title: Intact nitric oxide production is obligatory for the sustained flow response during hypercapnic acidosis in guinea pig heart.
abstract: 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.
  
  
  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.
authors.affiliation: Department 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
authors.forename: Anke
authors.initials: A
authors.lastname: Heintz
authors.forename: Thea
authors.initials: T
authors.lastname: Koch
authors.forename: Andreas
authors.initials: A
authors.lastname: Deussen
mesh_terms: D000138:Acidosis / Q000378:metabolism / Q000503:physiopathology*; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects; D004730:Endothelium, Vascular / Q000378:metabolism*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D006168:Guinea Pigs; D006935:Hypercapnia / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000378:metabolism*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010101:Oxygen Consumption; D010477:Perfusion; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000378:metabolism; D013997:Time Factors; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology; D019323:omega-N-Methylarginine / Q000494:pharmacology
chemical_list: D026902:Potassium Channel Blockers; D015221:Potassium Channels; D019323:omega-N-Methylarginine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester