Copyright © 2004, European Society of Cardiology
Intact nitric oxide production is obligatory for the sustained flow response during hypercapnic acidosis in guinea pig heart
aDepartment of Anesthesiology and Intensive Care Medicine, Medical Faculty Carl Gustav Carus, University Hospital Dresden, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany
bInstitute of Physiology, Medical Faculty Carl Gustav Carus, TU Dresden, Fetscherstr. 74, 01307 Dresden, Germany
* Corresponding author. Tel.: +49 351 4586006; fax: +49 351 4586301. Email address: Anke.Heintz{at}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 pCO2 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 pCO2. In CP perfused hearts L-NAME (100 µmol/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.
KEYWORDS Hypercapnia; Acidosis; Coronary circulation; Nitric oxide; K+ATP channel; Vasoconstriction/dilation
Time for primary review 12 days
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  G. E. Foster, J. V. Brugniaux, V. Pialoux, C. T. C. Duggan, P. J. Hanly, S. B. Ahmed, and M. J. Poulin Cardiovascular and cerebrovascular responses to acute hypoxia following exposure to intermittent hypoxia in healthy humans J. Physiol., July 1, 2009; 587(13): 3287 - 3299. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Momen, V. Mascarenhas, A. Gahremanpour, Z. Gao, R. Moradkhan, A. Kunselman, J. P. Boehmer, L. I. Sinoway, and U. A. Leuenberger Coronary blood flow responses to physiological stress in humans Am J Physiol Heart Circ Physiol, March 1, 2009; 296(3): H854 - H861. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. Heintz, M. Damm, M. Brand, T. Koch, and A. Deussen Coronary flow regulation in mouse heart during hypercapnic acidosis: role of NO and its compensation during eNOS impairment Cardiovasc Res, January 1, 2008; 77(1): 188 - 196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Cevese Coronary circulation: Nitric oxide and hypercapnic acidosis Cardiovasc Res, April 1, 2005; 66(1): 7 - 8. [Full Text] [PDF]
|
|