title: Adaptation of myocardial blood flow to increased metabolic demand is not dependent on endothelial vasodilators in the rat heart.
abstract: OBJECTIVE
  To investigate the role of endothelial vasodilating factors in adaptation of myocardial blood flow to increased metabolic demands.
  
  
  METHODS
  Alterations in the effects of endothelium dependent (acetylcholine) and independent (sodium nitroprusside) vasodilators and the beta 1 receptor agonist dobutamine were studied after inhibition of endothelium derived relaxing factor (EDRF) with L-NG-nitro-arginine methyl ester (L-NAME), prostanoid synthesis with indomethacin, and ATP sensitive potassium channels with glibenclamide.
  
  
  METHODS
  Female Wistar rats, in situ perfused heart.
  
  
  METHODS
  Myocardial blood flow (H2 clearance); systolic fractional thickening (pulsed Doppler); mean arterial blood pressure.
  
  
  RESULTS
  L-NAME reduced myocardial blood flow by 58 (12)% (mean (SD), P < 0.001) and systolic thickening fraction (FT) by 36 (9)% (P < 0.05). These effects were significantly reversed by administration of L-arginine but not D-arginine. Pretreatment with L-NAME inhibited the increase in myocardial blood flow caused by acetylcholine (control: +42 (9)%; L-NAME: -29 (7)%, P < 0.001) but did not affect the increase in myocardial blood flow caused by sodium nitroprusside (control: +44 (5)%; L-NAME: +34 (10)%, NS). Pretreatment with L-NAME did not change the effect of dobutamine on myocardial blood flow (+61 (3)%) and FT (+32 (8)%) compared with baseline values (P < 0.001). Neither pretreatment with indomethacin nor with glibenclamide reduced the dobutamine induced increase in myocardial blood flow.
  
  
  CONCLUSIONS
  Inhibition of EDRF, prostanoid synthesis, and ATP sensitive potassium channels did not reduce the vasodilator reserve during increased metabolic demands induced by beta 1 adrenergic stimulation. Therefore, adaptation of myocardial blood flow to increased metabolic demands is independent of endothelial relaxing factors in the rat heart.
authors.affiliation: Department of Cardiology, University of Heidelberg, Germany.
authors.forename: C P
authors.initials: CP
authors.lastname: Tiefenbacher
authors.forename: H
authors.initials: H
authors.lastname: Tillmanns
authors.forename: F
authors.initials: F
authors.lastname: Niroomand
authors.forename: R
authors.initials: R
authors.lastname: Zimmermann
authors.forename: W
authors.initials: W
authors.lastname: Kübler
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000222:Adaptation, Physiological; D058665:Adrenergic beta-1 Receptor Agonists; D000818:Animals; D003326:Coronary Circulation / Q000187:drug effects*; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004280:Dobutamine / Q000494:pharmacology*; D005260:Female; D005905:Glyburide / Q000494:pharmacology; D007213:Indomethacin / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D009599:Nitroprusside / Q000494:pharmacology; D010477:Perfusion; D015221:Potassium Channels / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D058665:Adrenergic beta-1 Receptor Agonists; D016861:Cyclooxygenase Inhibitors; D015221:Potassium Channels; D014665:Vasodilator Agents; D009599:Nitroprusside; D009569:Nitric Oxide; D004280:Dobutamine; D000109:Acetylcholine; D005905:Glyburide; D019331:NG-Nitroarginine Methyl Ester; D007213:Indomethacin