 10 min). In contrast, when perfused with constant flow (CF), perfusion pressure only transiently (2 min) fell by 7.4+/-4.8 % following the step change of arterial pCO(2). In CP perfused hearts L-NAME (100 micromol/l) specifically abolished the delayed flow rise during hypercapnic acidosis (102.37+/-2.9% after 10 min), whereas the inhibitor had no effect on perfusion pressure response in CF perfused hearts. Under CP perfusion arterial hypercapnia resulted in a transient rise of coronary cGMP release (from 0.69+/-0.35 to 1.12+/-0.68 pmol/ml), which was abolished after L-NAME. Surprisingly, the K(+)ATP channel blocker glibenclamide did not have any significant effect on the hypercapnic flow response but largely blunted reactive hyperemia after a 20 s flow stop.
Conclusions:
The delayed steady state hypercapnic flow response in guinea pig heart requires intact NO production. The absence of a persisting decrease in coronary resistance under CF perfusion points to an important role of shear stress dependent NO production.
