title: Coronary blood flow responses are impaired independent of NO and endothelial function in conscious dogs with dilated cardiomyopathy.
abstract: BACKGROUND
  Dilated cardiomyopathy (DCM) is characterized by nitric oxide (NO) deficiency and endothelial dysfunction. Whether endothelium-independent vasodilation is preserved, particularly in the coronary circulation, remains controversial.
  
  
  RESULTS
  We studied systemic and coronary flow responses to the endothelium-dependent agonist, acetylcholine, the cGMP-dependent NO-donor, nitroglycerin, the predominantly endothelium-independent agonist, adenosine, the beta-adrenergic cAMP-dependent agonist, isoproterenol, and the calcium channel antagonist, nicardipine, in conscious dogs with pacing-induced DCM. Systemic blood flow response was impaired to acetylcholine but preserved to other vasodilators in DCM. In contrast, coronary blood flow response was significantly ( P < .05) depressed to all agonists. (Peak coronary blood flow response, control versus DCM: acetylcholine: 221 +/- 14% versus 156 +/- 11%; nitroglycerin: 220 +/- 17% versus 138 +/- 9%; adenosine: 635 +/- 65% versus 376 +/- 56%; nicardipine: 338 +/- 59% versus 115 +/- 23%; isoproterenol: 219 +/- 18% versus 86 +/- 20%). The attenuation was independent of systemic hemodynamic differences.
  
  
  CONCLUSIONS
  In contrast to systemic responses, coronary blood flow responses in DCM are impaired dependent or independent of NO or second messenger mechanisms, implying either distal signaling defects or structural abnormalities in the coronary vasculature.
authors.affiliation: Cardiovascular Research Institute and Department of Medicine, Allegheny General Hospital, 320 East North Avenue, Pittsburgh, PA 15212, USA.
authors.forename: Lazaros A
authors.initials: LA
authors.lastname: Nikolaidis
authors.forename: Michael A
authors.initials: MA
authors.lastname: Mathier
authors.forename: Aaron
authors.initials: A
authors.lastname: Doverspike
authors.forename: Teresa
authors.initials: T
authors.lastname: Hentosz
authors.forename: Rhonda
authors.initials: R
authors.lastname: Huerbin
authors.forename: Carol J
authors.initials: CJ
authors.lastname: Stolarski
authors.forename: Richard P
authors.initials: RP
authors.lastname: Shannon
mesh_terms: D000109:Acetylcholine / Q000494:pharmacology; D000241:Adenosine / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D002311:Cardiomyopathy, Dilated / Q000503:physiopathology*; D003326:Coronary Circulation / Q000187:drug effects / Q000502:physiology*; D004285:Dogs; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D045462:Endothelium-Dependent Relaxing Factors / Q000032:analysis / Q000502:physiology*; D007545:Isoproterenol / Q000494:pharmacology; D009529:Nicardipine / Q000494:pharmacology; D009569:Nitric Oxide / Q000032:analysis / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D005996:Nitroglycerin / Q000494:pharmacology; D014664:Vasodilation / Q000502:physiology; D014665:Vasodilator Agents / Q000494:pharmacology
chemical_list: D000318:Adrenergic beta-Agonists; D002121:Calcium Channel Blockers; D045462:Endothelium-Dependent Relaxing Factors; D020030:Nitric Oxide Donors; D014665:Vasodilator Agents; D009569:Nitric Oxide; D009529:Nicardipine; D005996:Nitroglycerin; D000241:Adenosine; D007545:Isoproterenol; D000109:Acetylcholine